1. Academic Validation
  2. Toolbox of Biodegradable Dendritic (Poly glycerol sulfate)-SS-poly(ester) Micelles for Cancer Treatment: Stability, Drug Release, and Tumor Targeting

Toolbox of Biodegradable Dendritic (Poly glycerol sulfate)-SS-poly(ester) Micelles for Cancer Treatment: Stability, Drug Release, and Tumor Targeting

  • Biomacromolecules. 2021 Jun 14;22(6):2625-2640. doi: 10.1021/acs.biomac.1c00333.
Daniel Braatz 1 Mathias Dimde 1 Guoxin Ma 1 Yinan Zhong 2 Michael Tully 1 Carsten Grötzinger 3 4 Yuanyuan Zhang 2 Alexandros Mavroskoufis 1 Michael Schirner 1 Zhiyuan Zhong 5 Matthias Ballauff 1 Rainer Haag 1
Affiliations

Affiliations

  • 1 Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany.
  • 2 Department of Pharmaceutical Engineering, China Pharmaceutical University, Nanjing 211198, P. R. China.
  • 3 Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
  • 4 German Cancer Consortium (DKTK), Partner Site Berlin, 13353 Berlin, Germany.
  • 5 Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, and State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123, P. R. China.
Abstract

In this paper, we present well-defined dPGS-SS-PCL/PLGA/PLA micellar systems demonstrating excellent capabilities as a drug delivery platform in LIGHT of high stability and precise in vitro and in vivo drug release combined with active targetability to tumors. These six amphiphilic block copolymers were each targeted in two different molecular weights (8 or 16 kDa) and characterized using 1H NMR, gel permeation chromatography (GPC), and elemental analysis. The block copolymer micelles showed monodispersed size distributions of 81-187 nm, strong negative charges between -52 and -41 mV, and low critical micelle concentrations (CMCs) of up to 1.13-3.58 mg/L (134-527 nM). The serum stability was determined as 94% after 24 h. The drug-loading efficiency for Sunitinib ranges from 38 to 83% (8-17 wt %). The release was selectively triggered by glutathione (GSH) and Lipase, reaching 85% after 5 days, while only 20% leaching was observed under physiological conditions. Both the in vitro and in vivo studies showed sustained release of Sunitinib over 1 week. CCK-8 assays on HeLa lines demonstrated the high cell compatibility (1 mg/mL, 94% cell viability, 48 h) and the high Cancer cell toxicity of Sunitinib-loaded micelles (IC50 2.5 μg/mL). By in vivo fluorescence imaging studies on HT-29 tumor-bearing mice, the targetability of dPGS7.8-SS-PCL7.8 enabled substantial accumulation in tumor tissue compared to nonsulfated dPG3.9-SS-PCL7.8. As a proof of concept, Sunitinib-loaded dPGS-SS-poly(ester) micelles improved the antitumor efficacy of the chemotherapeutic. A tenfold lower dosage of loaded Sunitinib led to an even higher tumor growth inhibition compared to the free drug, as demonstrated in a HeLa human cervical tumor-bearing mice model. No toxicity for the organism was observed, confirming the good biocompatibility of the system.

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