Tumor-mediated shape-transformable nanogels with pH/redox/enzymatic-sensitivity for anticancer therapy

Background: Delivery of anticancer drug(s) throughout tumor tissues is critical for cancer therapy. However, most current nanomedicines lack sufficient tumor permeability due to their bulky size (100 ~ 200 nm), which is a main reason for clinical failure in tumor chemotherapy up to now. Results: To overcome this challenge, we developed a kind of tumor-mediated transformable chitosan-based nanocarriers with surface-charge adjustability via self-assembly and double-crosslinking approach. Their surface-charge variation allowed for selective administration of drugs of specific charges. The nanomedicine maintained good colloidal stability, and upon arrival under the reducible and lysozyme-expressed microenvironments mimicking tumor tissues, one nanomedicine was cleaved to release around one thousand ultrasmall nanovesicles (4 ± 1 nm). This size transformability allowed for their passing through the depth of solid tumor tissues to achieve an effective therapeutic delivery into cancer cells to enhance antitumor efficacy, suggesting its potential use as a platform for therapeutic delivery. Conclusions: Our work provide a strategy to develop tumor-stimulative shape-transformable nanoplatform for anticancer drug delivery.