Tumor Targeted Delivery of an Anti-Cancer Therapeutic: An In Vitro and In Vivo Evaluation

You Jung Kang, Claire K. Holley, Mohammad Reza Abidian, Achuthamangalam B. Madhankumar, James Connor, Sheereen Majd

Research output: Contribution to journalArticlepeer-review

Abstract

The limited effectiveness of current therapeutics against malignant brain gliomas has led to an urgent need for development of new formulations against these tumors. Chelator Dp44mT (di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone) presents a promising candidate to defeat gliomas due to its exceptional anti-tumor activity and its unique ability to overcome multidrug resistance. The goal of this study is to develop a targeted nano-carrier for Dp44mT delivery to glioma tumors and to assess its therapeutic efficacy in vitro and in vivo. Dp44mT is loaded into poly(ethylene glycol) (PEG)ylated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) decorated with glioma-targeting ligand Interlukin 13 (IL13). IL13-conjugation enhanced the NP uptake by glioma cells and also improved their transport across an in vitro blood-brain-barrier (BBB) model. This targeted formulation showed an outstanding toxicity towards glioma cell lines and patient-derived stem cells in vitro, with IC50 values less than 125 nM, and caused no significant death in healthy brain microvascular endothelial cells. In vivo, when tested on a xenograft mouse model, IL13-conjugated Dp44mT-NPs reduced the glioma tumor growth by ≈62% while their untargeted counterparts reduced the tumor growth by only ≈16%. Notably, this formulation does not cause any significant weight loss or kidney/liver toxicity in mice, demonstrating its great therapeutic potential.

Original languageEnglish (US)
Article number2001261
JournalAdvanced Healthcare Materials
Volume10
Issue number2
DOIs
StatePublished - Jan 20 2021

All Science Journal Classification (ASJC) codes

  • Biomaterials
  • Biomedical Engineering
  • Pharmaceutical Science

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