Combination of a STING Agonist and Photothermal Therapy Using Chitosan Hydrogels for Cancer Immunotherapy.

Cyclic dinucleotides (CDNs) are a promising class of immune agonists that trigger the stimulator of interferon genes (STING) to activate both innate and acquired immunity. However, the efficacy of CDNs is limited by drug delivery barriers. Therefore, we developed a combined immunotherapy strategy based on injectable reactive oxygen species (ROS)-responsive hydrogels, which sustainably release 5,6-dimethylxanthenone-4-acetic acid (DMXAA) as known as a STING agonist and indocyanine green (ICG) by utilizing a high level of ROS in the tumor microenvironment (TME). The STING agonist combined with photothermal therapy (PTT) can improve the biological efficacy of DMXAA, transform the immunosuppressive TME into an immunogenic and tumoricidal microenvironment, and completely kill tumor cells. In addition, this bioreactive gel can effectively leverage local ROS to facilitate the release of immunotherapy drugs, thereby enhancing the efficacy of combination therapy, improving the TME, inhibiting tumor growth, inducing memory immunity, and protecting against tumor rechallenge.

Injectable and Biodegradable Chitosan Hydrogel-Based Drug Depot Contributes to Synergistic Treatment of Tumors.

Combined therapy provides a more effective method in the treatment of tumors and becomes a research hotspot. To improve treatment outcomes and reduce serious side effects, hydrogel-based local delivery was developed herein to form a drug depot in suit to eliminate tumors. Indocyanine green and imiquimod were coencapsulated in the novel temperature-sensitive chitosan hydrogel. After intratumoral injection of the hydrogel, indocyanine green that accumulated in the tumor area could induce thermal ablation of primary tumors under laser irradiation. In the presence of imiquimod, the immune effects increased the probability of complete ablation of primary tumors and inhibition of metastases. Combined with cyclophosphamide, the enhanced immunological responses would further inhibit tumors and prolong the survival time. In a word, this work offered an excellent local delivery platform that enabled a remarkable combined antitumor strategy and achieved synergistic therapeutic effects.

The role of FOS-mediated autophagy activation in the indocyanine green-based photodynamic therapy for treating melanoma.

The morbidity and mortality of melanoma which accounts for 90% of cutaneous neoplasm-related deaths is growing over the last few decades. Common treatments for melanoma are limited to poor tissue selectivity, high toxicity and drug resistance. Photodynamic therapy (PDT) is an effective adjuvant therapy and could be a promising therapy for melanoma. Multiple mechanisms are involved in PDT2 and programmed cell death (PCD) which comprises of autophagy and apoptosis is likely to be a critical one. Whereas, the molecular mechanism and subsequent effect of PDT-induced autophagy in melanoma are still unclear. In this study, we first analyzed gene expression data in the TCGA3 and GEO4 databases to clarify that PDT-induced-autophagy improved the prognosis of melanoma. The expression of FOS which generally defined as an immediate-early gene (IEG) and related to cell autophagy was found significantly elevated after PDT. To further investigate whether FOS played a key role in PDT-induced-autophagy of melanoma, we first determined the optimum concentration of ICG solution for autophagy observation. Then, relative FOS expression was detected at mRNA and protein level and cell autophagy was observed by western blot and flow cytometry. We found that ICG-PDT treatment could significantly elevate FOS expression in SKCM5 B16 cells, and FOS promoted ICG-PDT-induced cell autophagy. To sum up, our data indicated that FOS was involved in ICG-PDT-induced-autophagy in melanoma and furthermore improved the prognosis of melanoma.

Gold-Nanobipyramid-Based Nanotheranostics for Dual-Modality Imaging-Guided Phototherapy.

Multimodality imaging-guided therapy can improve the diagnostics and therapeutics efficiency of cancer. Herein, we developed a light-responsive nanotheranostic agent based on the indocyanine green (ICG) conjugated mesoporous silica coated gold nanobipyramid (GNB@SiO2) (denoted as GNB@SiO2-ICG) for simultaneous fluorescence (FL)/photoacoustic (PA) imaging-guided photothermal therapy (PTT). The GNB@SiO2 with excellent photostability was used for PA imaging as well as PTT. The loaded ICG promised FL imaging and PTT. The feasibility of the cancer theranostic capability of GNB@SiO2-ICG was evaluated from cancer cells to mice. Under the guidance of FL/PA imaging, GNB@SiO2-ICG exhibited remarkably enhanced therapeutic efficacy, which could eliminate the tumor tissues completely without tumor recurrence. This well-defined nanotheranostic nanoplatform that intelligently integrates dual-modality imaging and phototherapy provides an efficient nanoplatform for cancer nanotheranostics.

Light-Responsive Biodegradable Nanorattles for Cancer Theranostics.

Cancer nanotheranostics, integrating both diagnostic and therapeutic functions into nanoscale agents, are advanced solutions for cancer management. Herein, a light-responsive biodegradable nanorattle-based perfluoropentane-(PFP)-filled mesoporous-silica-film-coated gold nanorod (GNR@SiO2 -PFP) is strategically designed and prepared for enhanced ultrasound (US)/photoacoustic (PA) dual-modality imaging guided photothermal therapy of melanoma. The as-prepared nanorattles are composed of a thin mesoporous silica film as the shell, which endows the nanoplatform with flexible morphology and excellent biodegradability, as well as large cavity for PFP filling. Upon 808 nm laser irradiation, the loaded PFP will undergo a liquid-gas phase transition due to the heat generation from GNRs, thus generating nanobubbles followed by the coalescence into microbubbles. The conversion of nanobubbles to microbubbles can improve the intratumoral permeation and retention in nonmicrovascular tissue, as well as enhance the tumor-targeted US imaging signals. This nanotheranostic platform exhibits excellent biocompatibility and biodegradability, distinct gas bubbling phenomenon, good US/PA imaging contrast, and remarkable photothermal efficiency. The results demonstrate that the GNR@SiO2 -PFP nanorattles hold great potential for cancer nanotheranostics.