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The highly efficient delivery of exogenous proteins into cells mediated by biodegradable chimaeric polymersomes

Paper ID Volume ID Publish Year Pages File Format Full-Text
7865 567 2010 11 PDF Available
Title
The highly efficient delivery of exogenous proteins into cells mediated by biodegradable chimaeric polymersomes
Abstract

Biodegradable chimaeric polymersomes based on asymmetric PEG-PCL-PDEA triblock copolymers were prepared and investigated for delivery of exogenous proteins into cells. PEG-PCL-PDEA copolymers with MnPEG = 5 kg/mol, MnPCL = 18.2 kg/mol, and short PDEA blocks ranging from 1.1, 2.7 to 4.1 kg/mol (denoted as copolymer 1, 2 and 3, respectively) were obtained by controlled reversible addition-fragmentation chain transfer (RAFT) polymerization. The direct hydration of copolymer thin films in MES buffer (pH 5.3) yielded uniform polymersomes with sizes of 130–175 nm. These polymersomes had close to neutral zeta potentials (−2 ∼ +2.7 mV) at pH 7.4. The polymersomal structures were confirmed by confocal laser scanning microscopy (CLSM), transmission electron microscopy (TEM), and catalytic activity experiment on 3,3′,3″-phosphinidyne(trisbenzenesulfonic acid)-loaded polymersomes. MTT assays showed that these polymersomes were non-toxic up to a concentration of 0.5 mg/mL. These chimaeric polymersomes, in particular polymersome 2, showed remarkably high protein loading efficiencies and loading contents for bovine serum albumin (BSA), cytochrome C (CC), lysozyme (Lys), ovalbumin (OVA) and immunoglobulin G (IgG). The encapsulation of proteins did not significantly alter the polymersome size distributions and zeta potentials. The protein release studies showed that both BSA and CC were released in a controlled manner. Importantly, the released CC fully maintained its activity. Notably, CLSM studies showed that FITC-CC loaded polymersomes efficiently delivered and released proteins into the cytoplasm of RAW 264.7 cells. Moreover, these chimaeric polymersomes were able to simultaneously load and transport proteins and doxorubicin into the cytoplasm as well as the cell nucleus. We are convinced that these biodegradable chimaeric polymersomes have great potentials in protein therapy.

Keywords
Biodegradable; Polymersomes; Protein delivery; Drug delivery; Intracellular release; Cancer therapy
First Page Preview
The highly efficient delivery of exogenous proteins into cells mediated by biodegradable chimaeric polymersomes
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 31, Issue 29, October 2010, Pages 7575–7585
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering