Tumor targeting effects of a novel modified paclitaxel-loaded discoidal mimic high density lipoproteins.

Objective: Monocholesterylsuccinate (CHS)-modified paclitaxel-loaded discoidal reconstituted high density lipoproteins (cP-d-gamma HDL) as novel biomimetic nanocarriers that were developed for tumor targeting delivery to avoid unexpected drug leakage from discoidal reconstituted high density lipoproteins (d-gamma HDL) during remodeling process associated with lecithin-cholesterol acyltransferase (LCAT). Methods: Their in vitro characterizations and biomimetic properties, simultaneously tumor distribution and pharmacodynamics in tumor bearing mice were elaborately investigated. Results: In vitro characterization results showed that cP-d-gamma HDL had nano-size diameter, high negative zeta potential and high entrapment efficiency (EE). Furthermore, morphology study indicated that cP-d-gamma HDL did not remodel in the presence of LCAT, compared with that of paclitaxel-loaded d-gamma HDL (P-d-gamma HDL, not modified). And cellular uptake, together with cytotoxicity toward tumor cells of cP-d-gamma HDL was not affected after interaction with LCAT. Tumor distribution and pharmacodynamics tests revealed that cP-d-gamma HDL possessed specific targeting property and anti-tumor efficacy. Conclusion: cP-d-gamma HDL served to restrain remodeling process and drug leakage, at the same time reinforce the targeting effect, and could act as a potential drug delivery system for cancer therapy.