We reported SN38-loaded polymersomes formulated with amphiphilic block copolymers based on HPMA and either ε-caprolactone or lactic acid through employing ring-opening polymerization, carbodiimide chemistry and a reversible addition-fragmentation chain transfer polymerization technique. In this regard, we successfully synthesized five chimeric polymersomes based on different percentage of the synthesized copolymers. The prepared chimeric polymersomes based on PCL-b-PHPMA:PLA-b-PHPMA at ratio of 1:3 exhibited superior loading capacity in comparison with other chimeric polymersomes. In order to increase therapeutic index of the prepared systems, AS1411 aptamer was implemented as targeting ligand. In vivo study revealed that the intravenous single dose injection of targeted chimeric polymersomes to C26 tumor bearing mice had remarkable efficacy in inhibiting tumor growth. It could be concluded that the chimeric polymersomes fabricated from PCL-b-PHPMA and PLA-b-PHPMA at a ratio of 1:3 have great potential for SN38 encapsulation while providing controlled sustained release properties with targeting capability via AS1411 aptamer conjugation.
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