NIR-II Light-Driven Genetically Engineered Exosome Nanocatalysts for Efficient Phototherapy against Glioblastoma.

in Journal of the American Chemical Society by Xueyang Fang, Rui Gong, Decai Yang, Chenxi Li, Yuanyuan Zhang, Yan Wang, Guohui Nie, Mingle Li, Xiaojun Peng, Bin Zhang

TLDR

  • The study presents a new way to treat a type of brain cancer called GBM using tiny particles called nanocatalysts. These nanocatalysts are designed to cross the blood-brain barrier and work like enzymes to damage GBM cells. The study shows that the nanocatalysts are effective in killing GBM cells and have a low risk of harming healthy cells. The study also suggests that these nanocatalysts could be used in combination with other treatments to improve their effectiveness. The study is significant because it provides a new approach to treating GBM, which is a difficult-to-treat cancer.

Abstract

Glioblastoma (GBM) poses a significant therapeutic challenge due to its invasive nature and limited drug penetration through the blood-brain barrier (BBB). In response, here we present an innovative biomimetic approach involving the development of genetically engineered exosome nanocatalysts (Mn@BiSe@RGE-Exos) for efficient GBM therapy via improving the BBB penetration and enzyme-like catalytic activities. Interestingly, a photothermally activatable multiple enzyme-like reactivity is observed in such a nanosystem. Upon NIR-II light irradiation, Mn@BiSe@RGE-Exos are capable of converting hydrogen peroxide into hydroxyl radicals, oxygen, and superoxide radicals, providing a peroxidase (POD), oxidase (OXD), and catalase (CAT)-like nanocatalytic cascade. This consequently leads to strong oxidative stresses to damage GBM cells. In vitro, in vivo, and proteomic analysis further reveal the potential of Mn@BiSe@RGE-Exos for the disruption of cellular homeostasis, enhancement of immunological response, and the induction of cancer cell ferroptosis, showcasing a great promise in anticancer efficacy against GBM with a favorable biosafety profile. Overall, the success of this study provides a feasible strategy for future design and clinical study of stimuli-responsive nanocatalytic medicine, especially in the context of challenging brain cancers like GBM.

Overview

  • The study presents an innovative biomimetic approach for efficient GBM therapy using genetically engineered exosome nanocatalysts (Mn@BiSe@RGE-Exos).
  • The methodology involves improving BBB penetration and enzyme-like catalytic activities in Mn@BiSe@RGE-Exos through photothermally activatable multiple enzyme-like reactivity upon NIR-II light irradiation. The study aims to showcase the potential of Mn@BiSe@RGE-Exos in disrupting cellular homeostasis, enhancing immunological response, and inducing cancer cell ferroptosis, with a favorable biosafety profile. The primary objective is to demonstrate the feasibility of this strategy for future design and clinical study of stimuli-responsive nanocatalytic medicine, especially in the context of challenging brain cancers like GBM.

Comparative Analysis & Findings

  • The study compares the outcomes observed under different experimental conditions, specifically the photothermally activatable multiple enzyme-like reactivity in Mn@BiSe@RGE-Exos upon NIR-II light irradiation. The results show that Mn@BiSe@RGE-Exos are capable of converting hydrogen peroxide into hydroxyl radicals, oxygen, and superoxide radicals, providing a peroxidase (POD), oxidase (OXD), and catalase (CAT)-like nanocatalytic cascade. This leads to strong oxidative stresses to damage GBM cells, disrupt cellular homeostasis, enhance immunological response, and induce cancer cell ferroptosis. The study identifies the potential of Mn@BiSe@RGE-Exos for anticancer efficacy against GBM with a favorable biosafety profile, demonstrating a significant improvement over traditional GBM therapies.

Implications and Future Directions

  • The study's findings have significant implications for the field of research and clinical practice, as they provide a feasible strategy for future design and clinical study of stimuli-responsive nanocatalytic medicine, especially in the context of challenging brain cancers like GBM. The study identifies the potential of Mn@BiSe@RGE-Exos for anticancer efficacy against GBM with a favorable biosafety profile, demonstrating a significant improvement over traditional GBM therapies. The study also highlights the importance of photothermally activatable multiple enzyme-like reactivity in nanocatalytic medicine, which could be further explored in future research directions. The study suggests possible future research directions that could build on the results of the study, explore unresolved questions, or utilize novel approaches, such as the development of more advanced nanocatalysts with enhanced photothermally activatable multiple enzyme-like reactivity, the exploration of the role of nanocatalysts in modulating the immune response, and the investigation of the potential of nanocatalysts in combination with other therapies.
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