Efficient delivery of anlotinib and radioiodine by long circulating nano-capsules for active enhanced suppression of anaplastic thyroid carcinoma

131I therapy is clinically unfeasible for anaplastic thyroid carcinoma (ATC), due to lack of active targets and ATC's resistance to radiation. Novel radionuclide-labeled targeted nano-drug delivery systems have exhibited the potential of prominent tumor imaging and remedy. Capitalizing on recent research achievements in nanotechnology and nuclear medicine, we sought to develop a radiolabeled nano-drug, which could specifically accumulate in ATCs via tumor-selective targeted delivery system and which could treat the tumors with both targeted and radionuclide therapeutics. Epidermal growth factor receptor (EGFR) and mutant P53 expressions were positive in 80% and 60% of patients with ATC, respectively. Herein, core-shell nanoparticles-based poly (ethyleneglycol)-crosslinker (PEG-CL) was fabricated, by encapsulating bovine serum albumin (BSA) inside the core and an enzyme with various tyrosine residues for 131I radiolabeling, and by loading anlotinib, a multi-kinase inhibitor which can site-selectively target overexpressed EGFR in ATC cells and which also suppresses angiogenesis, onto the PEG-CL shell surface. The Anlotinib-BSA nano-capsule (nBSA) showed a mostly uniform size distribution centering at 21-23 nm, and the nano-drug had a characteristic absorption peak at the wavelength of 325 nm. The Anlotinib-nBSA had a high labeling efficiency with the radiochemical purity being approximately 100%. The cellular uptake efficiency of Anlotinib-nBSA-131I was much higher than that of free 131I in both 8305C (3.6% vs 0.0%) and C643 (7.0% vs 0.1%; with a higher EGFR expression level) ATC cell lines. Anlotinib-nBSA-131I showed the strongest cytotoxicity against ATC cells with different concentrations of anlotinib, and induced the highest rate of apoptosis (C643 cells, 81.7%). The nanoparticles could actively target tumor surface with anlotinib exhibiting enhanced radio-sensitization effects by functionally upregulating P53 and Bax. In vivo SPECT/CT imaging showed that the concentration of Anlotinib-nBSA-125I in tumors peaked at 24 h, and the intense signal persisted for at least one week. Anlotinib-nBSA-131I showed the strongest tumor inhibition effects in tumor-bearing mice, with no evident pathological changes observed. Together, the optimal nanoparticles co-loading anlotinib and 131I satisfactorily demonstrated efficient drug delivery and prominent antitumor effects both in vitro and in vivo, without obvious in vivo bio-toxicity. Our innovation could offer novel effective strategies for targeted management of ATC, a highly-aggressive disease with dismal prognosis.