Tetrac-conjugated polymersomes for integrin-targeted delivery of camptothecin to colon adenocarcinoma in vitro and in vivo

In this study, we prepared tetraiodothyroacetic acid (tetrac) conjugated PEG-PLGA polymersomes for the targeted delivery of camptothecin to colon adenocarcinoma. Tetrac, which binds to integrin alpha(v)beta(3) with high affinity and specificity, was covalently conjugated to the surface of the PEGylated polymersomal formulation of camptothecin (CPT). The hydrodynamic and morphological properties of the prepared system were evaluated using TEM (transmission electron microscopy), SEM (scanning electron microscopy) and DLS (dynamic light scattering) experiments. Camptothecin was encapsulated in the polymersomal system with encapsulation efficiency and loading content of 84 +/- 10.12 and 4.2 +/- 0.82, respectively. The in vitro release profile of camptothecin from the polymersomal formulation revealed the sustained release pattern. In vitro cytotoxicity experiments confirmed that the tetrac-conjugated camptothecin loaded-polymersomes had higher cellular toxicity towards integrin-overexpressed HT29 and C26 colorectal cancer cells than integrin-negative CHO cell line. The in vivo tumor inhibitory effect of tetrac-conjugated camptothecin loaded-polymersomes demonstrated an enhanced therapeutic index of integrin targeted polymersomal formulation over both non-targeted polymersomal formulation and free camptothecin in C26 tumor bearing mice. The obtained results demonstrated that the prepared tetrac-conjugated polymersomes were able to control the release of camptothecin, and significantly increase the therapeutic index of compthotecin. This study demonstrates the versatility of integrin-targeted tetrac-conjugated PEG-PLGA polymersomal formulation as an anti-cancer nano-pharmaceutical platform.