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 (99mTc) 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.

Highlights

  • Technetium-99m ( 99mTc; half-life, 6.02 h; γ-energy, 140.5 KeV) is a commonly used nuclide in biodistribution, drug tracing and molecular imaging applications due to its low cost, excellent availability, little impact on drug biochemical properties, photon energy that is nearly ideal for single-photon emission computed tomography (SPECT) and low absorbed-dose burden to the patients.In this study, an amphiphilic polymer, namely peptides K237 (HTMYYHHYQHHL) and folic acid (FA) modified poly(ethylene glycol)poly(lactic-co-glycolic acid) (K237/FA-Polyethylene glycol (PEG)-PLGA), was www.impactjournals.com/oncotarget used to prepare nanoparticles (NPs) which can serve as favorable carriers for the delivery of certain drugs [1,2,3,4]

  • 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

  • K237/FA-PEG-PLGA nanoparticles were effectively labeled by a direct method with Technetium-99m (99mTc) using stannous chloride as a reducing agent

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Summary

INTRODUCTION

Technetium-99m ( 99mTc; half-life, 6.02 h; γ-energy, 140.5 KeV) is a commonly used nuclide in biodistribution, drug tracing and molecular imaging applications due to its low cost, excellent availability, little impact on drug biochemical properties, photon energy that is nearly ideal for single-photon emission computed tomography (SPECT) and low absorbed-dose burden to the patients. An amphiphilic polymer, namely peptides K237 (HTMYYHHYQHHL) (target the vascular endothelial growth factor receptor-2, abbreviation: VEGFR-2 or KDR) and folic acid (FA) modified poly(ethylene glycol)poly(lactic-co-glycolic acid) (K237/FA-PEG-PLGA), was www.impactjournals.com/oncotarget used to prepare nanoparticles (NPs) which can serve as favorable carriers for the delivery of certain drugs [1,2,3,4]. In this delivery system, the covalent conjugation of K237 and FA to the NPs confers them the ability to actively bind the KDR receptor and folate receptor (FR). We used the radioisotope 99mTc to label the delivery system and study the distribution of radioactivity in various tissues following administration of the labelled NPs by performing gamma imaging of the whole body at predetermined time point

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