Antitumor Cytokine DR5-B-Conjugated Polymeric Poly(N-vinylpyrrolidone) Nanoparticles with Enhanced Cytotoxicity in Human Colon Carcinoma 3D Cell Spheroids

Self-assembled nanoparticles based on amphiphilic poly(N-vinylpyrrolidone) (Amph-PVP) were proposed earlier as a new drug delivery system. In the current work, we study antitumor activity of Amph-PVP-based self-assembled polymeric micelles covalently conjugated with receptor-specific TRAIL variant DR5-B (P-DR5-B). The Amph-PVP polymer was synthesized by developed one-step technique (Kulikov et al., Polym. Sci. Ser. D, 2017). To stabilize associates, hydrophobic core loaded model substance prothionamide. For covalent conjugation DR5-B, hydrophilic ends chains modified maleimide, and N-terminal amino acid residue valine mutated to cysteine (DR5-B/V114C). DR5-B/V114C surface selective interaction maleimide Amph-PVP. cytotoxicity DR5-B-conjugated investigated in 3D multicellular tumor spheroids (MCTS) human colon carcinoma HCT116 HT29 cells, generated RGD-induced self-assembly (Akasov Int. J. Pharm., 2016). DR5-B-sensitive MCTS, P-DR5-B slightly increased compared that DR5-B. However, DR5-B-resistant significantly surpassed activity. Thus, enhanced its tumor-cell killing capacity. study, obtain nano-scaled system self-aggregates coated DR5-specific cytokine overcomes DR5-B-resistance MCTS vitro. This makes prospective versatile for targeted proteins.