A dextran–platinum(iv) conjugate as a reduction-responsive carrier for triggered drug release. Issue 41 (21st September 2015)

• Record Type: Journal Article
• Authors: He, Shasha; Cong, Yuwei; Zhou, Dongfang; Li, Jizhen; Xie, Zhigang; Chen, Xuesi; Jing, Xiabin; Huang, Yubin
• Is Part Of: Journal of materials chemistry. Volume 3:Issue 41(2015)
• Page Start: 8203
• Page End: 8211
• Publication Date: 2015-09-21
• Subjects: Materials -- Periodicals; Chemistry, Analytic -- Periodicals; Biomedical materials -- Research -- Periodicals; 543.0284
• DOI: 10.1039/c5tb01496d
• Languages: English
• ISSNs: 2050-750X

Abstract

Abstract : An amphiphilic dextran–Pt(iv ) conjugate was constructed by conjugation of a hydrophobic Pt(iv ) prodrug to the side chains of hydrophilic dextran. The conjugate could self-assemble into stable nanoparticle as a reduction-responsive carrier for DOX encapsulation and triggered release. Abstract : Reduction-responsive nano-carriers have been confirmed to be promising for intracellular drug delivery. To develop multifunctional polymer-based drug delivery system, a novel dextran–Pt(iv ) conjugate was synthesized by conjugating Pt(iv ) to the side chains of the hydrophilic dextran and used for doxorubicin (DOX) delivery. Pt(iv ) conjugation could change the hydrophilicity of dextran, leading to the self-assembly of dextran–Pt(iv ) conjugates with different morphologies. Pt(iv ) segments served as the key components in assembly formation and as the antitumor prodrug. Under a reductive environment, Pt(iv ) was found to be reduced to its active Pt(ii ) form and cleaved from dextran, shifting the hydrophilic–hydrophobic balance of the dextran–Pt(iv ) conjugate. The collapse of the assembly structure due to the partial or complete recovery of the hydrophilicity of dextran led to triggered release of DOX. The DOX-loaded dextran–Pt(iv ) conjugate obtained by combining the released hydrophobic DOX and recovered hydrophilic Pt(ii ), was found to be very effective as an antitumor agent as demonstrated in in vitro cytotoxicity evaluations. This DOX-loaded dextran–Pt(iv ) conjugate system provided a new strategy to trigger the release of hydrophobic and hydrophilic drugs at the same time via single reduction-responsive control to provide an enhanced anti-tumor effect.