Prominin-1-Specific Binding Peptide-Modified Apoferritin Nanoparticle Carrying Irinotecan as a Novel Radiosensitizer for Colorectal Cancer Stem-Like Cells

Abstract

Resistance of cancer stem cells to radiotherapy remains a major obstacle to successful cancer management. Prominin-1 (PROM1) is a cancer stem cell marker. Nanoparticle (NP) chemotherapeutics preferentially accumulate in tumors and are able to target cancer and cancer stem-like cells through cancer cell-specific ligands, making them uniquely suited as radiosensitizers for chemoradiation therapy. Using a biocompatible apoferritin NP, a PROM1-targeted NP carrying irinotecan (PROM1-NP) is engineered. The synergistic effect of the NP and irradiation is evaluated in PROM1-overexpressing HCT-116 colorectal cancer cell lines in vitro and in vivo. PROM1-NP has a size of 17.2 ± 0.2 nm and surface charge of −13.5 ± 0.2 mV. It demonstrates higher intracellular uptake than nontargeted NP or irinotecan alone. Treatment with PROM1-NPs decreases HCT-116 cell proliferation in a dose- and time-dependent manner. In vitro radiosensitization reveals that PROM1-NP is significantly more effective as a radiosensitizer than nontargeted NP or irinotecan. HCT-116 tumor xenograft growth is markedly slower following treatment with PROM1-NP plus irradiation, suggesting that PROM1-NP is more effective as a radiosensitizer than irinotecan and nontargeted NP in vivo. This study provides the first preclinical evidence of the effectiveness of PROM1-targeted NP formulation of irinotecan as a radiosensitizer.