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 (¹³¹I), in a single platform.
Methods: The obtained nanoparticles (Cetuximab [Cet]-PEG-PLA-5Fu-¹³¹I) 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-¹³¹I 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-¹³¹I 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-¹³¹I. In the xenograft mouse model, compared with using Cet-PEG-PLA-5Fu or Cet-PEG-PLA-¹³¹I alone, Cet-PEG-PLA-5Fu-¹³¹I 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-¹³¹I nanoparticles was associated with smaller tumor sizes than monotherapy, revealing the superior antitumor effects of Cet-PEG-PLA-5Fu-¹³¹I nanoparticles. These effects were further evidenced by histological and immunohistochemical analyses.
Conclusion: The multifunctional Cet-PEG-PLA-5Fu-¹³¹I nanoparticles are promising candidates for the co-delivery of 5Fu-mediated chemotherapy and ¹³¹I-mediated radiotherapy.
Keywords: PEG-PLA, 5Fu, ¹³¹I, drug delivery, radio-chemotherapy, colorectal cancer