Folate Decorated Multifunctional Biodegradable Nanoparticles for Gastric Carcinoma Active Targeting Theranostics

Xin Zhang,1,* Ronglin Yan,1,* Ziran Wei,1,* Dejun Yang,1 Zunqi Hu,1 Yu Zhang,1 Xin Huang,1 Hejing Huang,2 Weijun Wang1 1Department of Gastrointestinal Surgery, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, People’s Republic of China; 2Department of Ultrasound, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hejing Huang, Tel +86-21-81886051, Email huanghejinga@163.com; Weijun Wang, Tel +86-21-81885602, Email wangweijun@smmu.edu.cnIntroduction: Gastric cancer remains a major clinical issue and little progress has been made in the treatment of gastric cancer patients during recent decades. Nanoparticles provide a versatile platform for the diagnosis and treatment of gastric cancer.Methods: We prepared 7-ethyl-10-hydroxycamptothecin (SN-38) 125I-radiolabelled biodegradable nanoparticles with folate surface modification (125I-SN-38-FA-NPs) as a novel nanoplatform for targeted gastric carcinoma theranostics. We characterized this system in terms of particle size, morphology, radiostability, and release properties and examined the in vitro cytotoxicity and cellular uptake properties of 125I-SN-38-FA-NPs in MNK 7 and NCI-N7 cells. The pharmacokinetics and biodistribution of 125I-SN-38-FA-NPs were imaged by single photon emission computer tomography (SPECT). An MNK7 tumor-bearing model were established and the in vivo antitumor activity of 125I-SN-38-FA-NPs was evaluated.Results: SN-38 was readily radiolabeled with 125I and exhibited high radiostability. Poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) were formed by solvent exchange, and displayed spherical morphology of 100 nm in diameter as characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). A 2.5-fold greater uptake of 125I-radiolabelled SN-38-loaded folate-decorated PLGA nanoparticles (125I-SN-38-FA-NPs) than 125I-radiolabelled SN-38-loaded PLGA nanoparticles (125I-SN-38-NPs) were record in MKN7 tumor cells. NPs and folate-decorated PLGA nanoparticles (FA-NPs) also had good biocompatibility in methyl thiazolyl tetrazolium (MTT) assays. Pharmacokinetic, biodistribution and SPECT imaging studies showed that 125I-SN-38-FA-NPs had prolonged circulation, were distributed in the reticuloendothelial system, and had high uptake in tumors with a higher tumor accumulation of 125I-SN-38-FA-NPs than 125I-SN-38-NPs recorded at 24 h postinjection. In vivo SN-38-FA-NPs significantly inhibited tumor growth without causing obvious side effects.Conclusion: Folate receptor alpha (FOLR1) targeted drug-loaded nanoparticles enable SPECT imaging and chemotherapy, and provide a novel nanoplatform for gastric carcinoma active targeting theranostics.Keywords: folate, biodegradable nanoparticles, active targeting, SN-38, SPECT