Biomimetic nanocarriers loaded with temozolomide by cloaking brain-targeting peptides for targeting drug delivery system to promote anticancer effects in glioblastoma cells

Huaming Chen; Yunhong Wang; Hai Wang; Kun Zhang; Yunfei Liu; Qiangfeng Li; Chengli Li; Zhonghui Wen; Ziyu Chen

doi:10.1016/j.heliyon.2024.e28256

Biomimetic nanocarriers loaded with temozolomide by cloaking brain-targeting peptides for targeting drug delivery system to promote anticancer effects in glioblastoma cells

Heliyon. 2024 Mar 15;10(7):e28256. doi: 10.1016/j.heliyon.2024.e28256. eCollection 2024 Apr 15.

Authors

Huaming Chen¹, Yunhong Wang¹, Hai Wang¹, Kun Zhang², Yunfei Liu³, Qiangfeng Li¹, Chengli Li¹, Zhonghui Wen¹, Ziyu Chen⁴

Affiliations

¹ Department of Neurosurgery, Pu'er People's Hospital, Pu'er, 665099, China.
² Department of Emergency, Pu'er People's Hospital, Pu'er, 665099, China.
³ Department of Ultrasound Medicine, Pu'er People's Hospital, Pu'er, 665099, China.
⁴ Department of Nephrology, Pu'er People's Hospital, Pu'er, 665099, China.

Abstract

Glioma is the leading cancer of the central nervous system (CNS). The efficacy of glioma treatment is significantly hindered by the presence of the blood-brain barrier (BBB) and blood-brain tumour barrier (BBTB), which prevent most drugs from entering the brain and tumours. Hence, we established a novel drug delivery nanosystem of brain tumour-targeting that could self-assemble the method using an amphiphilic Zein protein isolated from corn. Zein's amphiphilicity prompted it to self-assembled into NPs, efficiently containing TMZ. This allowed us to investigate temozolomide (TMZ) for glioblastoma (GBM) treatment. To construct TMZ-encapsulated NPs (TMZ@RVG-Zein NPs), the NPs' Zein was clocked to rabies virus glycoprotein 29 (RVG29). To verify that the NPs could penetrate the BBB and precisely target and kill the GBM cancer cell line, in vitro studies were performed. The process of NPs penetrating cancer cell membranes was investigated using enzyme-linked immunosorbent assays (ELISAs) to measure the expressions of nicotinic acetylcholine receptors (nAChRs) on the U87 cell line. Therefore, effective targeted brain cancer treatment is possible by forming NP clocks, a cell-penetrating natural Zein protein with an RVG29. These NPs can penetrate the blood-brain barrier (BBB) and enter the glioblastoma (U87) cell line to release TMZ. These NPs have a distinct cocktail of biocompatibility and brain-targeting abilities, making them ideal for involving brain diseases.

Keywords: Apoptosis; Blood-brain barrier; Glioblastoma; Temozolomide; Zein.