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1.
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
2.
Biomaterials ; 313: 122761, 2025 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-39241550

RESUMO

Biofilm-associated infections (BAIs) continue to pose a major challenge in the medical field. Nanomedicine, in particular, promises significant advances in combating BAIs through the introduction of a variety of nanomaterials and nano-antimicrobial strategies. However, studies to date have primarily focused on the removal of the bacterial biofilm and neglect the subsequent post-biofilm therapeutic measures for BAIs, rendering pure anti-biofilm strategies insufficient for the holistic recovery of affected patients. Herein, we construct an emerging dual-functional composite nanosheet (SiHx@Ga) that responds to pHs fluctuation in the biofilm microenvironment to enable a sequential therapy of BAIs. In the acidic environment of biofilm, SiHx@Ga employs the self-sensitized photothermal Trojan horse strategy to effectively impair the reactive oxygen species (ROS) defense system while triggering oxidative stress and lipid peroxidation of bacteria, engendering potent antibacterial and anti-biofilm effects. Surprisingly, in the post-treatment phase, SiHx@Ga adsorbs free pathogenic nucleic acids released after biofilm destruction, generates hydrogen with ROS-scavenging and promotes macrophage polarization to the M2 type, effectively mitigating damaging inflammatory burst and promoting tissue healing. This well-orchestrated strategy provides a sequential therapy of BAIs by utilizing microenvironmental variations, offering a conceptual paradigm shift in the field of nanomedicine anti-infectives.


Assuntos
Antibacterianos , Biofilmes , Gálio , Espécies Reativas de Oxigênio , Biofilmes/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Gálio/química , Gálio/farmacologia , Camundongos , Portadores de Fármacos/química , Células RAW 264.7 , Humanos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia
3.
Int J Biol Macromol ; 279(Pt 4): 135479, 2024 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-39255880

RESUMO

Keratitis is the leading cause of blindness worldwide. In refractory cases, it can even lead to eyeball enucleation. The critical challenges of refractory keratitis are the drug-resistant bacteria and bacterial biofilms formation. Therefore, we established an innovative therapeutic approach for keratitis based on mild photothermal loop (MPL) therapy. First, we analyzed the bactericidal effect of methicillin-resistant Staphylococcus aureus (MRSA) under various loops and temperature durations to determine the optimal condition. Then, RAN-seq was applied to explore the underlying mechanisms. Additionally, we formulated a dual-purpose polyvinyl alcohol-polydopamine (PDA/PVA) hydrogel system and explored its effects on the reactive oxygen species (ROS) scavenging capability, antibacterial properties, and anti-inflammatory properties in vitro, as well as its effect in vivo. The results indicated substantial bactericidal properties after exposure in four loops, each lasting 10 min at 45 °C. RNA-seq revealed the altered genes related to virulence and biofilm formation. In addition to good photothermal performance, the PDA/PVA system could effectively eliminate MRSA, reduce ROS, inhibit biofilm formation, and decrease inflammatory factors expression. Moreover, the in vivo results demonstrated the potential of MPL for bacterial keratitis. This study serves as the first attempt to use MPL therapy for refractory keratitis, offering a new approach for clinical practice.

4.
Angew Chem Int Ed Engl ; : e202414879, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39325096

RESUMO

Mild photothermal therapy (MPTT) has emerged as a promising therapeutic modality for attenuating thermal damage to the normal tissues surrounding tumors, while the heat-induced upregulation of heat shock proteins (HSPs) greatly compromises the curative efficacy of MPTT by increasing cellular thermo-tolerance. Ferroptosis has been identified to suppress the overexpression of HSPs by the accumulation of lipid peroxides and reactive oxygen species (ROS), but is greatly restricted by overexpressed glutathione (GSH) in tumor microenvironment and undesirable ROS generation efficiency. Herein, a synergistic strategy based on the mutual enhancement of MPTT and ferroptosis is proposed for cleaving HSPs to recover tumor cell sensitivity. A facile method for fabricating a series of Fe-based metal-quinone networks (MQNs) by coordinated assembly is proposed and the representative FTP MQNs possess high photothermal conversion efficiency (69.3%). Upon 808 nm laser irradiation, FTP MQNs not only trigger effective MPTT to induce apoptosis but more significantly, potentiate Fenton reaction and marked GSH consumption to boost ferroptosis, and the reinforced ferroptosis effect in turn can alleviate the thermal resistance by declining the HSP70 defense and reducing ATP levels. This study provides a valuable rationale for constructing a large library of MQNs for achieving mutual enhancement of MPTT and ferroptosis.

5.
J Control Release ; 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39332776

RESUMO

Ferroptosis primarily relies on reactive oxygen (ROS) production and lipid peroxide (LPO) accumulation, which opens up new opportunities for tumor therapy. However, a standalone ferroptosis process is insufficient in inhibiting tumor progression. Unlike previously reported Fe-based nanomaterials, we have engineered a novel nanoreactor named IR780/Ce@EGCG/APT, which uses metal-polyphenols network (Ce@EGCG) based on rare-earth cerium and epigallocatechin gallate (EGCG) to encapsulate IR780 and modified with the aptamer (AS1411). The intricately designed nanoreactor is specifically taken up by tumor cells, releasing Ce3+, EGCG, and IR780. On the one hand, Ce3+ triggers ROS production via a Fenton-like reaction, inducing ferroptosis in tumor cells. On the other hand, IR780 accumulates in mitochondria and disrupts mitochondrial function upon laser irradiation, leading to tumor cell apoptosis. EGCG serves as a sensitizer, simultaneously enhancing the sensitivity of tumor cells to ferroptosis and photothermal therapy. After a single dose and three times of 808 nm laser irradiation for treatment, it has been observed that the nanoreactor induces dendritic cells (DCs) maturation, facilitates cytotoxic T lymphocyte infiltration, improves immunosuppressive microenvironment, activates the systemic immune system, and generates long-term immune memory.

6.
ACS Appl Mater Interfaces ; 16(38): 50335-50343, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39264146

RESUMO

Near-infrared (NIR) organic materials have been widely developed for tumor phototherapy due to their deep tumor penetration, good biodegradability, and high photothermal conversion (PCE). However, most of the NIR organic dyes are easily destroyed by photooxidation due to their big and long conjugated structures, such as cyanine dyes. Under light irradiation, the reactive oxygen species (ROS) produced by these NIR dyes can easily break their conjugated skeleton, resulting in a dramatic decrease in phototherapeutic efficiency. Herein, an NIR organic dye cyanine dye (CyS) and a photosensitizer methylene blue (MB) were chosen to prepare nanocarrier CMTNPs by facile self-assembling with a natural antioxidant, tannic acid (TA). TA can greatly enhance the stability of NIR cyanine dyes by scavenging ROS. Furthermore, CMTNPs have a character of pH/thermal dual response, allowing for controlled release of MB in the slightly acidic tumor environment during photothermal therapy. The released MB can turn on both fluorescence and photodynamic therapy effects. In vitro and in vivo experiments demonstrated the remarkable tumor ablation ability of CMTNPs. Thus, our study provided an antiphotobleaching and controlled release photosensitizer strategy through the introduction of antioxidant TA into the nanocarrier for efficient collaborative photothermal/photodynamic therapy.


Assuntos
Raios Infravermelhos , Azul de Metileno , Nanopartículas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Taninos , Taninos/química , Taninos/farmacologia , Animais , Camundongos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Humanos , Nanopartículas/química , Azul de Metileno/química , Azul de Metileno/farmacologia , Terapia Fototérmica , Portadores de Fármacos/química , Espécies Reativas de Oxigênio/metabolismo , Camundongos Endogâmicos BALB C , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Neoplasias/patologia , Linhagem Celular Tumoral , Polifenóis
7.
ACS Appl Mater Interfaces ; 16(38): 50369-50388, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39264653

RESUMO

Infectious bone defects resulting from surgery, infection, or trauma are a prevalent clinical issue. Current treatments commonly used include systemic antibiotics and autografts or allografts. Nevertheless, therapies come with various disadvantages, including multidrug-resistant bacteria, complications arising from the donor site, and immune rejection, which makes artificial implants desirable. However, artificial implants can fail due to bacterial infections and inadequate bone fusion after implantation. Thus, the development of multifunctional bone substitutes that are biocompatible, antibacterial, osteoconductive, and osteoinductive would be of great clinical importance. This study designs and prepares 2D graphene oxide (GO) and black phosphorus (BP) reinforced porous collagen (Col) scaffolds as a viable strategy for treating infectious bone defects. The fabricated Col-GO@BP scaffold exhibited an efficient photothermal antibacterial effect under near-infrared (NIR) irradiation. A further benefit of the NIR-controlled degradation of BP was to promote biomineralization by phosphorus-driven and calcium-extracted phosphorus in situ. The abundant functional groups in GO could synergistically capture the ions and enhance the in situ biomineralization. The Col-GO@BP scaffold facilitated osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSC) by leveraging its mild photothermal effect and biomineralization process, which upregulated heat shock proteins (HSPs) and activated PI3K/Akt pathways. Additionally, systematic in vivo experiments demonstrated that the Col-GO@BP scaffold obviously promotes infectious bone repair through admirable photothermal antibacterial performance and enhanced vascularization. As a result of this study, we provide new insights into the photothermal activity of GO@BP nanosheets, their degradation, and a new biological application for them.


Assuntos
Antibacterianos , Colágeno , Grafite , Células-Tronco Mesenquimais , Fosfatidilinositol 3-Quinases , Fósforo , Proteínas Proto-Oncogênicas c-akt , Alicerces Teciduais , Grafite/química , Grafite/farmacologia , Fósforo/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Fosfatidilinositol 3-Quinases/metabolismo , Colágeno/química , Alicerces Teciduais/química , Antibacterianos/química , Antibacterianos/farmacologia , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Raios Infravermelhos , Staphylococcus aureus/efeitos dos fármacos , Biomineralização/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Regeneração Óssea/efeitos dos fármacos , Ratos , Escherichia coli/efeitos dos fármacos
8.
ACS Appl Mater Interfaces ; 16(38): 51480-51495, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39287360

RESUMO

The challenge of drug-resistant bacteria-induced wound healing in clinical and public healthcare settings is significant due to the negative impacts on surrounding tissues and difficulties in monitoring the healing progress. We developed photothermal antibacterial nanorods (AuNRs-PU) with the aim of selectively targeting and combating drug-resistant Pseudomonas aeruginosa (P. aeruginosa). The AuNRs-PU were engineered with a bacterial-specific targeting polypeptide (UBI29-41) and a bacterial adhesive carbohydrate polymer composed of galactose and phenylboronic acid. The objective was to facilitate sutureless wound closure by specially distinguishing between bacteria and nontarget cells and subsequently employing photothermal methods to eradicate the bacteria. AuNRs-PU demonstrated high photothermal conversion efficiency in 808 nm laser and effectively caused physical harm to drug-resistant P. aeruginosa. By integrating the multifunctional bacterial targeting copolymer onto AuNRs, AuNRs-PU showed rapid and efficient bacterial targeting and aggregation in the presence of bacteria and cells, consequently shielding cells from bacterial harm. In a diabetic rat wound model, AuNRs-PU played a crucial role in enhancing healing by markedly decreasing inflammation and expediting epidermis formation, collagen deposition, and neovascularization levels. Consequently, the multifunctional photothermal therapy shows promise in addressing the complexities associated with managing drug-resistant infected wound healing.


Assuntos
Antibacterianos , Nanotubos , Terapia Fototérmica , Pseudomonas aeruginosa , Cicatrização , Animais , Cicatrização/efeitos dos fármacos , Nanotubos/química , Ratos , Antibacterianos/química , Antibacterianos/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos , Ratos Sprague-Dawley , Diabetes Mellitus Experimental/tratamento farmacológico , Humanos , Ácidos Borônicos/química , Ácidos Borônicos/farmacologia , Masculino
9.
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
10.
J Colloid Interface Sci ; 678(Pt C): 272-282, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39298978

RESUMO

Cancer immunotherapy has emerged as a potent treatment strategy by harnessing the host immune system to target cancer cells. However, challenges including low tumor vaccine immunogenicity and tumor heterogeneity hinder its clinical efficacy. To address these issues, we propose a novel nanoplatform integrating photothermal material gold nanorods (GNRs) with polyphenols for enhanced immunotherapy efficacy via photothermal therapy. Polyphenols, natural compounds with phenolic hydroxyl groups, are known for their ability to bind tightly to various molecules, making them ideal for antigen capture. We synthesized GNRs modified with polyphenols (GNR-PA and GNR-GA) and demonstrated their ability to induce immunogenic cell death upon laser irradiation, releasing tumor-associated antigens (TAAs). The surface polyphenols on GNRs effectively captured released TAAs to shield them from clearance. In vivo studies confirmed increased accumulation of GNR-GA in lymph nodes and enhanced dendritic cell maturation, leading to promoted effector T cell infiltration into tumors. Furthermore, treatment combined with PD-1/PD-L1 pathway blockade demonstrated potent tumor regression and systemic immunotherapy efficacy. Our findings highlight the potential of this photothermal nanoplatform as a promising strategy to overcome the limitations of current cancer immunotherapy approaches and improve therapeutic outcomes.

11.
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
12.
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
13.
J Colloid Interface Sci ; 678(Pt C): 796-803, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39312868

RESUMO

Chemodynamic therapy (CDT) and photothermal therapy (PTT) have both demonstrated considerable efficacy in the tumor treatment individually, owing to their non-invasive nature and excellent selectivity. However, due to the propensity of tumors for metastasis and recurrence, a singular therapeutic approach falls short of achieving optimal treatment outcomes. Polydopamine (PDA) has excellent photothermal conversion ability and polyoxometalates (POMs) possess diverse enzymatic activities. Here, we synthesized PDA@POM nanospheres comprising polydopamine-coated Tungsten-based polyoxometalate (W-POM). These nanospheres leverage dual enzymatic activities that synergistically enhance both chemodynamic and photothermal therapies for tumor treatment. The PDA-mediated PTT effect enables precise tumor cell destruction, while the W-POM nanozymes catalyzes the generation of highly toxic reactive oxygen species (ROS) from hydrogen peroxide within tumor cells through a Fenton-like reaction, which mitigates tumor hypoxia and induces tumor cell death. This synergistic photothermal catalytic therapy shows enhanced efficacy in tumor suppression, providing a promising new approach for tumor treatment.

14.
Mater Today Bio ; 28: 101232, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39315396

RESUMO

Tuberculosis (TB) remains the leading cause of deaths among infectious diseases worldwide. Cutaneous Tuberculosis (CTB), caused by Mycobacterium tuberculosis (Mtb) infection in the skin, is still a harmful public health issue that requires more effective treatment strategy. Herein, we introduced mannose-modified mesoporous polydopamine nanosystems (Man-mPDA NPs) as the macrophage-targeted vectors to deliver anti-TB drug rifampicin and as photothermal agent to facilitate photothermal therapy (PTT) against Mtb infected macrophages for synergistic treatment of CTB. Based on the selective macrophage targeting effects, the proposed Rif@Man-mPDA NPs also showed excellent photothermal properties to develop Rif@Man-mPDA NPs-mediated PTT for intracellular Mtb killings in macrophages. Importantly, Rif@Man-mPDA NPs could inhibit the immune escape of Mtb by effectively chelating intracellular Fe2+ and inhibiting lipid peroxidation, and up-regulating GPX4 expression to inhibit ferroptosis of Mtb infected macrophages through activating Nrf2/HO-1 signaling. Moreover, Rif@Man-mPDA NPs-mediated PTT could effectively activate host cell immune responses by promoting autophagy of Mtb infected macrophages, which thus synergizes targeted drug delivery and ferroptosis inhibition for more effective intracellular Mtb clearance. This Rif@Man-mPDA NPs-mediated PTT strategy could also effectively inhibit the Mtb burdens and alleviate the pathological lesions induced by Mtb infection without significant systemic side effects in mouse CTB model. These results indicate that Rif@Man-mPDA NPs-mediated PTT can be served as a novel anti-TB strategy against CTB by synergizing macrophage targeted photothermal therapy and host immune defenses, thus holding promise for more effective treatment strategy development against CTB.

15.
Lasers Med Sci ; 39(1): 241, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39320555

RESUMO

Laryngeal cancer is the second most common cancer in the upper aerodigestive tract, with its incidence increasing across all ages. The conventional treatments for laryngeal cancer include surgical procedure, radiation, and chemotherapy; however, these treatments can lead to various complications. Photothermal therapy (PTT) using laser light has been employed form cancer effective treatment because of its minimal invasion and short operation time. The current study aims to investigate the feasibility of 532 nm PTT on laryngeal cancer in an invivo tumor model. Ex vivo dosimetry evaluation was conducted to determine the laser irradiation conditions, and HEP-2 tumor bearing mice were used to demonstrate in vivo photothermal effects. In addition, histology and western blot analysis were conducted to verify tumor necrosis and any changes in cancer-associated factors in the tumor tissues. The current in vivo results showed that PTT at 5 W for 40 s and 20 W for 10 s had comparable effects in terms of temperature increase and tumor removal. The 532 nm PTT significantly decreased the remaining tumor and downregulated the expression levels of MMP- 9 and ERK. The current study demonstrated that the 532 nm PTT could be a feasible option for treatment of laryngeal tumor with high power delivery for a short exposure time. Further investigations will confirm the endoscopic application of the 532 nm PTT for the treatment of intralaryngeal tissue prior to clinical translation.


Assuntos
Neoplasias Laríngeas , Terapia Fototérmica , Animais , Neoplasias Laríngeas/terapia , Neoplasias Laríngeas/radioterapia , Neoplasias Laríngeas/patologia , Camundongos , Humanos , Terapia Fototérmica/métodos , Linhagem Celular Tumoral , Modelos Animais de Doenças
16.
Colloids Surf B Biointerfaces ; 245: 114258, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39303384

RESUMO

Exosome-liposome hybrid-based vehicles (ELV) are promising carriers for cancer treatment, but there are rare efficient theranostic probes to label their lipid bilayer membrane for precisely tracing biodistribution and execute potent therapy. As both fluorescence imaging and photothermal therapy in the second near-infrared window (NIR-II) has intrinsically deep penetration and high efficacy to ablate tumors, herein the design and synthesis of lipophilic NIR-II cyanine dyes with strong donor strength is reported to label lipid bilayer membrane of ELV for NIR-II fluorescence image-guided and targeted NIR-II photothermal treatment of subcutaneous glioblastoma. Via lipid film hydration and subsequent extrusion method, the synthesized ELV (NIR-C12-EL) is formulated with NIR-C12 labeling, cyclic arginylglycylaspartic acid decoration, liposomal PEGylation, and biological exosome function. NIR-C12-EL exhibits excellent colloidal stability, good biocompatibility, strong light harvesting capability, high NIR-II photoconversion efficiency (62.28 %), and targeting capability to diagnose and ablate tumors, which together contribute to the extended life-span of the mice treatment with NIR-C12-EL and continuous 1064 nm laser irradiation. This study provides insight into not only designing of lipophilic NIR-II fluorescence probes for labeling of exosome-liposome hybrid-based vehicles but also the engineering of theranostic nanoplatforms for precise treatment of glioblastoma.

17.
Artigo em Inglês | MEDLINE | ID: mdl-39319421

RESUMO

Photothermal therapy (PTT) encounters challenges of rapid thermal loss and potential tissue damage. In response, we propose a Heat-Boost and Lock implant coating strategy inspired by the thermal adaptation of biological membranes, enabling precise local photothermal utilization. This coating incorporates a poly(tannic acid) (pTA) bridging layer on implants, facilitating stable layer-by-layer integration of a black phosphorus (BP) photothermal layer and a top cell membrane Heat-Boost and Lock layer. The cell membrane layer significantly curtails photothermal loss (extending the heat retention by 17.62%) and stores energy within its phospholipid bilayer, boosting photothermal effects near implants (achieving a temperature increasement of 275%). Theoretical analysis indicates that these local heat preservation properties of the cell membrane arise from its low thermal conductivity and phase-change properties. In a Staphylococcus aureus-infected bone implant model, our coating demonstrates precise antibacterial action around implants (reach an antibacterial ratio of 99.52%). The synergetic locking function of cell membrane and pTA delays BP biodegradation, ensuring favorable photothermal stability and long-term osteo-inductive performance (increasing the bone volume fraction by 53.45%). Beyond providing an endogenic biointerface, this strategy extends the application of cell membrane in local thermal management, offering possibilities for effective and safe PTT modalities.

18.
Angew Chem Int Ed Engl ; : e202416828, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39319629

RESUMO

The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) has become an attractive tumor treatment modality, yet the facile design of photoimmunotheranostic agents with efficient near infrared (NIR) light-absorbing and immune- activating capabilities remains a tremendous challenge. Herein, we developed a NIR-activable organic charge transfer complex (CTC), with perylene (PER) as the electron donor and 4,5,9,10-tetrabromoisochromeno [6,5,4-def]isochromene-1,3,6,8-tetraone (Br4NDI) as the electron acceptor. Through further supramolecular assembly, the PER-Br4NDI nanoparticle (PBND NP) for spatiotemporally controlled photoimmunotherapy was constructed. The PBND NP exhibits superb NIR absorption, robust intermolecular charge transfer, and enhanced intersystem crossing. Upon NIR photoirradiation, the PBND NP effectively exerts photothermal and photodynamic effects with a remarkable photothermal conversion efficiency of 63.5% and a high reactive oxygen species generation capability, which not only directly ablates primary tumors, but also dramatically suppresses distant tumor growth via promoted immunogenic cell death. Moreover, programmed cell death protein 1 antibody acts synergistically to block immune evasion and ultimately enhances cancer treatment efficacy. This work therefore sheds light on the design of organic CTCs for synergistic photoimmunotherapy.

19.
Ther Deliv ; : 1-19, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39314189

RESUMO

Superficial cancers typically refer to cancers confined to the surface layers of tissue. Low-targeting therapies or side effects prompt exploration of novel therapeutic approaches. Gold nanoparticles (AuNPs), due to their unique optical properties, serve as effective photosensitizers, enabling tumor ablation through photothermal therapy (PTT). PTT induced by AuNPs can be achieved through light sources externally applied to the skin. Near-infrared radiation is the main light candidate due to its deep tissue penetration capability. This review explores recent advancements in AuNP-based PTT for superficial cancers, specifically breast, head and neck, thyroid, bladder and prostate cancers. Additionally, challenges and future directions in utilizing AuNPs for cancer treatment are discussed, emphasizing the importance of balancing efficacy with safety in clinical applications.


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20.
Adv Healthc Mater ; : e2402505, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39233538

RESUMO

Achieving the clinically staged treatment of osteosarcoma-associated bone defects encounters the multiple challenges of promptly removing postoperative residual tumor cells and bacterial infection, followed by bone reconstruction. Herein, a core/shell hydrogel with multiple-effect combination is designed to first exert antitumor and antibacterial activities and then promote osteogenesis. Specifically, doxorubicin (DOX) is loaded by magnesium-iron-based layered double hydroxide (LDH) to prepare LDOX, which is introduced into a thermo-sensitive hydrogel to serve as an outer shell of the core/shell hydrogel, meanwhile, LDH-contained liquid crystal hydrogel, abbreviated as LCgel-L, is served as an inner core. At the early stage of treatment, the dissociation of the outer shell triggered by moderate hyperthermia led to the thermo-sensitive release of LDOX, which can be targeted for the release of DOX within tumor cells, thereby promptly removing postoperative residual tumor cells based on the synergistic effect of photothermal therapy (PTT) and DOX, and postoperative bacterial infection can also be effectively prevented by PTT simultaneously. More importantly, the dissociation of the outer shell prompted the full exposure of the inner core, which will exert osteogenic activity based on the synergy of liquid crystal hydrogel as well as LDH-induced mild hyperthermia and ion effects, thereby enabling "temporal regulation" treatment of osteosarcoma-associated bone defects. This study provides a valuable insight for the development of osteosarcoma-associated bone repair materials.

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