Upconversion Nanoparticle-Based Cell Membrane-Coated cRGD Peptide Bioorthogonally Labeled Nanoplatform for Glioblastoma Treatment

Jingxin Mo; Xianjue Chen; Meiying Li; Wenxu Liu; Wei Zhao; Lee Yong Lim; Richard D Tilley; J Justin Gooding; Qinghua Li

doi:10.1021/acsami.2c11284

Upconversion Nanoparticle-Based Cell Membrane-Coated cRGD Peptide Bioorthogonally Labeled Nanoplatform for Glioblastoma Treatment

ACS Appl Mater Interfaces. 2022 Oct 27. doi: 10.1021/acsami.2c11284. Online ahead of print.

Authors

Jingxin Mo^{1

2

3}, Xianjue Chen⁴, Meiying Li^{1

5}, Wenxu Liu^{1

5}, Wei Zhao⁶, Lee Yong Lim⁷, Richard D Tilley², J Justin Gooding², Qinghua Li^{1

8

9

10

11}

Affiliations

¹ Guangxi Clinical Research Center for Neurological Diseases, The Affiliated Hospital of Guilin Medical University, Guilin 541001, China.
² School of Chemistry and Australian Centre for NanoMedicine, University of New South Wales, Sydney, New South Wales 2052, Australia.
³ Laboratory of Neurology, The Affiliated Hospital of Guilin Medical University, Guilin 541001, China.
⁴ School of Environmental and Life Sciences, University of Newcastle, Callaghan, New South Wales 2308, Australia.
⁵ School of Pharmacy, Guilin Medical University, Guilin 541001, China.
⁶ Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou 510080, China.
⁷ School of Allied Health, University of Western Australia, Perth, Western Australia 6009, Australia.
⁸ Department of Neurology, The Affiliated Hospital of Guilin Medical University, Guilin 541001, China.
⁹ Key Laboratory of Brain and Cognition of Guangxi Province, Guilin Medical University, Guilin 541001, China.
¹⁰ Guangxi Engineering Research Center for Digital Medicine and Clinical Translation, Guilin Medical University, Guilin 541001, China.
¹¹ Guangxi Key Laboratory of Big Data Intelligent Cloud Management for Neurological Diseases, Guilin Medical University, Guilin 541001, China.

PMID: 36300690
DOI: 10.1021/acsami.2c11284

Abstract

Glioblastoma is hard to be eradicated partly because of the obstructive blood-brain barrier (BBB) and the dynamic autophagy activities of glioblastoma. Here, hydroxychloroquine (HDX)-loaded yolk-shell upconversion nanoparticle (UCNP)@Zn_0.5Cd_0.5S nanoparticle coating with the cyclic Arg-Gly-Asp (cRGD)-grafted glioblastoma cell membrane for near-infrared (NIR)-triggered treatment of glioblastoma is prepared for the first time. UCNPs@Zn_0.5Cd_0.5S (abbreviated as YSN, yolk-shell nanoparticle) under NIR radiation will generate reactive oxygen species for imposing cytotoxicity. HDX, the only available autophagy inhibitor in clinical studies, can enhance cytotoxicity by preventing damaged organelles from being recycled. The cRGD-decorated cell membrane allowed the HDX-loaded nanoparticles to efficiently bypass the BBB and specifically target glioblastoma cells. Exceptional treatment efficacy of the NIR-triggered chemotherapy and photodynamic therapy was achieved in U87 cells and in the mouse glioblastoma model as well. Our results provided proof-of-concept evidence that HDX@YSN@CCM@cRGD could overcome the delivery barriers and achieve targeted treatment of glioblastoma.

Keywords: cRGD bioorthogonal labeling; glioblastoma; near-infrared; upconversion nanoparticle; yolk−shell structure.