Abstract
Acidic tumor microenvironment has been extensively explored to design pH-responsive paclitaxel prodrug micelles for cancer therapy. The object of this study is to investigate the pH-responsive drug release behavior and the anti-proliferation capacity of acetal-linked paclitaxel polymeric prodrug micelles. The prodrug was synthesized and evaluated for paclitaxel content. The prodrug micelles were fabricated and characterized for morphology, size, in vitro pH-responsive paclitaxel release, cellular uptake, and anti-proliferation. Paclitaxel content was 33 wt%. The prodrug micelles exhibited spherical structure with the hydrodynamic diameter of 154 nm. Besides, the in vitro paclitaxel release behavior was verified to be pH-responsive, and 77%, 38%, and 17% of parent free paclitaxel was released from the nano-sized prodrug micelles in 13 h at pH 5.5, 6.5, and 7.4, respectively. The cellular uptake assessment demonstrated the time-dependent internalization of prodrug micelles. Meanwhile, CCK-8 analysis showed that prodrug micelles possessed the potent anti-proliferation effects. Prodrug micelles based on aliphatic polycarbonates present a promising platform for cancer chemotherapy due to the pH-responsive characteristics of acetal bond, potent anti-proliferation effects, and outstanding cytocompatibility of aliphatic polycarbonates.
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