Immune activity and biodistribution of polypeptide K237 and folic acid conjugated amphiphilic PEG-PLGA copolymer nanoparticles radiolabeled with 99mTc

// Zelai He 1, 3, * , Xiangyu Zhang 4, * , Jingwen Huang 1, 3, * , Yufeng Wu 5 , Xuanzhang Huang 1 , Jie Chen 1 , Junyong Xia 6 , Hao Jiang 3 , Jing Ma 2 , Jian Wu 1 1 The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China 2 Ultrasonic Department, Shanghai Songjiang Center Hospital, Shanghai, China 3 The First Affiliated Hospital of Bengbu Medical College, Bengbu, China 4 Department of Pathology, Jining No.1 Peoples’ Hospital, Jining, China 5 Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China 6 Department of Nuclear Medicine, The Affiliated Provincial Hospital of Anhui Medical University, Hefei, China * These authors contributed equally to this work Correspondence to: Junyong Xia, email: xiabingbing@126.com Hao Jiang, email: jianghao1223@163.com Jing Ma, email: majing0709@163.com Jian Wu, email: wzzjian@hotmail.com Keywords: K237, folate, PEG-PLGA, nanoparticles, biodistribution Received: July 29, 2016 Accepted: October 12, 2016 Published: October 24, 2016 ABSTRACT In a previous study, amphiphilic copolymer, polypeptide K237 (HTMYYHHYQHHL) and folic acid (FA) modified poly(ethylene glycol)-poly(lactic-co-glycolic acid) (K237/FA-PEG-PLGA) nanoparticles were developed and studied as a drug carrier. To further promote the clinical application of K237/FA-PEG-PLGA nanoparticles and provide guidance for future research, we need to examine their specific biodistribution in vivo . In this study, K237/FA-PEG-PLGA nanoparticles were effectively labeled by a direct method with Technetium-99m ( 99m Tc) using stannous chloride as a reducing agent. The optimal stability of the labeled nanoparticles was determined by evaluating their radiochemical purity in serum, physiological saline, diethylenetriaminepentaacetic acid (DTPA) and cysteine solutions. The affinity of ligands and receptors was elicited by cell binding and blocking experiments in KDR/folate receptor high expressing SKOV-3 ovarian cancer cells. The nanoparticles biodistribution was studied after intravenous administration in healthy mice xenografted with SKOV-3 cells. A higher percent injected dose per gram of tissue (% ID/g) was observed in liver, kidney, spleen, blood and tumor at 3 and 9 h post-injection. Scintigraphic images revealed that the radioactivity was mainly concentrated in tumor, liver, kidney and bladder; and in the heart, lung, and muscle was significantly lower at 3 h. The radioactivity distribution in the images is consistent with the in vivo biodistribution data. Our works demonstrated that K237/FA-PEG-PLGA nanoparticles have great potential as biodegradable drug carriers, especially for tumors expressing the folate and KDr receptor.