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 M(n)(PEG) = 5 kg/mol, M(n)(PCL) = 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 approximately +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 0.5mg/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.
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