Peptide-22 and Cyclic RGD Functionalized Liposomes for Glioma Targeting Drug Delivery Overcoming BBB and BBTB

Abstract

Chemotherapy outcomes for the treatment of glioma remain unsatisfied due to the inefficient drug transport across BBB/BBTB and poor drug accumulation in the tumor site. Nanocarriers functionalized with different targeting ligands are considered as one of the most promising alternatives. However, few studies were reported to compare the targeting efficiency of the ligands and develop nanoparticles to realize BBB/BBTB crossing and brain tumor targeting simultaneously. In this study, six peptide-based ligands (Angiopep-2, T7, Peptide-22, c(RGDfK), D-SP5 and Pep-1), widely used for brain delivery, were selected to decorate liposomes, respectively, so as to compare their targeting ability to BBB or BBTB. Based on the in vitro cellular uptake results on BCECs and HUVECs, Peptide-22 and c(RGDfK) were picked to construct a BBB/BBTB dual-crossing, glioma-targeting liposomal drug delivery system c(RGDfK)/Pep-22-DOX-LP. In vitro cellular uptake demonstrated that the synergetic effect of c(RGDfK) and Peptide-22 could significantly increase the internalization of liposomes on U87 cells. In vivo imaging further verified that c(RGDfK)/Pep-22-LP exhibited higher brain tumor distribution than single ligand modified liposomes. The median survival time of glioma-bearing mice treated with c(RGDfK)/Pep-22-DOX-LP (39.5 days) was significantly prolonged than those treated with free doxorubicin or other controls. In conclusion, the c(RGDfK) and Peptide-22 dual-modified liposome was constructed based on the targeting ability screening of various ligands. The system could effectively overcome BBB/BBTB barriers, target to tumor cells and inhibit the growth of glioma, which proved its potential for improving the efficacy of chemotherapeutics for glioma therapy.

Recent Advances in Targeted Tumor Chemotherapy Based on Smart Nanomedicines

“…So the PTX‐loaded micelles exhibited enhanced antiglioma efficacy in vitro and effectively prolonged survival time of glioma‐bearing mice. Duan and co‐workers designed a BBB/BBTB dual‐crossing, glioma‐targeting liposomal DDS, in which peptide‐22 and c(Arg‐Gly‐Asp‐d‐Phe‐Lys) separately targeted BBB and BBTB . The system could significantly overcome BBB/BBTB barriers, target to tumor cells, and inhibit the growth of glioma.…”

“…Duan and co-workers designed a BBB/BBTB dual-crossing, glioma-targeting liposomal DDS, in which peptide-22 and c(Arg-Gly-Asp-d-Phe-Lys) separately targeted BBB and BBTB. [69] The system could significantly overcome BBB/BBTB barriers, target to tumor cells, and inhibit the growth of glioma.…”

Synergistic effects of liposomes encapsulating atorvastatin calcium and curcumin and targeting dysfunctional endothelial cells in reducing atherosclerosis

“…29,30 For example, liposomes decorated with targeting ligand (eg, folate or cyclic Arg-Gly-Asp [RGD] peptide) can effectively deliver drug into the nidus position using an active targeting delivery mechanism, resulting in the desired therapeutic effects and minimal side effects. [31][32][33][34] Notably, integration of co-delivery and targeted delivery in one nanosystem could significantly strengthen anti-atherosclerosis effects and reduce adverse effects. To achieve targeted delivery of Ato and Cur to inflamed/ dysfunctional ECs, target epitopes, specifically upregulated on the surface of diseased ECs, can be targeted by specific antibody-conjugated nanomedicines, effectively shuttling cargos into inflamed ECs.…”

Preparation and evaluation of 2-methoxyestradiol-loaded pH-sensitive liposomes

“…However, liposomes easily leak drugs in physiological environments, which is not a conducive phenomenon because it could not leads to drug aggregation in tumor sites (Wang et al, 2017). In order to improve the liposome therapeutic efficacy, multifunction liposomes have been designed (Dai et al, 2014;Chen et al, 2017;Chi et al, 2017;Dai et al, 2017). Considering that the pH value of the tumor tissue (about 5.0) is lower than that of the normal tissue, pH-sensitive liposomes have been developed as an efficient system for controlled drug release to improve drug efficacy after intravenous administration Lee, Thompson, 2017).…”