期刊
DRUG DELIVERY
卷 28, 期 1, 页码 195-205出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/10717544.2020.1870583
关键词
Ursolic acid; redox-responsive; pH-responsive; polymeric prodrug; micelles; osteosarcoma
A redox-sensitive UA polymeric prodrug formulation was synthesized to significantly prolong circulation in blood, favor accumulation in tumor tissue, and achieve potent antitumor efficacy.
Ursolic acid (UA), found widely in nature, exerts effective anti-tumoral activity against various malignant tumors. However, the low water solubility and poor bioavailability of UA have greatly hindered its translation to the clinic. To overcome these drawbacks, a simple redox-sensitive UA polymeric prodrug was synthesized by conjugating UA to polyethylene glycol using a disulfide bond. This formulation can self-assemble into micelles (U-SS-M) in aqueous solutions to produce small size micelles (similar to 62.5 nm in diameter) with high drug loading efficiency (similar to 16.7%) that exhibit pH and reduction dual-sensitivity. The cell and animal studies performed using the osteosarcoma MG-63 cell line and MG-63 cancer xenograft mice as the model systems consistently confirmed that the U-SS-M formulation could significantly prolong the circulation in blood and favor accumulation in tumor tissue. Targeted accumulation allows the U-SS-M to be effectively internalized by cancer cells, where the rapid release of UA is favored by a glutathione-rich and acidic intracellular environment, and ultimately achieves potent antitumor efficacy.
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