Establishment of Facile Nanomedicine Construction Methodology to Comprehensively Overcome Hurdles across Tumor-Specific Nano-Delivery
To advance clinical translation of antitumor nanomedicines, the development of a universally applicable, facile, and safe methodology for nanomedicine construction to overcome major hurdles across tumor-specific nano-delivery in an all-in-one manner would be highly desirable. This study puts forward a HAylation strategy based on positively charged nanocore (NC + ) and hyaluronic acid (HA) that is naturally present in the human body. HAylation leads to prolonged blood duration and active tumor targeting. It is demonstrated that HAylation facilitates not only selective uptake of nanomedicines by tumor cells but also deep tumor infiltration via the special transcytosis pathway. This characteristic is ascribed to the site-specific exposure of NC + in tumor cells due to fast HA degradation exclusively in response to HAase and an acidic pH in the lysosome after tumor accumulation. HAylation enables the free construction of a NC + nano-core with versatile functions. Here, a NC + core is fabricated by directly assembling a photodynamic therapy (PDT) agent and an inhibitor of the DNA base excision repair (BER) pathway. The inhibition of BER-mediated DNA repair has proven powerful to amplify antitumor efficacy since DNA damage is one major cell-killing mechanism for many anticancer therapeutics. HAylation holds promise for the simplification of the industrial production of nanomedicines and arms nanomedicines to thoroughly overcome fundamental nano-delivery hurdles.
危险品化学品经营许可证（带存储）