Engineered Microparticles for Treatment of Murine Brain Metastasis by Reprograming Tumor Microenvironment and Inhibiting MAPK Pathway

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

12 Scopus Citations
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Author(s)

  • Lisen Lu
  • Huaduan Zi
  • Jie Zhou
  • Jing Huang
  • Zihan Deng
  • Zijian Tang
  • Li Li
  • Xiujuan Shi
  • Jonathan F. Lovell
  • Deqiang Deng
  • Chao Wan
  • Honglin Jin

Related Research Unit(s)

Detail(s)

Original languageEnglish
Article number2206212
Journal / PublicationAdvanced Science
Volume10
Issue number8
Online published25 Jan 2023
Publication statusPublished - 15 Mar 2023

Link(s)

Abstract

Brain metastases (BRM) are common in advanced lung cancer. However, their treatment is challenging due to the blood-brain barrier (BBB) and the immunosuppressive tumor microenvironment (ITME). Microparticles (MPs), a type of extracellular vesicle, can serve as biocompatible drug delivery vehicles that can be further modulated with genetic engineering techniques. MPs prepared from cells induced with different insults are compared and it is found that radiation-treated cell-released microparticles (RMPs) achieve optimal targeting and macrophage activation. The enzyme ubiquitin-specific protease 7 (USP7), which simultaneously regulates tumor growth and reprograms M2 macrophages (M2𝚽), is found to be expressed in BRM. Engineered RMPs are then constructed that comprise: 1) the RMP carrier that targets and reprograms M2𝚽; 2) a genetically expressed SR-B1-targeting peptide for improved BBB permeability; and 3) a USP7 inhibitor to kill tumor cells and reprogram M2𝚽. These RMPs successfully cross the BBB and target M2𝚽 in vitro and in vivo in mice, effectively reprogramming M2𝚽 and improving survival in a murine BRM model. Therapeutic effects are further augmented when combined with immune checkpoint blockade. This study provides proof-of-concept for the use of genetically engineered MPs for the treatment of BRM. © 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.

Research Area(s)

  • blood-brain barrier, cancer immunotherapy, extracellular vesicles, macrophages polarization, USP7, MACROPHAGES, CELLS, IMMUNOTHERAPY, RADIATION, EXOSOMES, ANTIGENS

Citation Format(s)

Engineered Microparticles for Treatment of Murine Brain Metastasis by Reprograming Tumor Microenvironment and Inhibiting MAPK Pathway. / Lu, Lisen; Zi, Huaduan; Zhou, Jie et al.
In: Advanced Science, Vol. 10, No. 8, 2206212, 15.03.2023.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

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