Nanosized drug delivery systems modulate the immunosuppressive microenvironment to improve cancer immunotherapy.

Immunotherapy that activates immune systems for combating cancer has yielded considerable clinical benefits recently. However, the immunosuppressive tumor microenvironment (ITME) is a major hurdle to immunotherapy as it supports tumor to evade immune surveillance. Reversing ITME facilitates the recruitment and activation of antitumor immune cells, thereby promoting immunotherapy. Our group has developed various nanosized drug delivery systems (NDDSs) to modulate ITME with enhanced efficacy and safety. In the review we introduce the ITME-remodeling strategies for improving immunotherapy based on NDDSs including triggering tumor cells to undergo immunogenetic cell death (ICD), applying tumor vaccine, and directly regulating intratumoral immune components (immune cells or cytokines). In order to guide the design of NDDSs for amplified effects of antitumor immunotherapy, the contributions and future directions of this field are also discussed.

Author Correction: Co-delivery of docetaxel and silibinin using pH-sensitive micelles improves therapy of metastatic breast cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Co-delivery of docetaxel and silibinin using pH-sensitive micelles improves therapy of metastatic breast cancer.

Breast cancer is the most vicious killer for women, and tumor metastasis is one of the leading causes of breast cancer therapy failure. In this study, a new pH-sensitive polymer (polyethylene glycol-block-poly[(1,4-butanediol)-diacrylate-ß-N,N-diisopropylethylenediamine], BDP) was synthesized. Based on BDP, docetaxel/silibinin co-delivery micelles (DSMs) was constructed. DSM had a well-defined spherical shape under the transmission electron microscope with average hydrodynamic diameter of 85.3±0.4 nm, and were stable in the bloodstream but could dissociate to release the chemotherapeutic agents in the low pH environment of the endo/lysosomes in the tumor cells. Compared with free drugs, DSM displayed greatly enhanced cellular uptake, higher cytotoxicity and a stronger anti-metastasis effect against mouse breast cancer cell line 4T1. In 4T1 tumor-bearing mice treated with DSM (twice a week for 3 weeks), the inhibition rate on tumor growth and metastasis reached 71.9% and 80.1%, respectively. These results reveal that DSM might be a promising drug delivery system for metastatic breast cancer therapy.