Enhanced Endocytic and pH-Sensitive Poly(malic acid) Micelles for Antitumor Drug Delivery
Poly(β-benzyl malate) (PBM), a derivative of poly(β-malic acid) (PMLA), is a potential antitumor drug carrier due to its desirable biocompatibility and nontoxicity. In this study, micelles based on PBM-PEG polymers were prepared, which possessed several key features, including (i) micelle formation via self-assembly with a size of approximately 100 nm, (ii) π–π stacking interactions between the polymer chains and between the polymer and the drug, improving the stability of micelles and drug loading capacity (drug loading rate increased to 20 wt%), (iii) the cell penetrating peptide (TAT) was shielded by a long PEG chain before reaching the tumor site and exposed to tumor tissue, and (iv) high efficiency tumor uptake via exposure to TAT. At the site of a tumor, the extracellular pH level caused cleavage of the hydrazine bond, which led to the exposure of TAT on the polymeric micelles, thus enhancing cellular internalization. Then, the polymeric micelles disintegrated and DOX was released in response to the acidic pH in the lysosomal and endosomal compartments within the tumor cells. Both in vitro and in vivo efficacy studies indicated that this pH-sensitive PBM polymeric micelle is a promising antitumor drug carrier.
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Document Type: Research Article
Publication date: January 1, 2019
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