Dual-Target Peptide-Modified Erythrocyte Membrane-Enveloped PLGA Nanoparticles for the Treatment of Glioma

Abstract

Penetration of the blood-brain barrier (BBB) and the blood-brain tumor barrier (BBTB) remains a significant challenge for the delivery of drugs in the treatment of glioma. Therefore, the development of targeted preparations with the ability to penetrate the BBB and BBTB, and target gliomas, is an important approach if we are to improve the efficacy of glioma treatment. In the current study, an active targeting preparation based on PLGA nanoparticles coated with erythrocyte membranes (RBCNPs) and dual-modified with D WSW and NGR peptide ligands (D WSW/NGR-RBCNPs). Euphorbia factor L1 (EFL1) extracted from euphorbiae semen was used as the model drug. The final nanoparticles were characterized by in vivo and in vitro tests. In vitro results showed that EFL1-loaded D WSW/NGR-RBCNPs were taken up by cells and had the ability to penetrate the BBB and BBTB and produce cytotoxic effects. Furthermore, in vivo studies in mice showed that when injected intravenously, these specialized NPs could enter the brain, target tumor tissue, and significantly extend life span. The results showed that dualtargeting EFL1-loaded D WSW/NGR-RBCNPs have significant potential as a nanotherapeutic tool for the treatment of brain glioma.

Chronicles of Nanoerythrosomes: An Erythrocyte-Based Biomimetic Smart Drug Delivery System as a Therapeutic and Diagnostic Tool in Cancer Therapy

“…Euphorbia factor-L1 was used as model drug, and these NPs were taken up by the cells and showed the ability to cross both BBB and BBTB, thereby producing cytotoxic effects in vitro. Furthermore, in vivo studies supported these results and the prepared NPs could enter the brain, targeting tumor tissues and significantly extending the life span [ 82 ]. Subsequently, NERs of 5-FU for liver cancer treatment were prepared for improved pharmacokinetic and biodistribution of 5-FU.…”

Cancer Cell Membrane-Coated Nanosuspensions for Enhanced Chemotherapeutic Treatment of Glioma

“…After the cells were injected, the needle was retained, for an extra 1 min, and then finally slowly pull out. After, the wound was sutured and the mice were fed normally [ 35 ].…”

Recent Advances in the Surface Functionalization of PLGA-Based Nanomedicines

“…Peptides have attracted a significant amount of interest as ligands due to their small size, low toxicity, lack of immunogenicity, high selectivity, and wide inter/intracellular [ 165 ]. Peptide-modified PLGA-based NPs have recently been shown to successfully target various diseases, such as cancer [ 166 , 167 ] and atherosclerotic plaques [ 118 ].…”

“…BBB-penetrating peptides, such as angiopep-2 peptide [ 174 ] and DWSW peptide [ 166 ], are exciting tools with which to target brain diseases. Preclinical studies of the systematic administration of these PLGA-based systems showed the ability of BBB-penetrating peptides to facilitate the entry of PLGA into the brain [ 166 ].…”