A novel self-assembled nanoparticle platform based on pectin-eight-arm polyethylene glycol-drug conjugates for co-delivery of anticancer drugs

Highlights: • The synthesis of Pec-8armPEG-UA conjugate and Pec-PEG-UA conjugate • Preparation of Pec-8PUH NPs and Pec-PUH NPs • In vitro and in vivo antitumor activities of Pec-8PUH NPs and Pec-PUH NPs were investigated. - Abstract: The application of non-toxic carriers to increase drug loading, multi-drug delivery, and extremely small size of nano-drugs to construct a tremendous transmission system is the goal for all researchers to be pursued. The proposal of natural pectin nano-platform for delivery of multiple drugs is critical for biomedical research, especially a particle size of below 100 nm with high yield. Here we design a new core-shell structure pectin-eight-arm polyethylene glycol-ursolic acid/hydrooxycampothecin nanoparticle (Pec-8PUH NPs) through a special self-assembly method for stabilizing and dispersing particles, improving water-solubility, and achieving drug controlled release. The obtained Pec-8PUH NPs possessed appropriate size (~ 91 nm), drug-loaded efficiency and encapsulation efficiency through the regulation of eight-arm polyethylene glycol. In addition, Pec-8PUH NPs could enhance cell cytotoxicity, shorten blood retention time (7.3-fold UA, 7.2-fold HCPT) and more effective cellular uptake than free drugs, which exhibited an obvious synergistic effect of UA and HCPT by the co-delivery. 4T1 tumor-bearing mice also showed a higher survival rate than free UA and free HCPT. The result further shows that this novel drug delivery system has a promising potential for anti-cancer combination therapy.