Enzyme- and pH-Sensitive Branched Polymer–Doxorubicin Conjugate-Based Nanoscale Drug Delivery System for Cancer Therapy

• DOI: 10.1021/acsami.6b02006
• Publication Date: 2016-04-22T10:11:28Z
• Authors: Xiaoli Wei; Qiang Luo; Ling Sun; Xue Li; Hongyan Zhu; Pujun Guan; Min Wu; Kui Luo; Qiyong Gong
• Keywords: Conjugate; Cancer Therapy

Owing to their dendritic architectural features, branched copolymers have been investigated as drug delivery systems. In this paper, an enzyme- and pH-sensitive poly[N-(2-hydroxypropyl)methacrylamide] (polyHPMA) copolymer–doxorubicin (DOX) conjugate possessing a molecular weight (MW) of 165 kDa was designed prepared via one-pot reaction conjugation. This conjugate's potential smart, nanoscale system (NDDS) is also investigated. The capable forming nanoparticles with negative surface charge. self-assembled were 102 nm in diameter measured by dynamic light scattering (DLS) 95 scanning electron microscopy, respectively. degraded low-MW products (23∼25 kDa) the presence papain or cathepsin B, degradation monitored DLS size-exclusion chromatography. demonstrated release, DOX attached copolymer hydrazone bond. comparison free DOX, conjugate-based exhibited greater accumulation breast tumors, resulting enhanced antitumor therapeutic indexes. Furthermore, widespread dissemination among tumor cells confirmed immunohistochemical assay. Finally, no obvious systemic toxicities observed vivo normal mice. Thus, HPMA copolymer–DOX may be employed safe efficient pH- enzyme-responsive NDDS for cancer therapy.