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Colloidal hydroxyethyl starch for tumor-targeted platinum delivery

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Abstract

Cis-platinum has been widely used as a first-line chemotherapy agent in clinics for more than 40 years. Although considerable efforts have been expended for developing platinum-based nano drug delivery systems (NDDS) to resolve the problems of low water solubility, short half-life, and severe side effects of cis-platinum, it remains challenging to apply these nanoplatforms to cancer treatments in clinics on account of the issues related to safety, complex fabrication procedures, and limited cellular uptake. Herein, we constructed a novel cis-platinum delivery system with hydroxyethyl starch (HES), which is a semisynthetic polysaccharide that has been used worldwide as colloidal plasma volume expanders (PVE) in clinics for several decades. By combining TEM, AFM, and DLS, we have found that HES particles are colloidal nanoparticles in solution, with diameters ranging from 15 to 40 nm as a function of molecular weight. We further revealed that HES adopted a hyperbranched colloidal structure with rather compact conformation. These results demonstrate that HES is a promising nanocarrier to deliver drug molecules. Taking advantage of the poly-hydroxyl sites of HES, we constructed a novel HES-based cis-platinum delivery nanoplatform. HES was directly conjugated with cis-platinum prodrug via an ester bond and decorated with an active targeting molecule, lactobionic acid (LA), contributing toward higher in vitro antitumor activity against hepatoma carcinoma cells as compared to cis-platinum. These results have significant implications for the clinically used plasma volume expander-HES and shed light on the clinical translation of HES-based nano drug delivery systems.

Graphical abstract: Colloidal hydroxyethyl starch for tumor-targeted platinum delivery

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Publication details

The article was received on 05 Oct 2018, accepted on 23 Nov 2018 and first published on 26 Nov 2018


Article type: Paper
DOI: 10.1039/C8NA00271A
Citation: Nanoscale Adv., 2019, Advance Article
  • Open access: Creative Commons BY-NC license
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    Colloidal hydroxyethyl starch for tumor-targeted platinum delivery

    C. Xiao, H. Hu, H. Yang, S. Li, H. Zhou, J. Ruan, Y. Zhu, X. Yang and Z. Li, Nanoscale Adv., 2019, Advance Article , DOI: 10.1039/C8NA00271A

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