Cetuximab–Radionuclide Functionalized Polymeric Nanocomplexes: A Radiopharmaceutical Perspective for Liver Cancer

Liver cancer is a highly vascularized and one of the most drug resistant forms of solid tumors. Therapeutic options for liver cancer treatment are very limited and the prognosis is poor. Patients get diagnosed at a late stage of liver cancer. Many conventional chemotherapeutics are non-selective for liver cancer cells. An urgent need exists to develop improved methods of tumor-specific targeting.

Polymeric PLGA nanocomplexes was synthesized and developed at the Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay in Mumbai, India. We were eager and excited to look at the radiopharmaceutical perspective.

Research team demonstrated cetuximab–radionuclide functionalized polymeric nanocomplexes provided the means to deliver drugs at a prolonged rate to specific cancer targets. 

Biodistribution studies of 125I-Cet-PLGA-b-PEG NP was monitored in tumor, blood, liver, lung, kidney, spleen, urinary bladder, bone, muscle, heart, thyroid at 3 hours, 24 hours, and 48 hours post-intravenous injection in a liver cancer SCID mice model. Tracer uptake was observed time dependent in different organs. Cetuximab targeted 125I radionuclide radiolabeled polymeric nanoparticles viz; 125I–Cet-PLGA-b-PEG NP showed potent accumulation and retention in liver tumors with longer circulation time up to 48 hours.1

Pegylation of nanocomplexes lead to sustained blood circulation. Such longer tumor retention capability is indicative of maximum therapeutic efficacy and few side effects. It also signifies its uptake through EGFR receptor-mediated internalization process in tumor cells with high affinity. On yet another note, 18F-FDG PET analysis demonstrated that combinatorial targeted polymeric nanocomplexes strongly reduced the tumor growth and metabolic activity in liver cancer mice models.2

The radionuclide study was conducted in collaboration with Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Navi Mumbai, and Board of Radiation and Isotope Technology (BRIT), Navi Mumbai, India.

A way forward- This modality could serve for radio-immunotheranostics application platform against liver cancer.

References

1. Poojari Radhika, Mohanty B, Kadwad V, et al. Combinatorial cetuximab targeted polymeric nanocomplexes reduce PRC1 level and abrogate growth of metastatic hepatocellular carcinoma in vivo with efficient radionuclide uptake. Nanomedicine. Published online January 30, 2022. doi:10.1016/j.nano.2022.102529
2. Poojari R, Mohanty B, Kadwad V, et al. A comprehensive analysis of Cetuximab combinatorial polymeric nanocomplexes with potent radionuclide uptake to combat metastatic liver cancer. Eur J Cancer 2020;138(suppl 2; S38). doi:10.1016/S0959-8049(20)31173-4

Editor’s Note: Radhika Poojari, PhD, is lead author of the study being conducted at IIT Bombay in Mumbai, India.