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 doseand 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.

Panitumumab-Conjugated and Platinum-Cored pH-Sensitive Apoferritin Nanocages for Colorectal Cancer-Targeted Therapy

“…Many promising nanoparticles have been developed, such as liposomes, micelles, and carbon nanotubes. , However, biocompatibility and metabolism issues related to these nanoparticles have limited their clinical applications. , Recently, protein nanomedicines, such as abraxane (protein-bound paclitaxel), have been used in the treatment of breast and pancreatic cancers and have received much attention . Protein-based nanoparticles have demonstrated significant advantages over other synthetic nanoparticles because of their stability, small size, high biocompatibility, biodegradability, low cytotoxicity, and high surface area that contains many amino functional groups that can easily be modified, such as conjugated antibodies or peptide ligands. − …”

Targeting cancer stem cells with polymer nanoparticles for gastrointestinal cancer treatment

“…and Zhang et al . also achieved selective targeting of CSCs through specific ligand-conjugated nanoparticles [ 85 , 86 ]. From the above studies, we can find that the coupling of ligands can significantly improve the targeting of nanoparticles to colorectal CSCs.…”

Near-Infrared Fluorescent Dye-Decorated Nanocages to Form Grenade-like Nanoparticles with Dual Control Release for Photothermal Theranostics and Chemotherapy

“…Carrier molecules are needed to overcome the hydrophobic properties of photosensitizer drugs to achieve efficient targeting. Typically, polymeric micelles, silica-based NPs, nanotubes, and nanogold are utilized as artificial carrier molecules. − However, the use of such artificial carrier molecules mostly may impose an immune response on the patient; manufacturing process complexity and critical problems related to their biocompatibility have largely impeded the related developments. − Compared with conventional carrier molecules, the application of protein NPs for drug delivery has continued to attract increasing attention over the past few years. , In fact, several protein cages composed of albumin, ferritin, transferrin, small heat shock proteins, and virus-like particles have been developed. − Especially, Abraxane (an albumin-bound formulation of paclitaxel) was approved by the FDA as a solvent-free formulation of paclitaxel for the treatment of metastatic breast cancer. , The hydrophobic drug becomes soluble once bound to albumin. In this study, apoferritin nanocages (AF NCs), which have a biologically appropriate inner diameter of 8 nm and outer diameter of 12 nm, were employed as ideal NPs for drug delivery.…”