Recently, Professor Liu Dongfei's team from the School of Pharmacy at our university published a research paper titled “Programmable Nanostructure Assembly of a Paclitaxel Derivative Enables Tunable Anticancer Therapy via Hydrogen Bond Engineering” in the top-tier journal ACS Nano. Ph.D. candidates Feng Guobing, Tang Hui, and undergraduate student Xie Shuyi from the School of Pharmacy are co-first authors of the paper. Ph.D. candidate Wu Tongyu is a major contributor, with China Pharmaceutical University listed as the first corresponding institution.
The morphology of drug delivery systems directly determines their in vivo fate and release behavior, thereby influencing therapeutic efficacy and safety. Precisely controlling the morphology of drug delivery systems is therefore crucial for optimizing drug behavior within the body. Different pathological microenvironments demand distinct morphologies: certain diseases favor elongated structures to enhance tissue penetration and retention, while others require dense particles to improve cellular uptake. For “one drug, multiple diseases” applications, achieving on-demand morphology switching on a single compound remains particularly challenging. Among numerous noncovalent interactions, hydrogen bonds—with their moderate strength and ubiquity—can efficiently drive molecular self-assembly and precisely regulate morphology.
Addressing this challenge, Professor Liu Dongfei's team used paclitaxel, a structurally complex natural product with potent antitumor activity, as a model to explore hydrogen bond-driven programmable morphological assembly. The team designed and synthesized amphiphilic phosphorated taxol derivatives (PTP), enhancing hydrogen bonding through hydrophilic phosphate groups to self-assemble into nanofibers. Further co-assembly with polyethylene glycol 400 (PEG400) or hyaluronic acid (HA) yielded spherical nanoparticles (PTP@PEG) and fiber bundles (PTP@HA), respectively, enabling on-demand functional allocation for delivery. In 4T1 breast cancer mice, intravenous PTP@PEG significantly prolonged systemic circulation, reduced renal accumulation, and enhanced antitumor efficacy. In a colorectal cancer peritoneal metastasis model, intraperitoneal PTP@HA demonstrated sustained release and achieved favorable therapeutic outcomes. This study systematically demonstrates precise control of drug assembly morphology through hydrogen bond regulation, providing a universal approach for effective delivery of single drugs across diverse disease scenarios.
This work was supported by the National Natural Science Foundation of China, the Jiangsu Provincial Outstanding Youth Fund, the State Key Laboratory of Bioactive Components and Efficacy of Natural Medicines, and the UMCG Research Fund.
Article link: https://pubs.acs.org/doi/10.1021/acsnano.5c10267
Figure 1: Schematic Diagram of Key Findings Summary
