Oligolactic Acid Prodrug-Based Nanomedicines for Cancer Therapy

Grant information

The Kwon Research develops oligo(lactic acid) (o(LA)) prodrugs, such as o(LA)₈-paclitaxel (PTX), encapsulated in poly(ethylene glycol)-block-poly(lactic acid) (PEG-b-PLA) micelles to enhance drug delivery for triple-negative breast cancer (TNBC). o(LA)₈-PTX prodrug-loaded PEG-b-PLA micelles achieve high drug loading (up to 50% w/w), prolonged plasma exposure (2-3× higher AUC than non-prodrug formulations), and delayed release, which prolongs tumor exposure and targets cancer cells during vulnerable cell cycle phases. In a murine 4T1 model, o(LA)₈-PTX demonstrated superior antitumor efficacy over conventional PTX formulations, reducing toxicity while maintaining potency. Pharmacokinetic studies in rats revealed o(LA)₁-PTX as the dominant bioactive metabolite. We explore combination therapies, co-loading PTX prodrugs with signal inhibitors (e.g., rapamycin, selumetinib) in PEG-b-PLA micelles to achieve synergistic effects in TNBC. Scale-up efforts aim to transition these nanomedicines to clinical use, emphasizing simplified manufacturing and improved safety profiles. Future directions include optimizing multidrug ratios for enhanced synergy and advancing clinical translation of these theranostic platforms.