An Integrative Folate-Based Metal Complex Nanotube as a Potent Antitumor Nanomedicine as Well as an Efficient Tumor-Targeted Drug Carrier

Abstract

Metal-organic complexes (MOCs) are emerging developing functional materials, the different categories of metal ions and organic biomolecules provide great possibilities for the morphologies, sizes, and properties of the products. Enlightened by the previous works of folate-nickel nanotubes (FA-Ni NTs), herein, a series of metal ions are tested to coordinate with folate (FA) by the solvothermal method, among which the folate-cobalt(II) complex is formed to be a scaffold for the nanotube with the length of 150-500 nm and inner diameter of 6-11 nm, while the other metal ions fail. In vitro experiments reveal that folate-cobalt nanotubes (FA-Co NTs) have excellent antitumor activity toward tumor cells with high expression levels of folate receptor (FR), whereas they show extremely low toxicity to normal cells. Furthermore, these kinds of NTs show better antitumor ability when the anticancer drug doxorubicin is encapsulated through cell surface receptor-mediated endocytosis. Moreover, we study the fundamental pharmacokinetic profiles and biodistribution of FA-Co NTs on mice and also prove its targeting capability to tumor tissues on tumor-bearing mice using the radioactive iodine-131 (I) tracing method. FA-Co NTs can also markedly inhibit the growth of tumor with minimal side effects when administered individually in vivo. These findings will expand the research on FA based metal complex nanomaterials as a kind of potential antitumor nanomedicine as well as a targeted drug carrier.

Radiolabeling strategies and pharmacokinetic studies for metal based nanotheranostics

“…A technique to minimize this problem is by employing nonmetallic radionuclides instead of metallic radionuclides (Ge et al, 2019). The most common nonmetallic radioisotopes which are covalently bound to MNPs through prosthetic groups are 11 C (R. Sharma et al, 2013), 14 C (Nallathamby et al, 2015), 18 F (S. Rojas et al, 2012), 123 I (Z. Zhang, 2016), 124 I (J. Lee et al, 2013), 125 I (Jang et al, 2012; S. Liu et al, 2009; Y. Tang et al, 2015), and 131 I (L. X. Liu et al, 2016).…”

Phenylboronic ester-modified anionic micelles for ROS-stimuli response in HeLa cell

“…We discovered that the weight of all five groups of mice did not change obviously at the end of treatment. (Figure 10) Meanwhile after treatment with PBS, PEG-b-PAsp-g-PBE, free DOX, PEG-b-PAsp/DOX and PEG-b-PAsp-g-PBE/DOX for 18 days, we sacrificed mice, collected all the tumor tissues and measured them respectively (Liu et al, 2016;Wang et al, 2019).…”

“…The tumor volume was figured out according to the following equation: volume ¼ tumor width 2 Âtumor length/2. In vivo experiments were conducted when the tumor average volume reached 120-150 mm 3 (Liu et al, 2016;Li et al, 2017;Wang et al, 2019).…”

Radiolabeled Nanoparticles in Nuclear Oncology

“…A variety of metal-organic complexes was investigated, focusing especially on Cobalt (Co) nanotubes (NTs) functionalized with folic acid. Doxorubicin was embedded in these targeted nanocarriers which were traceable in murine models with the aid of 131 I. Tumor growth was found to be suspended in vivo, with minimal side effects reported [84]. A self-assembled amphiphilic, protein-based conjugate comprised of hydrophobic maleimidefunctionalized poly-(ε-caprolactone) (PCL) covalently linked to hydrophilic bovine serum albumin (BSA), was directly labeled with 131 I.…”