Engineered biomimetic nanoparticles achieve targeted delivery and efficient metabolism-based synergistic therapy against glioblastoma

Guihong Lu; Xiaojun Wang; Feng Li; Shuang Wang; Jiawei Zhao; Jinyi Wang; Jing Liu; Chengliang Lyu; Peng Ye; Hui Tan; Weiping Li; Guanghui Ma; Wei Wei

doi:10.1038/s41467-022-31799-y

Engineered biomimetic nanoparticles achieve targeted delivery and efficient metabolism-based synergistic therapy against glioblastoma

Nat Commun. 2022 Jul 21;13(1):4214. doi: 10.1038/s41467-022-31799-y.

Authors

Guihong Lu^{1

2}, Xiaojun Wang², Feng Li^{2

3}, Shuang Wang², Jiawei Zhao², Jinyi Wang¹, Jing Liu¹, Chengliang Lyu², Peng Ye², Hui Tan^{4

5}, Weiping Li⁶, Guanghui Ma^{7

8}, Wei Wei^{9

10}

Affiliations

¹ Department of Neurosurgery, Health Science Center, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, 518035, P. R. China.
² State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, P. R. China.
³ School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing, 100049, P. R. China.
⁴ Department of Neurosurgery, Health Science Center, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, 518035, P. R. China. huitan@email.szu.edu.cn.
⁵ Pneumology Department, Shenzhen Children's Hospital, Shenzhen, 518026, P. R. China. huitan@email.szu.edu.cn.
⁶ Department of Neurosurgery, Health Science Center, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, 518035, P. R. China. wpli@szu.edu.cn.
⁷ State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, P. R. China. ghma@ipe.ac.cn.
⁸ School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing, 100049, P. R. China. ghma@ipe.ac.cn.
⁹ State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, P. R. China. weiwei@ipe.ac.cn.
¹⁰ School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing, 100049, P. R. China. weiwei@ipe.ac.cn.

Abstract

Glioblastoma multiforme (GBM) is an aggressive brain cancer with a poor prognosis and few treatment options. Here, building on the observation of elevated lactate (LA) in resected GBM, we develop biomimetic therapeutic nanoparticles (NPs) that deliver agents for LA metabolism-based synergistic therapy. Because our self-assembling NPs are encapsulated in membranes derived from glioma cells, they readily penetrate the blood-brain barrier and target GBM through homotypic recognition. After reaching the tumors, lactate oxidase in the NPs converts LA into pyruvic acid (PA) and hydrogen peroxide (H₂O₂). The PA inhibits cancer cell growth by blocking histones expression and inducing cell-cycle arrest. In parallel, the H₂O₂ reacts with the delivered bis[2,4,5-trichloro-6-(pentyloxycarbonyl)phenyl] oxalate to release energy, which is used by the co-delivered photosensitizer chlorin e6 for the generation of cytotoxic singlet oxygen to kill glioma cells. Such a synergism ensures strong therapeutic effects against both glioma cell-line derived and patient-derived xenograft models.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomimetics
Brain Neoplasms* / drug therapy
Brain Neoplasms* / pathology
Cell Line, Tumor
Glioblastoma* / drug therapy
Glioblastoma* / pathology
Glioma*
Humans
Hydrogen Peroxide
Nanoparticles*

Substances

Hydrogen Peroxide

Associated data

figshare/10.6084/m9.figshare.19825075.v1
figshare/10.6084/m9.figshare.19825096.v1