Micelles with Sheddable Dendritic Polyglycerol Sulfate Shells Show Extraordinary Tumor Targetability and Chemotherapy in Vivo
- authored by
- Yinan Zhong, Mathias Dimde, Daniel Stöbener, Fenghua Meng, Chao Deng, Zhiyuan Zhong, Rainer Haag
- Abstract
Cancer nanomedicines are typically stealthed by a poly(ethylene glycol) layer that is important to obtain extended blood circulation and elevated tumor accumulation. PEG stealth, however, also leads to poor tumor cell selectivity and uptake thereby reducing treatment efficacy. Here, we report that biodegradable micelles with sheddable dendritic polyglycerol sulfate (dPGS) shells show an unusual tumor targetability and chemotherapy in vivo. The self-assembly of dPGS-SS-poly(μ-caprolactone) amphiphilic block copolymer with an Mn of 4.8-3.7 kg mol-1 affords negatively charged and small sized micelles (dPGS-SS-PCL Ms). dPGS-SS-PCL Ms reveal a low cytotoxicity, decent doxorubicin (DOX) loading, and accelerated drug release under a reductive condition. Notably, DOX-loaded dPGS-SS-PCL Ms exhibit a high tolerable dosage of more than 40 mg kg-1, a long plasma half-life of ca. 2.8 h, and an extraordinary tumor accumulation. Intriguingly, therapeutic results demonstrate that DOX-loaded dPGS-SS-PCL Ms induce complete tumor suppression, significantly improved survival rate, and diminishing adverse effects as compared to free drug (DOX·HCl) in MCF-7 human mammary carcinoma models. Dendritic polyglycerol sulfate with a superior tumor homing ability appears to be an attractive alternative to PEG in formulating targeted cancer nanomedicines.
- External Organisation(s)
-
Soochow University
Freie Universität Berlin (FU Berlin)
- Type
- Article
- Journal
- ACS Applied Materials and Interfaces
- Volume
- 8
- Pages
- 27530-27538
- No. of pages
- 9
- ISSN
- 1944-8244
- Publication date
- 19.10.2016
- Publication status
- Published
- Peer reviewed
- Yes
- ASJC Scopus subject areas
- Materials Science(all)
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Electronic version(s)
-
https://doi.org/10.1021/acsami.6b09204 (Access:
Closed)
