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1.
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
2.
Biomaterials ; 312: 122709, 2025 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39094521

RESUMO

Sonodynamic therapy (SDT) relies heavily on the presence of oxygen to induce cell death. Its effectiveness is thus diminished in the hypoxic regions of tumor tissue. To address this issue, the exploration of ultrasound-based synergistic treatment modalities has become a significant research focus. Here, we report an ultrasonic cavitation effect enhanced sonodynamic and 1208 nm photo-induced cancer treatment strategy based on thermoelectric/piezoelectric oxygen-defect bismuth oxychloride nanosheets (BNs) to realize the high-performance eradication of tumors. Upon ultrasonic irradiation, the local high temperature and high pressure generated by the ultrasonic cavitation effect combined with the thermoelectric and piezoelectric effects of BNs create a built-in electric field. This facilitates the separation of carriers, increasing their mobility and extending their lifetimes, thereby greatly improving the effectiveness of SDT and NIR-Ⅱ phototherapy on hypoxia. The Tween-20 modified BNs (TBNs) demonstrate ∼88.6 % elimination rate against deep-seated tumor cells under hypoxic conditions. In vivo experiments confirm the excellent antitumor efficacy of TBNs, achieving complete tumor elimination within 10 days with no recurrences. Furthermore, due to the high X-ray attenuation of Bi and excellent NIR-Ⅱ absorption, TBNs enable precise cancer diagnosis through photoacoustic (PA) imaging and computed tomography (CT).


Assuntos
Bismuto , Neoplasias da Mama , Oxigênio , Terapia por Ultrassom , Bismuto/química , Feminino , Animais , Neoplasias da Mama/terapia , Terapia por Ultrassom/métodos , Oxigênio/química , Camundongos , Camundongos Endogâmicos BALB C , Humanos , Linhagem Celular Tumoral , Raios Infravermelhos , Nanoestruturas/química , Fototerapia/métodos
3.
J Nanobiotechnology ; 22(1): 558, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39267061

RESUMO

Breast cancer therapy has significantly advanced by targeting the programmed cell death-ligand 1/programmed cell death-1 (PD-L1/PD-1) pathway. BMS-202 (a smallmolecule PD-L1 inhibitor) induces PD-L1 dimerization to block PD-1/PD-L1 interactions, allowing the T-cell-mediated immune response to kill tumor cells. However, immunotherapy alone has limited effects. Clinically approved photodynamic therapy (PDT) activates immunity and selectively targets malignant cells. However, PDT aggravates hypoxia, which may compromise its therapeutic efficacy and promote tumor metastasis. We designed a tumor-specific delivery nanoplatform of liposomes that encapsulate the hypoxia-sensitive antitumor drug tirapazamine (TPZ) and the small-molecule immunosuppressant BMS. New indocyanine green (IR820)-loaded polyethylenimine-folic acid (PEI-FA) was complexed with TPZ and BMS-loaded liposomes via electrostatic interactions to form lipid nanocomposites. This nanoplatform can be triggered by near-infrared irradiation to induce PDT, resulting in a hypoxic tumor environment and activation of the prodrug TPZ to achieve efficient chemotherapy. The in vitro and in vivo studies demonstrated excellent combined PDT, chemotherapy, and immunotherapy effects on the regression of distant tumors and lung metastases, providing a reference method for the preparation of targeted agents for treating breast cancer.


Assuntos
Neoplasias da Mama , Imunoterapia , Lipossomos , Lipossomos/química , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/terapia , Imunoterapia/métodos , Animais , Camundongos , Humanos , Linhagem Celular Tumoral , Fotoquimioterapia/métodos , Verde de Indocianina/química , Verde de Indocianina/uso terapêutico , Verde de Indocianina/análogos & derivados , Camundongos Endogâmicos BALB C , Tirapazamina/química , Tirapazamina/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Fototerapia/métodos
4.
Arch Dermatol Res ; 316(9): 632, 2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39305310

RESUMO

Ultraviolet B narrow band (UVB-NB) phototherapy is the gold standard treatment for vitiligo, primarily due to its immunomodulatory effects. Additionally, it may influence circadian melatonin balance, that may indirectly induce sleep regulation, which in turn could potentially contribute to vitiligo improvement. The association between melatonin, vitiligo and phototherapy has been little investigated. The aim of this study was to evaluate the current evidence regarding the effects of circadian melatonin regulation and sleep, particularly during vitiligo treatment with phototherapy. We undertook a narrative review to synthetize the evidence on this association through the MEDLINE/PubMed database, using combined search terms: melatonin, vitiligo, phototherapy, and circadian rhythm (sleep). A total of 56 articles were included. There are few studies on this relationship, and conflicting findings. Some studies have suggested that UV exposure and phototherapy might benefit vitiligo by stimulating melanocytes, which have melatonin receptors, and this could potentially synchronize the circadian regulation of melatonin. This improved melatonin balance could result in better sleep quality further enhancing the antiinflammatory properties of melatonin and contributing to vitiligo improvement. Less is known about the possible effects of the use of topical melatonin, with or without phototherapy, to treat vitiligo lesions. In conclusion, there is some evidence that circadian melatonin regulation plays an important role in the course of vitiligo, both through sleep regulation and its anti-inflammatory properties. The evidence suggests that the systemic and physiological properties of melatonin, especially its circadian behavior regulated by phototherapy, may be more effective in respect of vitiligo improvement than the use of topical melatonin. However, the effects of the oral intake of melatonin are less clear. Phototherapy, as a potential modulator of circadian melatonin rhythm, that influences sleep and clinical improvement of vitiligo, needs further examination, as does the use of melatonin as an adjuvant treatment to UVB phototherapy in vitiligo.


Assuntos
Ritmo Circadiano , Melatonina , Sono , Terapia Ultravioleta , Vitiligo , Vitiligo/terapia , Humanos , Melatonina/administração & dosagem , Ritmo Circadiano/fisiologia , Terapia Ultravioleta/métodos , Sono/fisiologia , Fototerapia/métodos , Resultado do Tratamento
5.
Nat Commun ; 15(1): 8187, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39294133

RESUMO

Cancer is a significant cause of death around the world, and for many varieties, treatment is not successful. Therefore, there is a need for the development of innovative, efficacious, and precisely targeted treatments. Here, we develop a series of Au(I) complexes (1-4) through rational manipulation of ligand structures, thereby achieving tumor cell specific targeting and orchestrated tumor eradication via chemo-phototherapy and induced immunogenic cell death. A comprehensive exploration based on in vitro and in vivo female mice experimentation shows that complex 4 exhibits proficiency in specific tumor imaging, endoplasmic reticulum targeting, and has robust therapeutic capabilities. Mechanistic elucidation indicates that the anticancer effect derives from the synergistic actions of thioredoxin reductase inhibition, highly efficient reactive oxygen species production and immunogenic cell death. This work presents a report on a robust Au(I) complex integrating three therapeutic modalities within a singular system. The strategy presented in this work provides a valuable reference for the development of high-performance therapeutic agents.


Assuntos
Ouro , Morte Celular Imunogênica , Espécies Reativas de Oxigênio , Animais , Ouro/química , Morte Celular Imunogênica/efeitos dos fármacos , Feminino , Camundongos , Humanos , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Tiorredoxina Dissulfeto Redutase/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias/terapia , Neoplasias/imunologia , Fototerapia/métodos , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/uso terapêutico
6.
Front Immunol ; 15: 1420463, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39308869

RESUMO

With the outbreak of the coronavirus disease 2019 (COVID-19), reductions in T-cell function and exhaustion have been observed in patients post-infection of COVID-19. T cells are key mediators of anti-infection and antitumor, and their exhaustion increases the risk of compromised immune function and elevated susceptibility to cancer. Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer with high incidence and mortality. Although the survival rate after standard treatment such as surgical treatment and chemotherapy has improved, the therapeutic effect is still limited due to drug resistance, side effects, and recurrence. Recent advances in molecular biology and immunology enable the development of highly targeted therapy and immunotherapy for cancer, which has driven cancer therapies into individualized treatments and gradually entered clinicians' views for treating NSCLC. Currently, with the development of photosensitizer materials, phototherapy has been gradually applied to the treatment of NSCLC. This review provides an overview of recent advancements and limitations in different treatment strategies for NSCLC under the background of COVID-19. We discuss the latest advances in phototherapy as a promising treatment method for NSCLC. After critically examining the successes, challenges, and prospects associated with these treatment modalities, their profound prospects were portrayed.


Assuntos
COVID-19 , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , SARS-CoV-2 , Humanos , Carcinoma Pulmonar de Células não Pequenas/terapia , COVID-19/terapia , COVID-19/imunologia , Neoplasias Pulmonares/terapia , SARS-CoV-2/fisiologia , Fototerapia/métodos , Terapia Combinada , Imunoterapia/métodos
8.
Physiother Res Int ; 29(4): e2129, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39223951

RESUMO

OBJECTIVE: Vulvovaginal Candidiasis (VVC) is a prevalent genital infection in women of reproductive age and requires effective non-drug therapies. Therefore, this study aimed to investigate the effect of blue light emitting diode (LED) therapy as an alternative treatment for recurrent VVC due to its proven antimicrobial properties. The safety and non-invasiveness of LED therapy make it a promising option for sensitive tissue applications. MATERIALS AND METHODS: This randomized controlled trial recruited 60 women with culture-confirmed VVC. Participants were randomly allocated to two groups. Group A (control group) received standard antifungal treatment with Gynoconazol 0.8% vaginal cream for three consecutive nights (n = 30). Group B (study group) received the same antifungal treatment plus two 60-min sessions of blue LED therapy directed at the vagina and vulva, with the sessions separated by two days (n = 30). Candida count (via CHROMagar™ Candida) and vaginal pH (via AD110-AD111 m) were assessed at baseline and one week after initiating treatment. RESULTS: Post-treatment, group (B) demonstrated a significantly greater reduction in Candida count compared to group (A) (mean difference (MD) 8.267; 95% Confidence Interval (CI) 6.723-9.811; p = 0.0001). However, there was no statistically significant difference in vaginal pH between the groups (MD -0.03; 95% CI -0.244-0.178; p = 0.749). CONCLUSION: Blue LED therapy effectively reduces Candida count in women with recurrent VVC without adversely affecting the vaginal pH, highlighting its safety and efficacy as a treatment modality.


Assuntos
Candidíase Vulvovaginal , Humanos , Feminino , Candidíase Vulvovaginal/terapia , Candidíase Vulvovaginal/tratamento farmacológico , Adulto , Fototerapia/métodos , Antifúngicos/uso terapêutico , Recidiva , Adulto Jovem , Método Simples-Cego , Resultado do Tratamento , Luz Azul
9.
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
10.
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
11.
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
12.
Int J Nanomedicine ; 19: 9071-9090, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39253059

RESUMO

Purpose: Our study seeks to develop dual-modal organic-nanoagents for cancer therapy and real-time fluorescence imaging, followed by their pre-clinical evaluation on a murine model. Integrating NIR molecular imaging with nanotechnology, our aim is to improve outcomes for early-stage cutaneous melanoma by offering more effective and less invasive methods. This approach has the potential to enhance both photothermal therapy (PTT) and Sentinel Lymph Node Biopsy (SLNB) procedures for melanoma patients. Methods: NIR-797-isothiocyanate was encapsulated in poly(D,L-lactide-co-glycolide) acid (PLGA) nanoparticles (NPs) using a two-step protocol, followed by thorough characterization, including assessing loading efficiency, fluorescence stability, and photothermal conversion. Biocompatibility and cellular uptake were tested in vitro on melanoma cells, while PTT assay, with real-time thermal monitoring, was performed in vivo on tumor-bearing mice under irradiation with an 808 nm laser. Finally, ex vivo fluorescence microscopy, histopathological assay, and TEM imaging were performed. Results: Our PLGA NPs, with a diameter of 270 nm, negative charge, and 60% NIR-797 loading efficiency, demonstrated excellent stability and fluorescence properties, as well as efficient light-to-heat conversion. In vitro studies confirmed their biocompatibility and cellular internalization. In vivo experiments demonstrated their efficacy as photothermal agents, inducing mild hyperthermia with temperatures reaching up to 43.8 °C. Ex vivo microscopy of tumor tissue confirmed persistent NIR fluorescence and uniform distribution of the NPs. Histopathological and TEM assays revealed early apoptosis, immune cell response, ultrastructural damage, and intracellular material debris resulting from combined NP treatment and irradiation. Additionally, TEM analyses of irradiated zone margins showed attenuated cellular damage, highlighting the precision and effectiveness of our targeted treatment approach. Conclusion: Specifically tailored for dual-modal NIR functionality, our NPs offer a novel approach in cancer PTT and real-time fluorescence monitoring, signaling a promising avenue toward clinical translation.


Assuntos
Hipertermia Induzida , Nanopartículas , Imagem Óptica , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Animais , Nanopartículas/química , Camundongos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Linhagem Celular Tumoral , Hipertermia Induzida/métodos , Humanos , Terapia Fototérmica/métodos , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/patologia , Melanoma/terapia , Melanoma/diagnóstico por imagem , Fototerapia/métodos
13.
Adv Exp Med Biol ; 1456: 93-126, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39261426

RESUMO

For many of the complementary and alternative (CAM) medicine methods, it is biologically plausible to expect that they could provide additional benefits in the treatment of major depressive disorder (e.g., enhanced initial response, augmentation, and tolerability) when combined with conventional treatments. Although most likely not comprehensively, herein we critically review current explicit clinical data pertaining to the most extensively evaluated CAMs in this setting: physical activity/exercise, mind and body methods, acupuncture, light therapy, diet, probiotics, various nutrients, and herbal preparations. While the absolute amount of data is enormous, the number of reliable primary studies (randomized controlled trials) and, particularly, meaningful meta-analyses of such studies are very limited. Consequently, the certainty of evidence about benefit or no benefit is very low for each of the addressed CAMs.


Assuntos
Terapias Complementares , Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/terapia , Terapias Complementares/métodos , Terapia Combinada , Probióticos/uso terapêutico , Terapia por Acupuntura/métodos , Fototerapia/métodos , Resultado do Tratamento , Terapias Mente-Corpo/métodos , Exercício Físico
14.
Theranostics ; 14(12): 4667-4682, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39239517

RESUMO

Background: Effective innate immunity activation could dramatically improve the anti-tumor efficacy and increase the beneficiary population of immunotherapy. However, the anti-tumor effect of unimodal immunotherapy is still not satisfactory. Methods: Herein, a novel relay-type innate immunity activation strategy based on photo-immunotherapy mediated by a water-soluble aggregation-induced emission luminogen, PEG420-TQ, with the assistant of toll-like receptor 7 (TLR-7) agonist, imiquimod (R837), was developed and constructed. Results: The strategy could promote tumor cells to undergo immunogenic cell death (ICD) induced by the well-designed PEG420-TQ@R837 (PTQ@R) nanoplatform under light irradiation, which in turn enhanced the infiltration of immune cells and the activation of innate immune cells to achieve the first innate immunity activation. The second innate immunity activation was subsequently achieved by drug delivery of R837 via apoptotic bodies (ApoBDs), further enhancing the anti-tumor activity of infiltrated immune cells. Conclusion: The strategy ultimately demonstrated robust innate immunity activation and achieved excellent performance against tumor growth and metastasis. The construction of the relay-type innate immunity activation strategy could provide a new idea for the application of immunotherapy in clinical trials.


Assuntos
Imiquimode , Imunidade Inata , Imunoterapia , Imunidade Inata/efeitos dos fármacos , Animais , Imunoterapia/métodos , Camundongos , Imiquimode/uso terapêutico , Imiquimode/farmacologia , Linhagem Celular Tumoral , Humanos , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Água/química , Receptor 7 Toll-Like/agonistas , Feminino , Fototerapia/métodos , Nanopartículas/química , Camundongos Endogâmicos BALB C , Morte Celular Imunogênica/efeitos dos fármacos , Raios Infravermelhos
15.
Biosens Bioelectron ; 266: 116722, 2024 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-39232431

RESUMO

Hepatocellular carcinoma (HCC) is a serious health issue due to its low early diagnosis rate, resistance to chemotherapy, and poor five-year survival rate. Therefore, it is crucial to explore novel diagnostic and therapeutic approaches tailored to the characteristics of HCC. Aggregation-induced emission (AIE) is a phenomenon where the luminescence of certain molecules, typically non-luminescent or weakly luminescent in solution, is significantly enhanced upon aggregation. AIE has been extensively applied in bioimaging, biosensors, and therapy. Fluorophore materials based on AIE (AIEgens) have a wide range of application scenarios and potential for clinical translation. This review focuses on recent advances in AIE-based strategies for diagnosing and treating HCC. First, the specific functional mechanism of AIE is described. Next, we summarize recent progress in the application of AIE for multimodal imaging, biosensor detection, and phototherapy. Finally, prospects and challenges for the AIE-based application in the diagnosis and therapy of HCC are discussed.


Assuntos
Técnicas Biossensoriais , Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/diagnóstico por imagem , Humanos , Técnicas Biossensoriais/métodos , Corantes Fluorescentes/química , Animais , Fototerapia , Imagem Óptica/métodos , Imagem Multimodal/métodos
16.
J Nanobiotechnology ; 22(1): 542, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39238020

RESUMO

Phototherapy is a promising antitumor modality, which consists of photothermal therapy (PTT) and photodynamic therapy (PDT). However, the efficacy of phototherapy is dramatically hampered by local hypoxia in tumors, overexpression of indoleamine 2,3-dioxygenase (IDO) and programmed cell death ligand-1 (PD-L1) on tumor cells. To address these issues, self-assembled multifunctional polymeric micelles (RIMNA) were developed to co-deliver photosensitizer indocyanine green (ICG), oxygenator MnO2, IDO inhibitor NLG919, and toll-like receptor 4 agonist monophosphoryl lipid A (MPLA). It is worth noting that RIMNA polymeric micelles had good stability, uniform morphology, superior biocompatibility, and intensified PTT/PDT effect. What's more, RIMNA-mediated IDO inhibition combined with programmed death receptor-1 (PD-1)/PD-L1 blockade considerably improved immunosuppression and promoted immune activation. RIMNA-based photoimmunotherapy synergized with PD-1 antibody could remarkably inhibit primary tumor proliferation, as well as stimulate the immunity to greatly suppress lung metastasis and distant tumor growth. This study offers an efficient method to reinforce the efficacy of phototherapy and alleviate immunosuppression, thereby bringing clinical benefits to cancer treatment.


Assuntos
Neoplasias do Colo , Imunoterapia , Micelas , Fototerapia , Polímeros , Receptor de Morte Celular Programada 1 , Animais , Neoplasias do Colo/terapia , Neoplasias do Colo/imunologia , Neoplasias do Colo/tratamento farmacológico , Camundongos , Imunoterapia/métodos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Polímeros/química , Linhagem Celular Tumoral , Fototerapia/métodos , Verde de Indocianina/química , Verde de Indocianina/uso terapêutico , Verde de Indocianina/farmacologia , Camundongos Endogâmicos BALB C , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fotoquimioterapia/métodos , Feminino , Humanos , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Lipídeo A/análogos & derivados
17.
Colloids Surf B Biointerfaces ; 244: 114130, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39121570

RESUMO

The complexity and compensatory evolution of tumors weaken the effectiveness of single antitumor therapies. Therefore, multimodal combination therapies hold great promise in defeating tumors. Herein, we constructed a multi-level regulatory co-delivery system based on chemotherapy, phototherapy, and immunotherapy. Briefly, curcumin (Cur) was prepared as nanoparticles and coated with polydopamine (PDA) to form PCur-NPs, which along with an immune checkpoint inhibitor (indoximod, IND) were then loaded into a thermosensitive Pluronic F127 (F127) hydrogel to form a multifunctional nanocomposite hydrogel (PCur/IND@Gel). The in situ-formed hydrogel exhibited excellent photothermal conversion efficiency and sustained drug release behavior both in vitro and in vivo. In addition, PCur-NPs showed enhanced cellular uptake and cytotoxicity under NIR laser irradiation and induced potent immunogenic cell death (ICD). After intratumoral injection of PCur/IND@Gel, significant apoptosis in 4T1 tumors was induced, dendritic cells in lymph nodes were highly activated, potent CD8+ and CD4+ antitumor immune responses were elicited and regulative T cells in tumors were significantly reduced, which notably inhibited the tumor growth and prolonged the survive time of 4T1 tumor-bearing mice. Therefore, this injectable nanocomposite hydrogel is a promising drug co-delivery platform for chemo-photothermal-immunotherapy of breast tumors.


Assuntos
Neoplasias da Mama , Curcumina , Hidrogéis , Imunoterapia , Indóis , Nanopartículas , Polímeros , Indóis/química , Indóis/farmacologia , Curcumina/química , Curcumina/farmacologia , Polímeros/química , Polímeros/farmacologia , Animais , Nanopartículas/química , Camundongos , Hidrogéis/química , Hidrogéis/farmacologia , Feminino , Imunoterapia/métodos , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/terapia , Camundongos Endogâmicos BALB C , Antineoplásicos/farmacologia , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Fototerapia , Terapia Combinada , Terapia Fototérmica , Tamanho da Partícula , Poloxâmero/química , Ensaios de Seleção de Medicamentos Antitumorais , Sobrevivência Celular/efeitos dos fármacos , Propriedades de Superfície , Linhagem Celular Tumoral , Humanos
18.
ACS Appl Mater Interfaces ; 16(36): 47270-47283, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39189605

RESUMO

In situ vaccines that can stimulate tumor immune response have emerged as a breakthrough in antitumor therapy. However, the immunosuppressed tumor microenvironment and insufficient infiltration of immune cells lead to ineffective antitumor immunity. Hence, a biomimetic carrier-free nanosystem (BCC) to induce synergistic phototherapy/chemotherapy-driven in situ vaccines was designed. A carrier-free nanosystem was developed using phototherapeutic reagents CyI and celastrol as raw materials. In vitro and in vivo studies have shown that under NIR light irradiation, BCC-mediated photo/chemotherapy not only accelerates the release of drugs to deeper parts of tumors, achieving timing and light-controlled drug delivery to result in cell apoptosis, but also effectively stimulates the antitumor response to induce in situ vaccine, which could invoke long-lasting antitumor immunity to inhibit tumor metastasis and eliminate distant tumor. This therapeutic strategy holds promise for priming robust innate and adaptive immune responses, arresting cancer progression, and inducing tumor dormancy.


Assuntos
Vacinas Anticâncer , Imunoterapia , Animais , Camundongos , Vacinas Anticâncer/química , Vacinas Anticâncer/imunologia , Humanos , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/farmacologia , Linhagem Celular Tumoral , Neoplasias/terapia , Neoplasias/imunologia , Microambiente Tumoral/efeitos dos fármacos , Nanopartículas/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Fototerapia , Apoptose/efeitos dos fármacos , Raios Infravermelhos
19.
Chem Commun (Camb) ; 60(73): 9942-9945, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39171688

RESUMO

We designed two series of NIR-II PTAs with D-A or D-A-D structures, in which the introduction of thiophene promotes a bathochromic shift of emission into the NIR-II region, helps to improve the cellular uptake of the PTAs and facilitates NIR-II imaging-guided PDT/PTT cancer phototherapy.


Assuntos
Raios Infravermelhos , Tiofenos , Tiofenos/química , Humanos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Fotoquimioterapia , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Fototerapia , Imagem Óptica , Estrutura Molecular , Animais , Nanomedicina Teranóstica
20.
Langmuir ; 40(36): 19125-19133, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39190551

RESUMO

Chemodynamic therapy is an appealing modality in cancer treatment. However, its therapeutic effectiveness is impeded by insufficient catalytic efficiency and overexpression of glutathione (GSH) at the tumor site. In this study, a poly(o-phenylenediamine) (PoPD)@copper sulfide (CuS) nanoplatform was developed as dual-level reactive oxygen species (ROS) amplifier for enhanced photothermal-chemodynamic therapy. The PoPD@CuS nanoplatform exhibited photothermal performance, chemodynamic performance, and GSH-depleting capability. Alongside its improved photothermal conversion efficiency with tumor pH-responsiveness, the photothermal behavior of PoPD@CuS could elevate chemodynamic activity by regulating the temperature spatiotemporally, leading to increased ROS production. Moreover, GSH depletion of PoPD@CuS could suppress ROS scavenging, further enhancing oxidative stress in the tumor region. Consequently, functioning as a dual-level ROS amplifier, PoPD@CuS showcased remarkable effectiveness in photothermal-chemodynamic combination therapy.


Assuntos
Cobre , Espécies Reativas de Oxigênio , Espécies Reativas de Oxigênio/metabolismo , Cobre/química , Cobre/farmacologia , Humanos , Animais , Fenilenodiaminas/química , Fenilenodiaminas/farmacologia , Glutationa/metabolismo , Glutationa/química , Camundongos , Terapia Fototérmica , Fototerapia/métodos , Linhagem Celular Tumoral , Antineoplásicos/química , Antineoplásicos/farmacologia
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