Tumor Targeted Delivery of an Anti‐Cancer Therapeutic: An In Vitro and In Vivo Evaluation. Issue 2 (16th November 2020)

• Record Type: Journal Article
• Authors: Kang, You Jung; Holley, Claire K.; Abidian, Mohammad Reza; Madhankumar, Achuthamangalam B.; Connor, James; Majd, Sheereen
• Is Part Of: Advanced healthcare materials. Volume 10:Issue 2(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-11-16
• Subjects: delivery to glioma -- Dp44mT chelator -- in vitro studies -- in vivo studies -- interleukin 13 -- targeted nanoparticles; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/adhm.202001261
• Languages: English
• ISSNs: 2192-2640

Abstract

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. Abstract : This study presents a promising targeted nanoformulation based on a potent anti‐cancer chelator, Dp44mT, for the treatment of glioma tumors. IL13‐conjugated polymeric NPs loaded with Dp44mT show high level of cytotoxicity in glioma cell lines and glioma stem cells. In xenograft mouse models, these NPs significantly reduce the growth of glioma tumors without causing liver or kidney toxicity.