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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.
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
4.
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
5.
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
6.
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
7.
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
8.
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
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.
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
11.
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
12.
ACS Appl Bio Mater ; 7(9): 5861-5884, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39192748

RESUMO

The evolution of targeted cancer theranostics has revolutionized personalized medicine by integrating diagnostic and therapeutic capabilities. Prostate-specific membrane antigen (PSMA) has emerged as a key theranostic target in the context of prostate cancer, paving the way for the clinical approval of multiple drugs. However, the persistent challenge of off-target toxicity, which plagues both conventional and advanced treatment modalities such as targeted chemotherapy and radiotherapy, thus demands further innovation. Considering this critical issue, this review discusses the recent advances in the binary treatment techniques, i.e., phototherapies, that have the potential to circumvent the key concern of off-target toxicity associated with personalized chemotherapy and radiotherapy. Precisely, an up-to-date overview of the latest developments in the near-infrared (NIR)-based phototheranostic strategies for prostate cancer by targeting PSMA has been presented. Furthermore, we have discussed the associated particulars that require specific attention in enhancing the translational potential of phototheranostic techniques.


Assuntos
Raios Infravermelhos , Neoplasias da Próstata , Nanomedicina Teranóstica , Humanos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Masculino , Glutamato Carboxipeptidase II/metabolismo , Antígenos de Superfície/metabolismo , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Fototerapia , Animais , Teste de Materiais , Antineoplásicos/química , Antineoplásicos/farmacologia , Tamanho da Partícula
13.
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
14.
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
15.
J Photochem Photobiol B ; 259: 112993, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39128426

RESUMO

To increase the therapeutic efficacy of nanoparticle (NP)-assisted photothermal therapy (PTT) and allow for a transition toward the clinical setting, it is pivotal to characterize the thermal effect induced in cancer cells and correlate it with the cell biological response, namely cell viability and cell death pathways. This study quantitatively evaluated the effects of gold nanorod (GNR)-assisted near-infrared (NIR) PTT on two different cancer cell lines, the 4T1 triple-negative breast cancer cells and the Pan02 pancreatic cancer cells. The interaction between nanomaterials and biological matrices was investigated in terms of GNR internalization and effect on cell viability at different GNR concentrations. GNR-mediated PTT was executed on both cell lines, at the same treatment settings to allow a straightforward comparison, and real-time monitored through thermographic imaging. A thermal analysis based on various parameters (i.e., maximum absolute temperature, maximum temperature change, temperature variation profile, area under the time-temperature change curve, effective thermal enhancement (ETE), and time constants) was performed to evaluate the treatment thermal outcome. While GNR treatment and NIR laser irradiation alone did not cause cell toxicity in the selected settings, their combination induced a significant reduction of cell viability in both cell lines. At the optimal experimental condition (i.e., 6 µg/mL of GNRs and 4.5 W/cm2 laser power density), GNR-assisted PTT reduced the cell viability of 4T1 and Pan02 cells by 94% and 87% and it was associated with maximum temperature changes of 25 °C and 29 °C (i.e., ∼1.8-fold increase compared to the laser-only condition), maximum absolute temperatures of 55 °C and 54 °C, and ETE values of 78% and 81%, for 4T1 and Pan02 cells, correspondingly. Also, the increase in the GNR concentration led to a decrease in the time constants, denoting faster heating kinetics upon irradiation. Furthermore, the thermal analysis parameters were correlated with the extent of cell death. Twelve hours after NIR exposure, GNR-assisted PTT was found to mainly trigger secondary apoptosis in both cell lines. The proposed study provides relevant insights into the relationship between temperature history and biological responses in the context of PTT. The findings contribute to the development of a universal methodology for evaluating thermal sensitivity upon NP-assisted PTT on different cell types and lay the groundwork for future translational studies.


Assuntos
Sobrevivência Celular , Ouro , Raios Infravermelhos , Nanotubos , Neoplasias Pancreáticas , Terapia Fototérmica , Ouro/química , Nanotubos/química , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/patologia , Humanos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Feminino , Animais , Camundongos , Neoplasias da Mama/terapia , Neoplasias da Mama/patologia , Temperatura , Fototerapia
16.
Sci Rep ; 14(1): 18368, 2024 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-39112627

RESUMO

The aim of this study was to investigate the overall effects of phototherapy on biopterin (BH4), neopterin (BH2), tryptophan (Trp), and behavioral neuroinflammatory reaction in patients with post-stroke depression. There involved a total of 100 hospitalized patients with post-stroke depression at our hospital from February 2021 to December 2022. The participants enrolled were randomly assigned to either the control group or the experimental group. The control group received routine treatment, including medication and psychological support, while the experimental group received 30 min of phototherapy daily for 8 weeks. All participantsvoluntarily participated in the study and provided informed consent. Baseline characteristics of the patients were statistically analyzed. The severity of depressive symptoms was evaluated using the hamilton depression scale (HAMD) and the beck depression inventory (BDI). Levels of amino acid neurotransmitters, including gamma-aminobutyric acid (GABA), aspartic acid (Asp), and glutamic acid (Glu), were measured using radioimmunoassay. Plasma levels of neuroinflammatory factors, such as TNF-α, IL-6, and IL-1ß were, determined using ELISA. Plasma levels of BH4, BH2, and Trp were detected by HPLC. Levels of SOD, GPx, CAT, and MDA in plasma were measured using corresponding kits and colorimetry. Quality of life was assessed using the SF-36 scale. There were no differences in baseline characteristic between the two groups (P > 0.05). The HAMD and BDI scores in the experimental group were lower than those in the control group (P < 0.05), indicating phototherapy could reduce the severity of post-stroke depression. The levels of GABA, Glu, and Asp in both groups significantly increased after treatment compared to their respective levels before treatment (P < 0.01).The levels of GABA in the experimental group were higher than those in the control group (P < 0.01),while the levels of Glu, and Asp were lower than those in the control group (P < 0.01). The plasma levels of TNF-α, IL-6, and IL-1ß in the experimental group were evidently lower than those in the control group (P < 0.05). Moreover, the levels of BH4 and Trp in experimental group were significantly higher than those in the control group (P < 0.05), while the levelsof BH2 in the experimental group were significantly lower than the control group (P < 0.05). Additionally, the levels of SOD, GPx, and CAT in the experimental group were evidently higher than those in the control group (P < 0.05), whereas the levels of MDA in the experimental group were significantly lower than control group (P < 0.05). The experimental group showed higher scores in physical function, mental health, social function, and overall health compared to the control group (P < 0.05). Phototherapy exerted a profound impact on the metabolism of BH4, BH2, and Trp, as well as on behavioral neuroinflammatory reactions and the quality of life in patients suffering from post-stroke depression. Through its ability to optimize the secretion and synthesis of neurotransmitters, phototherapy effectively regulated neuroinflammatory reactions, improved biochemical parameters, enhancedantioxidant capacity, and alleviated depressive symptoms. As a result, phototherapy was considered a valuable adjuvant therapeutic approach for patients with post-stroke depression.


Assuntos
Biopterinas , Depressão , Neopterina , Fototerapia , Acidente Vascular Cerebral , Triptofano , Humanos , Neopterina/sangue , Triptofano/sangue , Triptofano/metabolismo , Feminino , Masculino , Pessoa de Meia-Idade , Depressão/terapia , Depressão/etiologia , Depressão/sangue , Idoso , Fototerapia/métodos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/psicologia , Biopterinas/análogos & derivados , Doenças Neuroinflamatórias/terapia , Doenças Neuroinflamatórias/etiologia
17.
Int J Nanomedicine ; 19: 7963-7981, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39130689

RESUMO

Introduction: Traditional cancer treatment strategies often have severe toxic side effects and poor therapeutic efficacy. To address the long-standing problems related to overcoming the complexity of tumors, we develop a novel nanozyme based on the in situ oxidation of 2D Ti3C2 structure to perform simultaneous phototherapy and sonodynamic therapy on tumors. Ti3C2 nanozymes exhibit multi-enzyme activity, including intrinsic peroxidase (POD) activities, which can react with H2O2 in the tumor microenvironment. This new material can construct Ti3C2/TiO2 heterostructures in vivo. Methods: Photothermal (PTT), sonodynamic (SDT) effects, and photoacoustic (PA) image-guided synergy therapy can be achieved. Finally, anticancer immune responses occur with this nanozyme. In vivo experiments revealed that the Ti3C2/TiO2 heterostructure inhibited tumor growth. Results: Complementarily, our results showed that the Ti3C2/TiO2 heterostructure enhanced the immunogenic activity of tumors by recruiting cytotoxic T cells, thereby enhancing the tumor ablation effect. Mechanistic studies consistently indicated that Reactive Oxygen Species (ROS) regulates apoptosis of HCC cells by modulating NRF2/OSGIN1 signaling both in vitro and in vivo. As a result, Ti3C2 nanozyme effectively inhibited tumor through its synergistic ability to modulate ROS and enhance immune infiltration of cytotoxic T cells in the tumor microenvironment. Discussion: These findings open up new avenues for enhancing 2D Ti3C2 nanosheets and suggest a new way to develop more effective sonosensitizers for the treatment of cancer.


Assuntos
Titânio , Terapia por Ultrassom , Titânio/química , Titânio/farmacologia , Animais , Camundongos , Humanos , Terapia por Ultrassom/métodos , Nanopartículas/química , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Microambiente Tumoral/efeitos dos fármacos , Fototerapia/métodos , Camundongos Endogâmicos BALB C , Apoptose/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/tratamento farmacológico , Técnicas Fotoacústicas/métodos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Sci Rep ; 14(1): 18210, 2024 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-39107448

RESUMO

This study aimed to assess the magnitude of hematological toxicity and associated factors in newborns with hyperbilirubinemia. A cross-sectional study was conducted from April to December 2023. A total of 247 newborns were included. The data were collected using questionnaires and a data extraction sheet. Four 4 ml of blood was collected. A Sysmex KX-21 analyzer was used for blood analysis, and a Mindray BS-240 analyzer was used for bilirubin measurement. The data were entered into Epi-data and analyzed by SPSS. The logistic regression was used. The P value was set at 0.05. Before phototherapy, the hematological toxicities, such as anemia, leucopenia, and thrombocytopenia, were 45.7%, 22.2%, and 6.1%, respectively, whereas after phototherapy, anemia and thrombocytopenia, significantly increased, but the leucopenia, significantly decreased. The risk of developing anemia increased, 3.5, 2.7, and 2.1-fold among newborns with bilirubin > 18 mg/dl, with Rh blood group incompatibility, and treated with intensive phototherapy, respectively. Both low birth weight and intensive phototherapy increased the incidence of thrombocytopenia by 2 and 3.4-fold, respectively. Hematological toxicity was found to be a severe public health issue in newborns. Thus, strict follow-up and early detection of toxicity by considering aggravation factors are necessary.


Assuntos
Hiperbilirrubinemia Neonatal , Fototerapia , Humanos , Recém-Nascido , Fototerapia/efeitos adversos , Fototerapia/métodos , Feminino , Masculino , Estudos Transversais , Hiperbilirrubinemia Neonatal/terapia , Hiperbilirrubinemia Neonatal/sangue , Bilirrubina/sangue , Trombocitopenia/sangue , Trombocitopenia/terapia , Anemia/sangue , Anemia/terapia , Fatores de Risco
19.
J Drugs Dermatol ; 23(8): 626-631, 2024 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-39093642

RESUMO

Palmoplantar pustulosis is a variant of psoriasis and a chronic skin disorder in which pruritic pustular eruptions appear on the palms and soles. It is thought to arise from a variety of genetic and environmental factors, is limited in prevalence, and has proven quite difficult to treat. The symptoms it inflicts on those affected are quite debilitating and the treatment landscape is constantly evolving, thus emphasizing the need for updates of the literature as time passes. Current treatments include topical agents, oral therapies, and phototherapy, amongst other treatments. In this systemic review, we explore newer literature from 2015 to 2022 on various treatment regimens for palmoplantar pustulosis. J Drugs Dermatol. 2024;23(8):626-631.     doi:10.36849/JDD.doi:10.36849/7612R1.


Assuntos
Fármacos Dermatológicos , Psoríase , Humanos , Psoríase/terapia , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Fármacos Dermatológicos/uso terapêutico , Fármacos Dermatológicos/administração & dosagem , Fototerapia/métodos , Administração Oral , Administração Cutânea , Resultado do Tratamento
20.
Photodermatol Photoimmunol Photomed ; 40(5): e12997, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39166268

RESUMO

BACKGROUND: Cutaneous graft-versus-host disease (GVHD) is a common complication of allogeneic hematopoietic stem cell transplantation. Phototherapy has been used to treat cutaneous GVHD, but data on its safety and efficacy are sparse. AIM: Review the current medical literature regarding the efficacy, dosing, and safety of various types of phototherapies for the treatment of cutaneous GVHD. METHODS: A systematic review of PubMed, Embase, Cochrane, and ClinicalTrials databases was performed. Publications were screened according to the PRISMA guidelines. Exclusion criteria comprised case reports and case series reporting less than five patients, review articles, and articles not published in English. RESULTS: A total of 28/1304 (2.5%) studies were included. Fifteen studies (n = 267 patients) focused on psoralen and ultraviolet (UV) A (PUVA), in which 65.5% of patients received concomitantly other systemic treatments. The response rate was 89.9%, with a mean of 33.2 treatments. Adverse events were recorded in 54% but were mainly mild. Eight studies, encompassing 95 patients, focused on narrow-band (NB) UVB. A response was observed in 94%, with a mean number of 26 treatments and 8.6% adverse effects. UVA1 was reported in six studies (n = 132 patients). A response was recorded in 89.3% with a mean of 26.2 treatments. Adverse events were noted in 70.1%, with a discontinuation rate of 10.9%. It should be noted that adverse events were recorded during the follow-up period of the studies, which varied significantly, ranging from no follow-up to 31 months. CONCLUSIONS: Current data regarding the use of phototherapy for the treatment of cutaneous GVHD are based on retrospective studies and case series. The present report advocates the use of one of the three modalities of phototherapy as an effective and safe adjunctive treatment for cutaneous GVHD, especially NB UVB phototherapy.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Doença Enxerto-Hospedeiro/terapia , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Terapia PUVA , Dermatopatias/terapia , Fototerapia
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