Combined Therapeutic Effects of (131)I-Labeled and 5Fu-Loaded Multifunctional Nanoparticles in Colorectal Cancer

BACKGROUND: Owing to its combined effects, the co-delivery of different therapeutics is a promising option for the treatment of cancer. In the present study, tumor-targeting poly(ethylene glycol)-poly(lactic acid) (PEG-PLA) nanoparticles were developed for the transportation of two molecules, namely chemotherapeutic drug 5-fluorouracil (5Fu) and radionuclide iodine-131 ((131)I), in a single platform. METHODS: The obtained nanoparticles (Cetuximab [Cet]-PEG-PLA-5Fu-(131)I) were spherical (diameter approximately 110 nm) and pH-sensitive. The targeting effect of nanoparticles via Cet was confirmed in colorectal cancer cells using a fluorescent assay. The combined effects of Cet-PEG-PLA-5Fu-(131)I on cell viability and apoptosis were evaluated in colorectal cancer cells by Cell Counting Kit-8 and flow cytometry assays. RESULTS: Blank nanoparticles (Cet-PEG-PLA) showed good biocompatibility, and Cet-PEG-PLA-5Fu-(131)I nanoparticles were the most effective in terms of inhibition of cell viability and induction of apoptosis compared with monotherapy using Cet-PEG-PLA-5Fu or Cet-PEG-PLA-(131)I. In the xenograft mouse model, compared with using Cet-PEG-PLA-5Fu or Cet-PEG-PLA-(131)I alone, Cet-PEG-PLA-5Fu-(131)I nanoparticles exhibited prolonged circulation in the blood and accumulation in the tumor, thus resulting in enhanced antitumor efficacy. Additionally, combined radio-chemotherapy with Cet-PEG-PLA-5Fu-(131)I nanoparticles was associated with smaller tumor sizes than monotherapy, revealing the superior antitumor effects of Cet-PEG-PLA-5Fu-(131)I nanoparticles. These effects were further evidenced by histological and immunohistochemical analyses. CONCLUSION: The multifunctional Cet-PEG-PLA-5Fu-(131)I nanoparticles are promising candidates for the co-delivery of 5Fu-mediated chemotherapy and (131)I-mediated radiotherapy.