Bioresponsive Polymeric Nanoparticles: From Design, Targeted Therapy to Cancer Immunotherapy.

Bioresponsive polymeric nanoparticles (NPs) that are capable of delivering and releasing therapeutics and biotherapeutics to target sites have attracted vivid interest in cancer therapy and immunotherapy. In contrast to enthusiastic evolution in the academic world, the clinical translation of these smart systems is scarce, partly due to concerns about safety, stability, complexity, and scalability. The moderate targetability, responsivity, and benefits are other concerns. In the past 17 years, we have devoted ourselves to exploring elegant strategies to address the above basic and translational problems by introducing diverse functional groups and/or targeting ligands to safe biomedical materials, such as biodegradable polymers and water-soluble polymers. This minimal modification is critical for further clinical translation. We have tailor-made various bioresponsive NPs including shell-sheddable and/or acid-sensitive biodegradable NPs, disulfide-cross-linked biodegradable micelles and polymersomes, and blood-brain barrier (BBB)-permeable NPs, to target different tumors. This perspective provides an overview of our work path toward targeted nanomedicines and personalized vaccines, which might inspire clinical translation and future research on cancer therapy.