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Photothermal/Photodynamic Therapy with Immune‐Adjuvant Liposomal Complexes for Effective Gastric Cancer Therapy
摘要： A diagnosis and therapeutic strategy for gastric cancer is developed herein by combining thermosensitive liposomal (TSL)-based photothermal/photodynamics therapy (PTT/PDT) with chemotherapy and adjuvant immunotherapy. IR820, a photothermal agent, paclitaxel (PTX), an antitumor drug, and imiquimod (R837), a Toll-like-receptor-7 agonist, are coencapsulated into a TSL drug delivery system. These formed PTX-R837-IR820@TSL complexes exhibit excellent optical properties, good dispersibility, and stability. Under NIR light irradiation, the measurement of singlet oxygen production and thermal efficiency indicate promising potential of PTX-R837-IR820@TSL complexes for PTT and PDT. Confocal microscopy and small animal NIR imaging demonstrate tumor targeting ability of the liposomal complexes to gastric cancer cells. In vitro cell viability assays and in vivo animal experiments show prominent antitumor efficiency of PTX-R837-IR820@TSL complexes upon NIR light irradiation. This excellent therapeutic efficacy is attributed to the simultaneous chemotherapy and PTT/PDT. Furthermore, the liposomal complexes under NIR irradiation would ablate tumors to generate a pool of tumor-associated antigens, which is able to promote strong antitumor immune responses in the presence of those R837-containing liposomal complexes acted as adjuvant. These results indicate that the multifunctional liposomal complexes could realize a remarkable synergistic therapeutic outcome in gastric carcinoma.
关键词： gastric carcinoma,photothermal therapy,adjuvant immunotherapy,photodynamics therapy
更新于2025-11-14 15:26:12
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Nanoscale reduced graphene oxide-mediated photothermal therapy together with IDO inhibition and PD-L1 blockade synergistically promote antitumor immunity
摘要： Despite the potential efficacy of immune checkpoint blockade for effective treatment of cancer, this therapeutic modality is not generally curative and only a fraction of patients respond. Combination approaches provide strategies to target multiple antitumor immune pathways to induce synergistic antitumor immunity. Here, a multi-combination immunotherapy including photothermal therapy (PTT), indoleamine-2,3-dioxygenase (IDO) inhibition and programmed cell death-ligand 1 (PD-L1) blockade is introduced for inducing synergistic antitumor immunity. We designed a multifunctional IDO inhibitor (IDOi)-loaded reduced graphene oxide (rGO)-based nanosheets (IDOi/rGO nanosheets) with the properties to directly kill tumor cells under laser irradiation and in situ trigger antitumor immune response. In vivo experiments further revealed that the triggered immune response can be synergistically promoted by IDO inhibition and PD-L1 blockade; the responses included the enhancement of tumor-infiltrating lymphocytes (TILs) including CD45+ leukocytes, CD4+ T cells, CD8+ T cells and NK cells, the inhibition of the immune suppression activity of regulator T cells (Tregs) and the production of INF-γ. We also demonstrate that the three combinations of PTT, IDO inhibition and PD-L1 blockade could effectively inhibit the growth of both irradiated tumors and tumors in distant sites without PTT treatment. This work can be thought as an important proof-of-concept to target multiple antitumor immune pathways to induce synergistic antitumor immunity.
关键词： photothermal therapy,reduced graphene oxide,IDO inhibition,combinatorial immunotherapy,PD-L1
更新于2025-09-23 15:23:52
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The capabilities and hope of the combination the new forms of personalized colon cancer treatment – immunotherapy and immune photodynamic therapy
摘要： Introduction: PDT can interfere with cytokine-mediated responses that play an important role in the processes of cancer progression, tumor angiogenesis and metastasis. Therefore, based on the identification of these cancer biomarkers, the therapy of combining various forms of treatment, including immunotherapy and PDT, may be a justified strategy for colorectal cancer treatment that focuses on individualized comprehensive therapy. Method: We reviewed the major approaches on the use of immunotherapy in colorectal cancer, with the special regard to photodynamic therapy, its immunological effect and new oncological treatment directions, connected with adjuvant immunotherapy including use of nanoparticles. Databases such as PubMed, ScienceDirect and Springer were utilized to search the literature for relevant articles. Purpose: To review studies of the immunotherapy in colon cancer and immune response to PDT. Conclusion: Based on the identification of immunological cancer biomarkers, the therapy of combining various forms of treatment, including immunotherapy and PDT, may be a justified strategy for colorectal cancer treatment that focuses on individualized comprehensive therapy.
关键词： cytokines,photodynamic therapy,colorectal cancer,immunotherapy
更新于2025-09-23 15:22:29
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Multifunctional Nanoparticle Loaded Injectable Thermoresponsive Hydrogel as NIR Controlled Release Platform for Local Photothermal Immunotherapy to Prevent Breast Cancer Postoperative Recurrence and Metastases
摘要： For breast cancer patients who have undergone breast-conserving surgery, effective treatments to prevent local recurrences and metastases is very essential. Here, a local injectable therapeutic platform based on a thermo-sensitive PLEL hydrogel with near-infrared (NIR)-stimulated drug release is developed to achieve synergistic photothermal immunotherapy for prevention of breast cancer postoperative relapse. Self-assembled multifunctional nanoparticles (RIC NPs) are composed of three therapeutic components including indocyanine green, a photothermal agent; resiquimod (R848), a TLR-7/8 agonist; and CPG ODNs, a TLR-9 agonist. RIC NPs are physically incorporated into the thermosensitive PLEL hydrogel. The RIC NPs encapsulated PLEL hydrogel (RIC NPs@PLEL) is then locally injected into the tumor resection cavity for local photothermal therapy to ablate residue tumor tissues and produce tumor-associated antigens. At the same time, NIR also triggers the release of immune components CPG ODNs and R848 from thermoresponsive hydrogels PLEL. The released immune components, together with tumor-associated antigens, work as an in situ cancer vaccine for postsurgical immunotherapy by inducing effective and sustained antitumor immune effect. Overall, this work suggests that photothermal immunotherapy based on local hydrogel delivery system has great potential as a promising tool for the postsurgical management of breast cancer to prevent recurrences and metastases.
关键词： cancer recurrence,thermal-responsive hydrogels,immunotherapy,controlled drug release,photothermal
更新于2025-09-23 15:21:01
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Biologically Responsive Plasmonic Assemblies for Second Near-Infrared Window Photoacoustic Imaging-Guided Concurrent Chem-Immunotherapy
摘要： We developed dual biologically responsive nanogapped gold nanoparticle vesicles loaded with immune inhibitor and carried with anticancer polymeric prodrug for synergistic concurrent chemo-immunotherapy against primary and metastatic tumors, along with guided cargo release by photoacoustic (PA) imaging in the second near-infrared (NIR-II) window. The responsive vesicle was prepared by self-assembly of nanogapped gold nanoparticles (AuNNPs) grafted with poly(ethylene glycol) (PEG) and dual pH/GSH-responsive polyprodrug poly(SN38-co-4-vinyl pyridine) (termed as AuNNP@PEG/PSN38VP), showing intense PA signal in the NIR-II window. The effect of the rigidity of hydrophobic polymer PSN38VP on the assembly structures and the formation mechanism of AuNNP@SN38 Ve were elucidated by computational simulations. The immune inhibitor BLZ-945 was encapsulated into the vesicles, resulting in pH-responsive release of BLZ-945 for targeted immunotherapy, followed by the dissociation of the vesicles into single AuNNP@PEG/PSN38VP. The hydrophilic AuNNP@PEG/PSN38VP nanoparticles could penetrate deep into the tumor tissues, and release the anticancer drug SN38 under the reductive environment. PA signal in the NIR-II window in the deep tumor region was obtained. The BLZ-945 loaded vesicle enabled enhanced PA imaging-guided concurrent chemo-immunotherapy efficacy, inhibiting the growth of both primary tumors and metastatic tumors.
关键词： the second NIR window,amphiphilic nanogapped gold nanoparticles,polymeric prodrug,chemo-immunotherapy,photoacoustic imaging
更新于2025-09-23 15:19:57
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Aromatic secondary amine-functionalized fluorescent NO probes: improved detection sensitivity for NO and potential applications in cancer immunotherapy studies
摘要： Tumor-associated macrophages (TAMs), constituting up to 50% of the solid tumor mass and commonly having a pro-tumoral M2 phenotype, are closely associated with decreased survival in patients. Based on the highly dynamic properties of macrophages, in recent years the repolarization of TAMs from pro-tumoral M2 phenotype to anti-tumoral M1 phenotype by various strategies has emerged as a promising cancer immunotherapy approach for improving cancer therapy. Herein, we present an aromatic secondary amine-functionalized Bodipy dye 1 and its mitochondria-targetable derivative Mito1 as fluorescent NO probes for discriminating M1 macrophages from M2 macrophages in terms of their difference in inducible NO synthase (iNOS) levels. The two probes possess the unique ability to simultaneously respond to two secondary oxides of NO, i.e., N2O3 and ONOO-, thus being more sensitive and reliable for reflecting intracellular NO than most of the existing fluorescent NO probes that usually respond to N2O3 only. With 1 as a representative, the discrimination between M1 and M2 macrophages, evaluation of the repolarization of TAMs from pro-tumoral M2 phenotype to anti-tumoral M1 phenotype, and visualization of NO communication during the immune-mediated phagocytosis of cancer cells by M1 macrophages have been realized. These results indicate that our probes should hold great potential for imaging applications in cancer immunotherapy studies and relevant anti-cancer drug screening.
关键词： fluorescent NO probes,Bodipy dye,cancer immunotherapy,NO detection,macrophage polarization
更新于2025-09-19 17:15:36
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Laser interstitial thermal therapy in gliomas
摘要： Laser interstitial thermal therapy (LITT) has been used for brain metastasis, epilepsy, and necrosis, as well as gliomas as a minimally invasive treatment for many years. With the improvement of the thermal monitoring and ablation precision, especially the application of magnetic resonance (MR) thermography in the procedure and the available of two commercial laser systems nowadays, LITT is gradually accepted by more neurosurgical centers. Recently, some new concepts, for example the adjuvant chemotherapy or radiation following LITT, the combination of immunotherapy and LITT regarding the glioma treatment are proposed and currently being investigated. The aim of this study is to summarize the evolution of LITT especially for brain gliomas and a possible outlook of the future.
关键词： gliomas,immunotherapy,blood brain barrier,Laser interstitial thermal therapy
更新于2025-09-16 10:30:52
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Plasmonic gold nanostar-mediated photothermal immunotherapy for brain tumor ablation and immunologic memory
摘要： Brain tumors present unique therapeutic challenges and they include glioblastoma (GBM) and metastases from cancers of other organs. Current treatment options are limited and include surgical resection, radiation therapy, laser interstitial thermal therapy and chemotherapy. Although much research has been done on the development of immune-based treatment platforms, only limited success has been demonstrated. Herein, we demonstrate a novel treatment of GBM through the use of plasmonic gold nanostars (GNS) as photothermal inducers for synergistic immuno photothermal nanotherapy (SYMPHONY), which combines treatments using gold nanostar and laser-induced photothermal therapy with checkpoint blockade immunotherapy. In the treatment of a murine flank tumor model with the CT-2A glioma cell line, SYMPHONY demonstrated the capability of producing long-term survivors that rejects rechallenge with cancer cells, heralding the successful emergence of immunologic memory. This study is the first to investigate the use of this novel therapy for the treatment of GBM in a murine model.
关键词： gold nanostars,cancer immunology,immunotherapy,cancer vaccines,photothermal therapy,glioblastoma
更新于2025-09-12 10:27:22
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Cerenkov Luminescence-Induced NO Release from 32P-Labeled ZnFe(CN)5NO Nanosheets to Enhance Radioisotope-Immunotherapy
摘要： The combination of radiotherapy with immunotherapy has emerged as a promising combinational therapeutic methodology. The efficacies of both types of therapies, however, are hampered by the abnormal tumor microenvironment (TME) with hypoxic and immunosuppressive features. Herein, we discover that by mixing zinc ions with sodium nitroprusside, a clinical anti-hypertensive drug, ZnFe(CN)5NO single-layer nanosheets can be obtained. Interestingly, after being labeled with 32P by simple mixing, the 32P-induced Cerenkov luminescence stimulated persistent release of NO from nanosheets. Owing to the modulation of hypoxic immunosuppressive TME by NO, such 32P-labeled nanosheets are able to completely eliminate local tumors after local administration, and proffer a strong abscopal effect after being combined with immune-checkpoint blockade therapy. Our work presents a unique 2D nanoplatform comprising Zn2+ and a clinical drug to enable chelator-free radiolabeling, Cerenkov luminescence-triggered NO release, effective TME modulation, and enhanced combination radioisotope-immunotherapy are promising for tumor metastasis treatment.
关键词： radioisotope-immunotherapy,ZnFe(CN)5NO nanosheets,Cerenkov luminescence,tumor microenvironment,NO release
更新于2025-09-12 10:27:22
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Quantum‐Chemical Evaluation of Impact of Chlorination versus Fluorination on the Electronic Properties of Donors and Acceptors for Organic Solar Cells
摘要： Lung cancer is one of the most prevalent and fatal cancer worldwide. The traditional treatments including surgery, radiotherapy, chemotherapy and targeted therapy are not satisfactory because of severe side effects and/or relapse. Genetically engineered T-cell–based immunotherapy for malignant cancer shows promise in recent clinical trials. T-cell receptor (TCR)-engineered T cells targeting New York esophageal squamous cell carcinoma 1 (NY-ESO-1) have been employed in a number of clinical trials for late stage melanoma, synovial sarcoma, multiple myeloma and other malignancies. Owing to the significant efficacy and controllable side effect, NY-ESO-1 has been considered as one of the most ideal TCR-engineered T cell therapy (TCR-T) cell target for solid tumors, including nonsmall cell lung cancer (NSCLC). However, the incidence of NY-ESO-1 expression and its relationship with immunosuppressive microenvironment of NSCLC are largely unclear. In this study, we analyzed the expression of NY-ESO-1 and two key immune regulators, Forkhead box P3 (Foxp3) and indoleamine-2,3-dioxygenase (IDO), in 156 NSCLC specimens by immunohistochemistry. Our results showed that NY-ESO-1 positive rate is 28.1% (44/156) and significantly higher in distal metastasis (P = 0.012) and late stage (P = 0.019) NSCLC patients. In addition, we found that NY-ESO-1 expression was positively associated with Foxp3 level but not IDO. These findings implied the potential role of NY-ESO-1 in tumor immune escape of NSCLC and indicated the requirement to remove Treg cells in TCR-T cell therapy for NSCLC patients.
关键词： NY-ESO-1,Foxp3,nonsmall cell lung cancer,IDO,immunotherapy
更新于2025-09-11 14:15:04