Exosome-based strategy against colon cancer using small interfering RNA-loaded vesicles targeting soluble a proliferation-inducing ligand.

Abstract

Recent advancements in nanomedicine have highlighted the potential of exosome (Ex)-based therapies, utilizing naturally derived nanoparticles, as a novel approach to targeted cancer treatment. To explore the targetability and anticancer effectiveness of small interfering peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 RNA (siPIN1)-loaded soluble a proliferation-inducing ligand (sAPRIL)-targeted Exs (designated as tEx[p]) in the treatment of colon cancer models. tEx was generated by harvesting conditioned media from adipose-derived stem cells that had undergone transformation using pDisplay vectors encoding sAPRIL-binding peptide sequences. Subsequently, tEx[p] were created by incorporating PIN1 siRNA into the tEx using the Exofect kit. The therapeutic efficacy of these Exs was evaluated using both in vitro and in vivo models of colon cancer. The tEx[p] group exhibited superior anticancer effects in comparison to other groups, including tEx, Ex[p], and Ex, demonstrated by the smallest tumor size, the slowest tumor growth rate, and the lightest weight of the excised tumors observed in the tEx[p] group (P < 0.05). Moreover, analyses of the excised tumor tissues, using western blot analysis and immunohistochemical staining, revealed that tEx[p] treatment resulted in the highest increase in E-cadherin expression and the most significant reduction in the mesenchymal markers Vimentin and Snail (P < 0.05), suggesting a more effective inhibition of epithelial-mesenchymal transition tEx[p], likely due to the enhanced delivery of siPIN1. The use of bioengineered Exs targeting sAPRIL and containing siPIN1 demonstrated superior efficacy in inhibiting tumor growth and epithelial-mesenchymal transition, highlighting their potential as a therapeutic strategy for colon cancer.