Abstract
In this study, synthesis of Polylactic acid (PLA) polymer was carried out through ring-opening polymerization (ROP) method. Then, 4-cyano-4-(phenylcarbonothioylthio)pentanoic acid as the CTA molecule was attached to the PLA, and subsequently, amphiphilic copolymer, with estimated structure of Poly(lactic acid)121-b-Poly(N-(3-aminopropyl)methacrylamide)103 (PLA121-b-PAPMA103) was obtained through the Reversible Addition Fragmentation chain Transfer (RAFT) reaction. The synthesized copolymer was self-assembled into spherical nanoparticles with size, Poly Dispersity Index (PDI) and zeta potential of 181.5 ± 21.3, 0.643 and of 44.9 ± 2.5 mV, respectively. The optimal copolymer/plasmid ratio was 4 with size, PDI and zeta potential of 161.7 ± 10.2, 0.277 and 36.5 ± 0.7, respectively for the delivery of short hairpin RNA (shRNA) plasmid against survivin. Additionally, the AS1411 aptamer was electrostatically decorated on the surface of the polyplex. In vitro studies on C26 cells revealed that the aptamer rendered nanoparticle transfer into the cell, dependent solely on the aptamer-receptor interactions. Lastly, in vivo studies involving tumor size and body weight change, survival and histological analysis indicated potential therapeutic index of the targeted nanoparticles with good safety profile.
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