Mesenchymal Stem Cell-Mediated Deep Tumor Delivery of Gold Nanorod for Photothermal Therapy

Wan Su Yun, Man Kyu Shim, Seungho Lim, Sukyung Song, Jinseong Kim, Suah Yang, Hee Sook Hwang, Mi Ra Kim, Hong Yeol Yoon, Dong-Kwon Lim, In Cheol Sun, Kwangmeyung Kim

Research output: Contribution to journalArticlepeer-review

Abstract

Gold nanoparticles (AuNPs) with various sizes and morphologies have been extensively investigated for effective photothermal therapy (PTT) against multiple cancer types. However, a highly dynamic and complex tumor microenvironment (TME) considerably reduces the efficacy of PTT by limiting deep tumor penetration of AuNPs. Herein, we propose a mesenchymal stem cell (MSC)-mediated deep tumor delivery of gold nanorod (AuNR) for a potent PTT. First, MSCs are treated with tetraacylated N-azidomannosamine (Ac4ManNAz) to introduce modifiable azide (N3) groups on the cell surface via metabolic glycoengineering. Then, AuNRs modified with bio-orthogonal click molecules of bicyclo[6.1.0]nonyne (AuNR@BCN) are chemically conjugated to the N3 groups on the MSC surface by copper-free click chemistry reaction, resulting in AuNR@MSCs. In cultured MSCs, the appropriate condition to incorporate the AuNR into the MSCs is optimized; in addition, the photothermal efficiency of AuNR-MSCs under light irradiation are assessed, showing efficient heat generation in vitro. In colon tumor-bearing mice, intravenously injected AuNR@MSCs efficiently accumulate within the tumor tissues by allowing deep tissue penetration owing to the tumor homing effect by natural tumor tropism of AuNR@MSCs. Upon localized light irradiation, the AuNR@MSCs significantly inhibit colon tumor growth by the enhanced photothermal effect compared to conventional AuNRs. Collectively, this study shows a promising approach of MSCs-mediated deep tumor delivery of AuNR for effective PTT.

Original languageEnglish
Article number3410
JournalNanomaterials
Volume12
Issue number19
DOIs
Publication statusPublished - 2022 Oct

Keywords

  • deep tumor penetration
  • drug delivery
  • gold nanorod
  • mesenchymal stem cell
  • photothermal therapy

ASJC Scopus subject areas

  • Chemical Engineering(all)
  • Materials Science(all)

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