Intelligent nanogels with self-adaptive responsiveness for improved tumor drug delivery and augmented chemotherapy

For cancer nanomedicine, the main goal is to deliver therapeutic agents effectively to solid tumors. Here, we report the unique design of self-adaptive ultrafast charge-reversible chitosan-polypyrrole nanogels (CH-PPy NGs) for enhanced tumor delivery and augmented chemotherapy. CH was first grafted with PPy to form CH-PPy polymers that were used to form CH-PPy NGs through glutaraldehyde cross-linking via a miniemulsion method. The CH-PPy NGs could be finely treated with an alkaline solution to generate ultrafast charge-reversible CH-PPy-OH-4 NGs (R-NGs) with a negative charge at a physiological pH and a positive charge at a slightly acidic pH. The R-NGs display good cytocompatibility, excellent protein resistance, and high doxorubicin (DOX) loading efficiency. Encouragingly, the prepared R-NGs/DOX have prolonged blood circulation time, enhanced tumor accumulation, penetration and tumor cell uptake due to their self-adaptive charge switching to be positively charged, and responsive drug delivery for augmented chemotherapy of ovarian carcinoma in vivo. Notably, the tumor accumulation of R-NGs/DOX (around 4.7%) is much higher than the average tumor accumulation of other nanocarriers (less than 1%) reported elsewhere. The developed self-adaptive PPy-grafted CH NGs represent one of the advanced designs of nanomedicine that could be used for augmented antitumor therapy with low side effects.