多功能生物可降解聚合物纳米药物载体:设计合成及在肿瘤靶向治疗上的应用

Biodegradable polymeric nanocarriers have emerged as one of the most promising platforms for targeted tumor therapy owing to their excellent biocompatibility, prolonged circulation time, enhanced accumulation in tumors, and in vivo biodegradability. Remarkably, several anticancer nanomedicines based on biodegradable polymeric nanocarriers showed clear advantages, including decreased side effects and improved drug tolerance, and have advanced to clinical practices or clinical trials. However, the therapeutic outcomes are far from optimal, owing to poor in vivo stability, low tumor targetability, inefficient cellular uptake, and slow intracellular drug release, etc. Thus, the development of new strategies to improve the therapeutic efficiency of polymeric nanomedicines is of great interest. This review highlights the recent developments made by our group and others in multifunctional biodegradable polymeric nanocarriers for safe and efficient cancer chemotherapy. In particular, we will present the following four polymeric nanoscale systems: (i) chemically or physically crosslinked biodegradable polymeric nanocarriers that display markedly improved stability and tumor targetability while prohibiting drug leakage; (ii) bio-responsive, biodegradable polymeric nanocarriers that enhance tumor cell uptake via reversal of the stealth effect in response to the tumor microenvironment or rapidly and efficiently releasing drugs into the tumor tissue and/or inside the tumor cells; (iii) stimuli-responsive crosslinked biodegradable polymeric nanocarriers that elegantly address the extracellular stability and intracellular drug release dilemma; and (iv) tumor-targeted biodegradable polymeric nanocarriers that enhance drug retention in the tumor and facilitate tumor cell uptake of nanomedicines. Finally, the pros and cons of current multifunctional polymeric nanosystems are discussed. We are convinced that, with rationale design, precision preparation, and systemic research and development, various multifunctional polymeric nanoparticulate drugs will soon advance to clinical settings and play an indispensable role in targeted cancer therapy.