Journal Article

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

Zhang, Linlin, Zhu, Chuanying, Huang, Shuo, Huang, Lei, Wang, Hui, Liang, Sheng, Xu, Miaomiao, Cui, Zhilei, Li, Chao, Fu, Hongliang, Yin, Yafu

2025

Overview

131 I 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 131 I 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- 131 I was much higher than that of free 131 I 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- 131 I 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- 125 I in tumors peaked at 24 h, and the intense signal persisted for at least one week. Anlotinib-nBSA- 131 I showed the strongest tumor inhibition effects in tumor-bearing mice, with no evident pathological changes observed. Together, the optimal nanoparticles co-loading anlotinib and 131 I 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. Graphical Abstract

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Anaplastic thyroid carcinoma (ATC) / Angiogenesis / Animals / Anlotinib- and 131I-delivering nanoparticles / Antineoplastic Agents - chemistry / Antineoplastic Agents - pharmacology / Antitumor activity / Apoptosis / Biocompatibility / Biotechnology / Bovine serum albumin / Cancer therapies / Cell growth / Cell Line, Tumor / Chemistry / Chemistry and Materials Science / Chromatography / Computed tomography / Core-shell particles / Cytotoxicity / Drug delivery / Drug Delivery Systems / Efficacy / Epidermal growth factor / Epidermal growth factor receptors / ErbB Receptors - metabolism / Female / Genes / Growth factors / Humans / Indoles - administration & dosage / Indoles - chemistry / Indoles - pharmacokinetics / Indoles - pharmacology / Iodine / Iodine 131 / Iodine isotopes / Iodine radioisotopes / Iodine Radioisotopes - chemistry / Iodine Radioisotopes - pharmacokinetics / Iodine Radioisotopes - pharmacology / Kinases / Labeling / Medical imaging / Metastasis / Mice / Mice, Inbred BALB C / Mice, Nude / Molecular Medicine / Mutation / Nanoparticles / Nanoparticles - chemistry / Nanotechnology / Nuclear medicine / p53 Protein / Polyethylene Glycols - chemistry / Proteins / Quinolines - administration & dosage / Quinolines - chemistry / Quinolines - pharmacokinetics / Quinolines - pharmacology / Radiation therapy / Radiation tolerance / Radiochemistry / Radioisotopes / Radiolabelling / Safety / Serum albumin / Serum Albumin, Bovine - chemistry / Single photon emission computed tomography / Size distribution / Targeted nano-drug delivery / Thyroid / Thyroid cancer / Thyroid carcinoma / Thyroid Carcinoma, Anaplastic - drug therapy / Thyroid Carcinoma, Anaplastic - pathology / Thyroid Neoplasms - drug therapy / Tissue Distribution / Toxicity / Tumors / Tyrosine / Vascular endothelial growth factor