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.