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1.
Biomaterials ; 313: 122763, 2025 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-39180917

RESUMO

Cuproptosis is a new kind of cell death that depends on delivering copper ions into mitochondria to trigger the aggradation of tricarboxylic acid (TCA) cycle proteins and has been observed in various cancer cells. However, whether cuproptosis occurs in cancer stem cells (CSCs) is unexplored thus far, and CSCs often reside in a hypoxic tumor microenvironment (TME) of triple negative breast cancers (TNBC), which suppresses the expression of the cuproptosis protein FDX1, thereby diminishing anticancer efficacy of cuproptosis. Herein, a ROS-responsive active targeting cuproptosis-based nanomedicine CuET@PHF is developed by stabilizing copper ionophores CuET nanocrystals with polydopamine and hydroxyethyl starch to eradicate CSCs. By taking advantage of the photothermal effects of CuET@PHF, tumor hypoxia is overcome via tumor mechanics normalization, thereby leading to enhanced cuproptosis and immunogenic cell death in 4T1 CSCs. As a result, the integration of CuET@PHF and mild photothermal therapy not only significantly suppresses tumor growth but also effectively inhibits tumor recurrence and distant metastasis by eliminating CSCs and augmenting antitumor immune responses. This study presents the first evidence of cuproptosis in CSCs, reveals that disrupting hypoxia augments cuproptosis cancer therapy, and establishes a paradigm for potent cancer therapy by simultaneously eliminating CSCs and boosting antitumor immunity.


Assuntos
Cobre , Nanomedicina , Células-Tronco Neoplásicas , Neoplasias de Mama Triplo Negativas , Microambiente Tumoral , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/terapia , Microambiente Tumoral/efeitos dos fármacos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Animais , Feminino , Nanomedicina/métodos , Cobre/química , Cobre/farmacologia , Linhagem Celular Tumoral , Camundongos , Nanopartículas/química , Camundongos Endogâmicos BALB C , Terapia Fototérmica/métodos , Humanos , Polímeros/química , Indóis/farmacologia
2.
Biomaterials ; 313: 122771, 2025 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-39190940

RESUMO

The notorious tumor microenvironment (TME) usually becomes more deteriorative during phototherapeutic progress that hampers the antitumor efficacy. To overcome this issue, we herein report the ameliorative and adaptive nanoparticles (TPASIC-PFH@PLGA NPs) that simultaneously reverse hypoxia TME and switch photoactivities from photothermal-dominated state to photodynamic-dominated state to maximize phototherapeutic effect. TPASIC-PFH@PLGA NPs are designed by incorporating oxygen-rich liquid perfluorohexane (PFH) into the intraparticle microenvironment to regulate the intramolecular motions of AIE photosensitizer TPASIC. TPASIC exhibits a unique aggregation-enhanced reactive oxygen species (ROS) generation feature. PFH incorporation affords TPASIC the initially dispersed state, thus promoting active intramolecular motions and photothermal conversion efficiency. While PFH volatilization leads to nanoparticle collapse and the formation of tight TPASIC aggregates with largely enhanced ROS generation efficiency. As a consequence, PFH incorporation not only currently promotes both photothermal and photodynamic efficacies of TPASIC and increases the intratumoral oxygen level, but also enables the smart photothermal-to-photodynamic switch to maximize the phototherapeutic performance. The integration of PFH and AIE photosensitizer eventually delivers more excellent antitumor effect over conventional phototherapeutic agents with fixed photothermal and photodynamic efficacies. This study proposes a new nanoengineering strategy to ameliorate TME and adapt the treatment modality to fit the changed TME for advanced antitumor applications.


Assuntos
Fluorocarbonos , Nanopartículas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Espécies Reativas de Oxigênio , Microambiente Tumoral , Nanopartículas/química , Microambiente Tumoral/efeitos dos fármacos , Animais , Fotoquimioterapia/métodos , Espécies Reativas de Oxigênio/metabolismo , Fluorocarbonos/química , Fluorocarbonos/farmacologia , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Humanos , Camundongos , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Camundongos Endogâmicos BALB C , Terapia Fototérmica/métodos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Fototerapia/métodos , Feminino
3.
Biomaterials ; 312: 122724, 2025 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39106818

RESUMO

The residual bone tumor and defects which is caused by surgical therapy of bone tumor is a major and important problem in clinicals. And the sequential treatment for irradiating residual tumor and repairing bone defects has wildly prospects. In this study, we developed a general modification strategy by gallic acid (GA)-assisted coordination chemistry to prepare black calcium-based materials, which combines the sequential photothermal therapy of bone tumor and bone defects. The GA modification endows the materials remarkable photothermal properties. Under the near-infrared (NIR) irradiation with different power densities, the black GA-modified bone matrix (GBM) did not merely display an excellent performance in eliminating bone tumor with high temperature, but showed a facile effect of the mild-heat stimulation to accelerate bone regeneration. GBM can efficiently regulate the microenvironments of bone regeneration in a spatial-temporal manner, including inflammation/immune response, vascularization and osteogenic differentiation. Meanwhile, the integrin/PI3K/Akt signaling pathway of bone marrow mesenchymal stem cells (BMSCs) was revealed to be involved in the effect of osteogenesis induced by the mild-heat stimulation. The outcome of this study not only provides a serial of new multifunctional biomaterials, but also demonstrates a general strategy for designing novel blacked calcium-based biomaterials with great potential for clinical use.


Assuntos
Neoplasias Ósseas , Regeneração Óssea , Cálcio , Ácido Gálico , Células-Tronco Mesenquimais , Ácido Gálico/química , Regeneração Óssea/efeitos dos fármacos , Animais , Cálcio/metabolismo , Neoplasias Ósseas/terapia , Neoplasias Ósseas/tratamento farmacológico , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Terapia Fototérmica/métodos , Osteogênese/efeitos dos fármacos , Camundongos , Humanos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Linhagem Celular Tumoral
4.
Biomaterials ; 312: 122751, 2025 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39121726

RESUMO

Tumor immunotherapies have emerged as a promising frontier in the realm of cancer treatment. However, challenges persist in achieving localized, durable immunostimulation while counteracting the tumor's immunosuppressive environment. Here, we develop a natural mussel foot protein-based nanomedicine with spatiotemporal control for tumor immunotherapy. In this nanomedicine, an immunoadjuvant prodrug and a photosensitizer are integrated, which is driven by their dynamic bonding and non-covalent assembling with the protein carrier. Harnessing the protein carrier's bioadhesion, this nanomedicine achieves a drug co-delivery with spatiotemporal precision, by which it not only promotes tumor photothermal ablation but also broadens tumor antigen repertoire, facilitating in situ immunotherapy with durability and maintenance. This nanomedicine also modulates the tumor microenvironment to overcome immunosuppression, thereby amplifying antitumor responses against tumor progression. Our strategy underscores a mussel foot protein-derived design philosophy of drug delivery aimed at refining combinatorial immunotherapy, offering insights into leveraging natural proteins for cancer treatment.


Assuntos
Imunoterapia , Nanomedicina , Animais , Imunoterapia/métodos , Nanomedicina/métodos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Terapia Fototérmica/métodos , Camundongos , Humanos , Microambiente Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral , Proteínas/química , Feminino , Neoplasias/terapia , Neoplasias/imunologia , Adesivos/química , Camundongos Endogâmicos C57BL , Adjuvantes Imunológicos/farmacologia
5.
Biomaterials ; 312: 122739, 2025 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39096840

RESUMO

The biofilm-induced "relatively immune-compromised zone" creates an immunosuppressive microenvironment that is a significant contributor to refractory infections in orthopedic endophytes. Consequently, the manipulation of immune cells to co-inhibit or co-activate signaling represents a crucial strategy for the management of biofilm. This study reports the incorporation of Mn2+ into mesoporous dopamine nanoparticles (Mnp) containing the stimulator of interferon genes (STING) pathway activator cGAMP (Mncp), and outer wrapping by M1-like macrophage cell membrane (m-Mncp). The cell membrane enhances the material's targeting ability for biofilm, allowing it to accumulate locally at the infectious focus. Furthermore, m-Mncp mechanically disrupts the biofilm through photothermal therapy and induces antigen exposure through photodynamic therapy-generated reactive oxygen species (ROS). Importantly, the modulation of immunosuppression and immune activation results in the augmentation of antigen-presenting cells (APCs) and the commencement of antigen presentation, thereby inducing biofilm-specific humoral immunity and memory responses. Additionally, this approach effectively suppresses the activation of myeloid-derived suppressor cells (MDSCs) while simultaneously boosting the activity of T cells. Our study showcases the efficacy of utilizing m-Mncp immunotherapy in conjunction with photothermal and photodynamic therapy to effectively mitigate residual and recurrent infections following the extraction of infected implants. As such, this research presents a viable alternative to traditional antibiotic treatments for biofilm that are challenging to manage.


Assuntos
Biofilmes , Indóis , Proteínas de Membrana , Polímeros , Biofilmes/efeitos dos fármacos , Polímeros/química , Animais , Indóis/química , Indóis/farmacologia , Camundongos , Proteínas de Membrana/metabolismo , Nanopartículas/química , Fotoquimioterapia/métodos , Porosidade , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Feminino , Transdução de Sinais/efeitos dos fármacos , Terapia Fototérmica , Células Supressoras Mieloides/metabolismo , Células Supressoras Mieloides/efeitos dos fármacos , Camundongos Endogâmicos C57BL
6.
Biomaterials ; 313: 122794, 2025 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-39241552

RESUMO

Complex tissue damage accompanying with bacterial infection challenges healthcare systems globally. Conventional tissue engineering scaffolds normally generate secondary implantation trauma, mismatched regeneration and infection risks. Herein, we developed an easily implanted scaffold with multistep shape memory and photothermal-chemodynamic properties to exactly match repair requirements of each part from the tissue defect by adjusting its morphology as needed meanwhile inhibiting bacterial infection on demand. Specifically, a thermal-induced shape memory scaffold was prepared using hydroxyethyl methacrylate and polyethylene glycol diacrylate, which was further combined with the photothermal agent iron tannate (FeTA) to produce NIR light-induced shape memory property. By varying ingredients ratios in each segment, this scaffold could perform a stepwise recovery under different NIR periods. This process facilitated implantation after shape fixing to avoid trauma caused by conventional methods and gradually filled irregular defects under NIR to perform suitable tissue regeneration. Moreover, FeTA also catalyzed Fenton reaction at bacterial infections with abundant H2O2, which produced excess ROS for chemodynamic antibacterial therapy. As expected, bacteriostatic rate was further enhanced by additional photothermal therapy under NIR. The in vitro and vivo results showed that our scaffold was able to perform high efficacy in both antibiosis, inflammation reduction and wound healing acceleration, indicating a promising candidate for the regeneration of complex tissue damage with bacterial infection.


Assuntos
Antibacterianos , Alicerces Teciduais , Cicatrização , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/uso terapêutico , Animais , Alicerces Teciduais/química , Camundongos , Cicatrização/efeitos dos fármacos , Raios Infravermelhos , Terapia Fototérmica , Engenharia Tecidual/métodos , Taninos/química , Taninos/farmacologia , Materiais Inteligentes/química , Staphylococcus aureus/efeitos dos fármacos , Masculino , Polietilenoglicóis/química
7.
J Nanobiotechnology ; 22(1): 561, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39272205

RESUMO

BACKGROUND: T cell-based immunotherapies are facing great challenges in the recruitment and activation of tumor-specific T cells against solid tumors. Among which, utilizing nanobody (Nb) or nanobodies (Nbs) to construct T cell engager has emerged as a more practical potential for enhancing the anti-tumor effectiveness of T cells. Here, we designed a new Nb-guided multifunctional T cell engager (Nb-MuTE) that not only recruited effector T cells into the tumor tissues, but also efficiently activated T cells anti-tumor immunity when synergies with photothermal effect. RESULTS: The Nb-MuTE, which was constructed based on an indocyanine green (ICG)-containing liposome with surface conjugation of CD105 and CD3 Nbs, and showed excellent targetability to both tumor and T cells, following enhancement of activation, proliferation and cytokine secretion of tumor-specific T cells. Notably, the immunological anti-tumor functions of Nb-MuTE-mediated T cells were further enhanced by the ICG-induced photothermal effect in vitro and in vivo. CONCLUSIONS: Such a new platform Nb-MuTE provides a practical and "all-in-one" strategy to potentiate T cell responses for the treatment of solid tumor in clinic.


Assuntos
Imunoterapia , Verde de Indocianina , Anticorpos de Domínio Único , Linfócitos T , Animais , Anticorpos de Domínio Único/química , Anticorpos de Domínio Único/imunologia , Camundongos , Linfócitos T/imunologia , Verde de Indocianina/química , Imunoterapia/métodos , Linhagem Celular Tumoral , Humanos , Neoplasias/terapia , Neoplasias/imunologia , Feminino , Camundongos Endogâmicos BALB C , Terapia Fototérmica/métodos , Lipossomos/química , Ativação Linfocitária , Camundongos Endogâmicos C57BL , Complexo CD3/imunologia
8.
Int J Mol Sci ; 25(17)2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39273127

RESUMO

As a novel therapeutic approach, photothermal therapy (PTT) combined with chemotherapy can synergistically produce antitumor effects. Herein, dithiodipropionic acid (DTDP) was used as a donor of disulfide bonds sensitive to the tumor microenvironment for establishing chemical bonding between the photosensitizer indocyanine green amino (ICG-NH2) and acidified single-walled carbon nanotubes (CNTs). The CNT surface was then coated with conjugates (HD) formed by the targeted modifier hyaluronic acid (HA) and 1,2-tetragacylphosphatidyl ethanolamine (DMPE). After doxorubicin hydrochloride (DOX), used as the model drug, was loaded by CNT carriers, functional nano-delivery systems (HD/CNTs-SS-ICG@DOX) were developed. Nanosystems can effectively induce tumor cell (MCF-7) death in vitro by accelerating cell apoptosis, affecting cell cycle distribution and reactive oxygen species (ROS) production. The in vivo antitumor activity results in tumor-bearing model mice, further verifying that HD/CNTs-SS-ICG@DOX inhibited tumor growth most significantly by mediating a synergistic effect between chemotherapy and PTT, while various functional nanosystems have shown good biological tissue safety. In conclusion, the composite CNT delivery systems developed in this study possess the features of high biocompatibility, targeted delivery, and responsive drug release, and can achieve the efficient coordination of chemotherapy and PTT, with broad application prospects in cancer treatment.


Assuntos
Doxorrubicina , Nanotubos de Carbono , Terapia Fototérmica , Microambiente Tumoral , Nanotubos de Carbono/química , Animais , Humanos , Microambiente Tumoral/efeitos dos fármacos , Terapia Fototérmica/métodos , Camundongos , Doxorrubicina/farmacologia , Doxorrubicina/química , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Verde de Indocianina/química , Células MCF-7 , Espécies Reativas de Oxigênio/metabolismo , Apoptose/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Feminino , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Endogâmicos BALB C , Terapia Combinada/métodos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Antineoplásicos/administração & dosagem , Ácido Hialurônico/química
9.
Molecules ; 29(17)2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39274898

RESUMO

Multifunctional targeted drug delivery systems have been explored as a novel cancer treatment strategy to overcome limitations of traditional chemotherapy. The combination of photodynamic therapy and chemotherapy has been shown to enhance efficacy, but the phototoxicity of traditional photosensitizers is a challenge. In this study, we prepared a multi-sensitive composite hydrogel containing gold nanoclusters (Au NCs) and the temperature-sensitive antitumor drug 5-fluorourac il (5-FU) using carboxymethyl cellulose (Carr) as a dual-functional template. Au NCs were synthesized using sodium borohydride as a reducing agent and potassium as a promoter. The resulting Au NCs were embedded in the Carr hydrogel, which was then conjugated with lactobionic acid (LA) as a targeting ligand. The resulting Au NCs/5-FU@Carr-LA composite hydrogel was used for synergistic photodynamic therapy (PDT), photothermal therapy (PTT), and chemotherapy. Au NCs/5-FU@Carr-LA releases the drug faster at pH 5.0 due to the acid sensitivity of the Carr polymer chain. In addition, at 50 °C, the release rate of Au NCs/5-FU@Carr-LA is 78.2%, indicating that the higher temperature generated by the photothermal effect is conducive to the degradation of Carr polymer chains. The Carr hydrogel stabilized the Au NCs and acted as a matrix for drug loading, and the LA ligand facilitated targeted delivery to tumor cells. The composite hydrogel exhibited excellent biocompatibility and synergistic antitumor efficacy, as demonstrated by in vitro and in vivo experiments. In addition, the hydrogel had thermal imaging capabilities, making it a promising multifunctional platform for targeted cancer therapy.


Assuntos
Fluoruracila , Ouro , Hidrogéis , Nanopartículas Metálicas , Fotoquimioterapia , Ouro/química , Hidrogéis/química , Fluoruracila/farmacologia , Fluoruracila/química , Animais , Nanopartículas Metálicas/química , Camundongos , Humanos , Fotoquimioterapia/métodos , Antineoplásicos/farmacologia , Antineoplásicos/química , Sistemas de Liberação de Medicamentos , Linhagem Celular Tumoral , Carboximetilcelulose Sódica/química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Liberação Controlada de Fármacos , Terapia Fototérmica/métodos
10.
Colloids Surf B Biointerfaces ; 244: 114179, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39217727

RESUMO

Oral squamous cell carcinoma (OSCC) is highly heterogeneous and aggressive, but therapies based on single-targeted nanoparticles frequently address these tumors as a single illness. To achieve more efficient drug transport, it is crucial to develop nanodrug-carrying systems that simultaneously target two or more cancer biomarkers. In addition, combining chemotherapy with near-infrared (NIR) light-mediated thermotherapy allows the thermal ablation of local malignancies via photothermal therapy (PTT), and triggers drug release to improve chemosensitivity. Thus, a novel dual-targeted nano-loading system, DOX@GO-HA-HN-1 (GHHD), was created for synergistic chemotherapy and PTT by the co-modification of carboxylated graphene oxide (GO) with hyaluronic acid (HA) and HN-1 peptide and loading with the anticancer drug doxorubicin (DOX). Targeted delivery using GHHD was shown to be superior to single-targeted nanoparticle delivery. NIR radiation will encourage the absorption of GHHD by tumor cells and cause the site-specific release of DOX in conjunction with the acidic microenvironment of the tumor. In addition, chemo-photothermal combination therapy for cancer treatment was realized by causing cell apoptosis under the irradiation of 808-nm laser. In summary, the application of GHHD to chemotherapy combined with photothermal therapy for OSCC is shown to have important potential as a means of combatting the low accumulation of single chemotherapeutic agents in tumors and drug resistance generated by single therapeutic means, enhancing therapeutic efficacy.


Assuntos
Carcinoma de Células Escamosas , Doxorrubicina , Sistemas de Liberação de Medicamentos , Grafite , Raios Infravermelhos , Neoplasias Bucais , Doxorrubicina/farmacologia , Doxorrubicina/química , Humanos , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/patologia , Neoplasias Bucais/terapia , Grafite/química , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Concentração de Íons de Hidrogênio , Portadores de Fármacos/química , Nanopartículas/química , Liberação Controlada de Fármacos , Animais , Apoptose/efeitos dos fármacos , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/administração & dosagem , Proliferação de Células/efeitos dos fármacos , Terapia Fototérmica , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Ácido Hialurônico/química , Sobrevivência Celular/efeitos dos fármacos , Camundongos , Tamanho da Partícula , Propriedades de Superfície
11.
Int J Nanomedicine ; 19: 9597-9612, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39296938

RESUMO

Purpose: The chemotherapeutic agent doxorubicin (DOX) is limited by its cardiotoxicity, posing challenges in its application for non-small cell lung cancer (NSCLC). This study aims to explore the efficacy of polydopamine/Au nanoparticles loaded with DOX for chemotherapy and photothermal therapy in NSCLC to achieve enhanced efficacy and reduced toxicity. Methods: Hollow polydopamine (HPDA)/Au@DOX was synthesized via polydopamine chemical binding sacrificial template method. Morphology was characterized using transmission electron microscopy, particle size and potential were determined using dynamic light scattering, and photothermal conversion efficiency was assessed using near-infrared (NIR) thermal imaging. Drug loading rate and in vitro drug release were investigated. In vitro, anti-tumor experiments were conducted using CCK-8 assay, flow cytometry, and live/dead cell staining to evaluate the cytotoxicity of HPDA/Au@DOX on A549 cells. Uptake of HPDA/Au@DOX by A549 cells was detected using the intrinsic fluorescence of DOX. The in vivo anti-metastasis and anti-tumor effects of HPDA/Au@DOX were explored in mouse lung metastasis and subcutaneous tumor models, respectively. Results: HPDA/Au@DOX with a particle size of (164.26±3.25) nm, a drug loading rate of 36.31%, and an encapsulation efficiency of 90.78% was successfully prepared. Under 808 nm laser irradiation, HPDA/Au@DOX accelerated DOX release and enhanced uptake by A549 cells. In vitro photothermal performance assessment showed excellent photothermal conversion capability and stability of HPDA/Au@DOX under NIR laser irradiation. Both in vitro and in vivo experiments demonstrated that the photothermal-chemotherapy combination group (HPDA/Au@DOX+NIR) exhibited stronger anti-metastatic and anti-tumor activities compared to the monotherapy group (DOX). Conclusion: HPDA/Au@DOX nanosystem demonstrated excellent photothermal effect, inhibiting the growth and metastasis of A549 cells. This nanosystem achieves the combined effect of chemotherapy and photothermal, making it promising for NSCLC treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Doxorrubicina , Ouro , Indóis , Neoplasias Pulmonares , Nanosferas , Terapia Fototérmica , Polímeros , Indóis/química , Indóis/farmacologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Animais , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacocinética , Polímeros/química , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Células A549 , Ouro/química , Terapia Fototérmica/métodos , Camundongos , Nanosferas/química , Liberação Controlada de Fármacos , Camundongos Nus , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Ensaios Antitumorais Modelo de Xenoenxerto , Terapia Combinada/métodos , Sobrevivência Celular/efeitos dos fármacos , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/administração & dosagem
12.
Int J Nanomedicine ; 19: 9689-9705, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39309187

RESUMO

Background: Epidermal growth factor receptor (EGFR) is a major target for the treatment of colorectal cancer. Thus, anti-EGFR antibody conjugated lipid-polymer hybrid nanoparticles can offer a potential means of enhancing the efficacy of chemotherapeutics in EGFR overexpressing cancers. In addition, the combination of chemotherapy and photothermal therapy is a promising strategy for cancer treatment. Hence, it is highly desirable to develop a safe and effective delivery system for colorectal tumor therapy. Methods: In this study, EGFR-targeted and NIR-triggered lipid-polymer hybrid nanoparticles (abbreviated as Cet-Iri-NPs) were prepared with copolymer PPG-PEG, lipids DSPE-PEG-Mal and lecithin as carriers, CPT-11 as an anticancer chemotherapeutic agent, indocyanine green (ICG) as a photothermal agent, and cetuximab as a surface-targeting ligand. Results: In vitro analyses revealed that Cet-Iri-NPs were spherical with size of 99.88 nm, charge of 29.17 mV, drug entrapment efficiency of 51.72%, and antibody conjugation efficiency of 41.70%. Meanwhile, Cet-Iri-NPs exhibited a remarkable photothermal effect, and pH/NIR-triggered faster release of CPT-11 with near infrared (NIR) laser irradiation, which induced enhanced cytotoxicity against SW480 cells. Furthermore, the promoted tumor-growth suppression effect of Cet-Iri-NPs on SW480 tumor xenograft nude mice was achieved under NIR laser irradiation. Conclusion: These results indicate that the well-defined Cet-Iri-NPs are a promising platform for targeted colorectal cancer treatment with chemo-photothermal therapy.


Assuntos
Cetuximab , Neoplasias Colorretais , Receptores ErbB , Verde de Indocianina , Irinotecano , Nanopartículas , Terapia Fototérmica , Receptores ErbB/metabolismo , Neoplasias Colorretais/terapia , Neoplasias Colorretais/tratamento farmacológico , Animais , Humanos , Irinotecano/farmacologia , Irinotecano/química , Irinotecano/farmacocinética , Irinotecano/administração & dosagem , Linhagem Celular Tumoral , Nanopartículas/química , Cetuximab/química , Cetuximab/farmacologia , Cetuximab/farmacocinética , Terapia Fototérmica/métodos , Verde de Indocianina/química , Verde de Indocianina/farmacocinética , Verde de Indocianina/farmacologia , Verde de Indocianina/administração & dosagem , Camundongos , Camundongos Nus , Polietilenoglicóis/química , Camundongos Endogâmicos BALB C , Camptotecina/química , Camptotecina/farmacologia , Camptotecina/farmacocinética , Camptotecina/administração & dosagem , Portadores de Fármacos/química , Polímeros/química , Raios Infravermelhos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Lecitinas/química , Ensaios Antitumorais Modelo de Xenoenxerto , Lipídeos/química
13.
Theranostics ; 14(14): 5608-5620, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39310104

RESUMO

Background: Current anti-obesity medications suffer from limited efficacy and side-effects because they act indirectly on either the central nervous system or gastrointestinal system. Herein, this work aims to introduce a transdermal photothermal and nanocatalytic therapy enabled by Prussian blue nanoparticles, which directly act on obese subcutaneous white adipose tissue (sWAT) to induce its beneficial remodeling including stimulation of browning, lipolysis, secretion of adiponectin, as well as reduction of oxidative stress, hypoxia, and inflammation. Methods: Prussian blue nanoparticles were synthesized and incorporated into silk fibroin hydrogel for sustained retention. The efficacy of mild photothermal (808 nm, 0.4 W/cm2, 5 min) and nanocatalytic therapy (mPTT-NCT) was assessed both in vitro (3T3-L1 adipocytes) and in vivo (obese mice). The underlying signaling pathways are carefully revealed. Additionally, biosafety studies were conducted to further validate the potential of this therapy for practical application. Results: On 3T3-L1 adipocytes, mPTT-NCT was able to induce browning, enhance lipolysis, and alleviate oxidative stress. On obese mice model, the synergistic treatment led to not only large mass reduction of the targeted sWAT (53.95%) but also significant improvement of whole-body metabolism as evidenced by the substantial decrease of visceral fat (65.37%), body weight (9.78%), hyperlipidemia, and systemic inflammation, as well as total relief of type 2 diabetes. Conclusions: By directly targeting obese sWAT to induce its beneficial remodeling, this synergistic therapy leads to significant improvements in whole-body metabolism and the alleviation of obesity-related conditions, including type 2 diabetes. The elucidation of underlying signaling pathways provides fundamental insights and shall inspire new strategies to combat obesity and its associated diseases.


Assuntos
Células 3T3-L1 , Ferrocianetos , Nanopartículas , Obesidade , Animais , Camundongos , Obesidade/terapia , Nanopartículas/química , Ferrocianetos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Masculino , Terapia Fototérmica/métodos , Camundongos Endogâmicos C57BL , Adipócitos/metabolismo , Camundongos Obesos , Lipólise/efeitos dos fármacos , Modelos Animais de Doenças , Tecido Adiposo Branco/metabolismo
14.
Biochemistry (Mosc) ; 89(8): 1362-1391, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39245451

RESUMO

The review summarises the prospects in the application of graphene and graphene-based nanomaterials (GBNs) in nanomedicine, including drug delivery, photothermal and photodynamic therapy, and theranostics in cancer treatment. The application of GBNs in various areas of science and medicine is due to the unique properties of graphene allowing the development of novel ground-breaking biomedical applications. The review describes current approaches to the production of new targeting graphene-based biomedical agents for the chemotherapy, photothermal therapy, and photodynamic therapy of tumors. Analysis of publications and FDA databases showed that despite numerous clinical studies of graphene-based materials conducted worldwide, there is a lack of information on the clinical trials on the use of graphene-based conjugates for the targeted drug delivery and diagnostics. The review will be helpful for researchers working in development of carbon nanostructures, material science, medicinal chemistry, and nanobiomedicine.


Assuntos
Grafite , Neoplasias , Nanomedicina Teranóstica , Grafite/química , Grafite/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Nanomedicina Teranóstica/métodos , Fotoquimioterapia , Nanoestruturas/uso terapêutico , Nanoestruturas/química , Sistemas de Liberação de Medicamentos , Animais , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Terapia Fototérmica/métodos
15.
Int J Nanomedicine ; 19: 8901-8927, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39233743

RESUMO

Introduction: Graphene oxide (GO) nanoparticles have emerged as a compelling photothermal agent (PHTA) in the realm of photothermal antibacterial therapy, owing to their cost-effectiveness, facile synthesis, and remarkable photostability. Nevertheless, the therapeutic efficacy of GO nanoparticles is commonly hindered by their inherent drawback of low photothermal conversion efficiency (PCE). Methods: Herein, we engineer the Ag/GO-GelMA platform by growing the Ag on the surface of GO and encapsulating the Ag/GO nanoparticles into the GelMA hydrogels. Results: The resulting Ag/GO-GelMA platform demonstrates a significantly enhanced PCE (47.6%), surpassing that of pure GO (11.8%) by more than fourfold. As expected, the Ag/GO-GelMA platform, which was designed to integrate the benefits of Ag/GO nanoparticles (high PCE) and hydrogel (slowly releasing Ag+ to exert an inherent antibacterial effect), has been shown to exhibit exceptional antibacterial efficacy. Furthermore, transcriptome analyses demonstrated that the Ag/GO-GelMA platform could significantly down-regulate pathways linked to inflammation (the MAPK and PI3K-Akt pathways) and had the ability to promote cell migration. Discussion: Taken together, this study presents the design of a potent photothermal antibacterial platform (Ag/GO-GelMA) aimed at enhancing the healing of infectious wounds. The platform utilizes a handy method to enhance the PCE of GO, thereby making notable progress in the utilization of GO nano-PHTAs.


Assuntos
Antibacterianos , Grafite , Hidrogéis , Prata , Cicatrização , Grafite/química , Grafite/farmacologia , Cicatrização/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Prata/química , Prata/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Humanos , Camundongos , Terapia Fototérmica/métodos , Nanopartículas/química , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos
16.
Theranostics ; 14(13): 4933-4947, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39267783

RESUMO

Rationale: Optogenetically engineered facultative anaerobic bacteria exhibit a favorable tendency to colonize at solid tumor sites and spatiotemporally-programmable therapeutics release abilities, attracting extensive attention in precision tumor therapy. However, their therapeutic efficacy is moderate. Conventional photothermal agents with high tumor ablation capabilities exhibit low tumor targeting efficiency, resulting in significant off-target side effects. The combination of optogenetics and photothermal therapy may offer both tumor-targeting and excellent tumor-elimination capabilities, which unfortunately has rarely been investigated. Herein, we construct a bacteria-based cascade near-infrared optogentical-photothermal system (EcNαHL-UCNPs) for enhanced tumor therapy. Methods: EcNαHL-UCNPs consists of an optogenetically engineered Escherichia coli Nissle 1917 (EcN) conjugated with lanthanide-doped upconversion nanoparticles (UCNPs), which are capable of locally secreting α-hemolysin (αHL), a pore-forming protein, in responsive to NIR irradiation. Anti-tumor effects of EcNαHL-UCNPs were determined in both H22 and 4T1 tumors. Results: The αHL not only eliminates tumor cells, but more importantly disrupts endothelium to form thrombosis as an in situ photothermal agent in tumors. The in situ formed thrombosis significantly potentiates the photothermic ablation of H22 tumors upon subsequent NIR light irradiation. Besides, αHL secreted by EcNαHL-UCNPs under NIR light irradiation not only inhibits 4T1 tumor growth, but also suppresses metastasis of 4T1 tumor via inducing the immune response. Conclusion: Our studies highlight bacteria-based cascade optogenetical-photothermal system for precise and effective tumor therapy.


Assuntos
Escherichia coli , Nanopartículas , Optogenética , Terapia Fototérmica , Animais , Camundongos , Terapia Fototérmica/métodos , Escherichia coli/genética , Linhagem Celular Tumoral , Nanopartículas/química , Optogenética/métodos , Camundongos Endogâmicos BALB C , Raios Infravermelhos , Feminino , Neoplasias/terapia , Humanos , Fototerapia/métodos
17.
Carbohydr Polym ; 345: 122569, 2024 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-39227105

RESUMO

Breast cancer is a malignant tumor that poses a significant threat to women's health and single therapy fails to play a good oncological therapeutic effect. Synergistic treatment with multiple strategies may make up for the deficiencies and has gained widespread attention. In this study, sulfhydryl-modified hyaluronic acid (HA-SH) was covalently crosslinked with polydopamine (PDA) via a Michael addition reaction to develop an injectable hydrogel, in which PDA can be used not only as a matrix but also as a photothermal agent. After HSA and paclitaxel were spontaneously organized into nanoparticles via hydrophobic interaction, hyaluronic acid with low molecular weight was covalently linked to HSA, thus conferring effectively delivery. This photothermal injectable hydrogel incorporates PTX@HSA-HA nanoparticles, thereby initiating a thermochemotherapeutic response to target malignancy. Our results demonstrated that this injectable hydrogel possesses consistent drug delivery capability in a murine breast cancer model, collaborating with photothermal therapy to effectively suppress tumor growth, represented by low expression of Ki-67 and increasing apoptosis. Photothermal therapy (PTT) can effectively stimulate immune response by increasing IL-6 and TNF-α. Notably, the treatment did not elicit any indications of toxicity. This injectable hydrogel holds significant promise as a multifaceted therapeutic agent that integrates photothermal and chemotherapeutic modalities.


Assuntos
Neoplasias da Mama , Ácido Hialurônico , Hidrogéis , Paclitaxel , Terapia Fototérmica , Animais , Ácido Hialurônico/química , Hidrogéis/química , Hidrogéis/farmacologia , Feminino , Neoplasias da Mama/terapia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Camundongos , Terapia Fototérmica/métodos , Paclitaxel/farmacologia , Paclitaxel/química , Paclitaxel/administração & dosagem , Humanos , Indóis/química , Indóis/farmacologia , Camundongos Endogâmicos BALB C , Polímeros/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Nanopartículas/química , Portadores de Fármacos/química , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Fototerapia/métodos
18.
Carbohydr Polym ; 345: 122568, 2024 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-39227122

RESUMO

Bleeding and bacterial infection are common problems associated with wound treatment, while effective blood clotting and vessel regeneration promotion are the primary considerations to design the wound dressing materials. This research presents a chitosan-based hydrogel with grafted quaternary ammonium and polyphosphate (QCSP hydrogel) as the antibacterial hemostatic dressing to achieve burn wound treatment. The tissue adhesion of the hydrogel sealed the blood flow and the polyphosphate grafted to the chitosan promoted the activation of coagulation factor V to enhance the hemostasis. At the same time, the grafted quaternary ammonium enhanced the antibacterial ability of the biodegradable hydrogel wound dressing. In addition, the polydopamine as a photothermal agent was composited into the hydrogel to enhance the antibacterial and reactive oxygen scavenging performance. The in vivo hemostasis experiment proved the polyphosphate enhanced the coagulation property. Moreover, this photothermal property of the composite hydrogel enhanced the burn wound repairing rate combined with the NIR stimulus. As a result, this hydrogel could have potential application in clinic as dressing material for hemostasis and infection prone would repairing.


Assuntos
Antibacterianos , Queimaduras , Quitosana , Hemostasia , Hidrogéis , Indóis , Polímeros , Cicatrização , Quitosana/química , Quitosana/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Queimaduras/tratamento farmacológico , Queimaduras/terapia , Polímeros/química , Polímeros/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Animais , Indóis/química , Indóis/farmacologia , Cicatrização/efeitos dos fármacos , Hemostasia/efeitos dos fármacos , Camundongos , Hemostáticos/química , Hemostáticos/farmacologia , Bandagens , Masculino , Ratos , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Ratos Sprague-Dawley , Testes de Sensibilidade Microbiana , Terapia Fototérmica/métodos
19.
ACS Appl Mater Interfaces ; 16(37): 49114-49123, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39241120

RESUMO

Adjusting the catalytic activity of nanozymes for enhanced oncotherapy has attracted significant interest. However, it remains challenging to engineer regulatory tactics with a minimal impact on normal tissues. By exploiting the advantages of energy storage, photostimulated, and long afterglow luminescence of persistent nanoparticles (PLNPs), a persistent luminescence-based nanoreservoir was produced to improve its catalytic activity for benign oncotherapy. In the study, PLNPs in a nanoreservoir with the ability to store photons served as a self-illuminant to promote its peroxidase-like activity and therapeutic efficacy by persistently motivating its photothermal effect before and after external irradiation ceased. The photostimulated and persistent luminescence of PLNPs and spatiotemporal controllability of exogenous light jointly alleviated adverse effects induced by prolonged irradiation and elevated the catalytic capability of the nanoreservoir. Ultimately, the system fulfilled benign photothermal-intensive nanozymatic therapy. This work provides new insights into boosting the catalytic activity of nanozymes for secure disease treatment.


Assuntos
Luminescência , Nanopartículas , Nanopartículas/química , Nanopartículas/uso terapêutico , Humanos , Animais , Camundongos , Terapia Fototérmica , Catálise , Fototerapia , Neoplasias/terapia , Linhagem Celular Tumoral
20.
ACS Appl Mater Interfaces ; 16(37): 49083-49091, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39228328

RESUMO

Photothermal therapy (PTT) and photodynamic therapy (PDT) provide targeted approaches to cancer treatment, but each therapy has inherent limitations such as insufficient tissue penetration, uneven heat distribution, extreme hypoxia, and overexpressed HSP90 in tumor cells. To address these issues, herein, by encapsulating the IR780 dye and glucose oxidase (GOx) enzyme within ZIF-8 nanoparticles, we created a versatile system capable of combining photodynamic and enhanced photothermal therapy. The integration of the IR780 dye facilitated the generation of reactive oxygen species and hyperthermia upon light activation, enabling dual-mode cancer cell ablation. Moreover, GOx catalyzes the decomposition of glucose into gluconic acid and hydrogen peroxide, leading to the inhibition of ATP production and downregulation of heat shock protein 90 (HSP90) expression, sensitizing cancer cells to heat-induced cytotoxicity. This synergistic combination resulted in significantly improved therapeutic outcomes. Both in vitro and in vivo results validated that the nanoplatform demonstrated superior specificity and favorable therapeutic responses. Our innovative approach represents a promising strategy for overcoming current limitations in cancer treatments and offers the potential for clinical translation in the future.


Assuntos
Glucose Oxidase , Estruturas Metalorgânicas , Fotoquimioterapia , Terapia Fototérmica , Glucose Oxidase/química , Glucose Oxidase/metabolismo , Humanos , Animais , Camundongos , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Estruturas Metalorgânicas/síntese química , Concentração de Íons de Hidrogênio , Indóis/química , Indóis/farmacologia , Linhagem Celular Tumoral , Nanopartículas/química , Camundongos Endogâmicos BALB C , Espécies Reativas de Oxigênio/metabolismo , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Neoplasias/patologia , Camundongos Nus , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Imidazóis
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