Chitosan-based nano-micelles for potential anti-tumor immunotherapy: Synergistic effect of cGAS-STING signaling pathway activation and tumor antigen absorption.

Cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) signaling pathway is an essential DNA-sensing pathway to regulate the innate and adaptive immune response, which plays an important role in tumor immunotherapy. Although the STING agonists can be used, they are limited by their inability to target immune cells and systemic immunotoxicity, calling for novel strategies to accurately and effectively activate the cGAS-STING signaling pathway. Herein, mannose-modified stearic acid-grafted chitosan (M-CS-SA) micelles with the ability to activate the cGAS-STING signaling pathway and absorb tumor antigens were constructed.

Normalizing Tumor Blood Vessels to Improve Chemotherapy and Inhibit Breast Cancer Metastasis by Multifunctional Nanoparticles.

The abnormal tumor blood vessels with high leakage can promote tumor cells to infiltrate into the systemic circulation and increase the risk of tumor metastasis. In addition, chemotherapy may destroy tumor blood vessels and further aggravate metastasis. Normalizing tumor blood vessels can reduce vascular leakage and increase vascular integrity.

GSH-Responsive Polymeric Micelles for Remodeling the Tumor Microenvironment to Improve Chemotherapy and Inhibit Metastasis in Breast Cancer.

The tumor microenvironment (TME) of breast cancer is hypoxic, which can promote tumor progression, including invasion and metastasis, and limit the efficacy of anti-tumor treatment. Nitric oxide (NO) can dilate blood vessels, effectively alleviate hypoxia, and regulate the TME, which has the potential to improve the anti-tumor therapeutic efficacy. Here, chitosan (CO) and octadecylamine (ODA) were linked by the disulfide bond, and the LinTT1 peptide was linked onto CO-SS-ODA for targeting tumor cells and endothelial cells in tumors.

Combination of tumor vessel normalization and immune checkpoint blockade for breast cancer treatment multifunctional nanocomplexes.

Tumor vessel normalization can alleviate hypoxia, reduce the intratumoral infiltration of immunosuppressive cells and increase the intratumoral infiltration of immune effector cells (CD8 T cells), further reversing the immunosuppressive microenvironment. Here, nanocomplexes (lipo/St@FA-COSA/BMS-202) which can accurately deliver drugs to tumor tissues and release different drugs at different sites with different rates were prepared to combine tumor vessel normalization with immune checkpoint blockade. The results of drug release showed that in a pH 6.

Aptamer and Peptide-Modified Lipid-Based Drug Delivery Systems in Application of Combined Sequential Therapy of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is known as the most common malignancy of the hepatobiliary system with a continued increase in incidence but limited therapeutic options. Nanomedicine has provided a promising strategy through engineered nanocarriers that are capable of targeting therapeutic agents specifically to tumor cells. In this research, two aptamer/peptide-modified lipid-based drug delivery systems (A54-PEG-SLN/OXA and A15-PEG-SLN/SAL) were developed as a sequential therapeutic strategy to conquer specific hepatocellular carcinoma.

pH-Responsive Biomimetic Polymeric Micelles as Lymph Node-Targeting Vaccines for Enhanced Antitumor Immune Responses.

Lymph nodes are proposed as the intriguing target in cancer immunotherapy, and cellular immunity is vital for vaccines to fight against cancer. However, inefficient delivery of vaccines to lymph nodes and deficient lysosomal escape of antigens result in weak cellular immunity, which restrains the strength of vaccines in inducing antitumor immune responses. Hence, dendritic cell membrane (DCM)/histidine-modified stearic acid-grafted chitosan (HCtSA)/ovalbumin (OVA) micelles, as pH-responsive biomimetic vaccines, were fabricated to target lymph nodes and induce cellular immunity for enhanced antitumor immune responses.

Tumor-draining lymph node targeting chitosan micelles as antigen-capturing adjuvants for personalized immunotherapy.

Tumor-draining lymph node (TDLN), already bathed in tumor antigens, has been proposed as an intriguing site for cancer immunotherapy. Targeted delivery of adjuvants to TDLN, presumably could induce antitumor immunity for personalized immunotherapy. Although molecular adjuvants can be used for personalized immunotherapy, their efficacy is limited by insufficient antigen uptake by dendritic cells (DCs).

Selective uptake of chitosan polymeric micelles by circulating monocytes for enhanced tumor targeting.

Micelles are one of the most investigated nanocarriers for drug delivery. In this study, polymeric micelles based on chitosan were prepared to explore the delivery mechanism which was critical for enhancing tumor targeting but still remain elusive. The chitosan polymer COSA was synthesized and the polymeric micelles showed good self-assembly ability, good dispersion stability and low toxicity.