Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Enhanced Bbb and Bbtb Penetration and Improved Anti-Glioma Behavior of Bortezomib Through Dual-Targeting Nanostructured Lipid Carriers Publisher Pubmed



Farshbaf M1, 2, 3 ; Mojaradjabali S2, 4 ; Hemmati S2 ; Khosroushahi AY1, 2 ; Motasadizadeh H5, 6 ; Zarebkohan A1 ; Valizadeh H2, 4
Authors
Show Affiliations
Authors Affiliations
  1. 1. Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
  2. 2. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  3. 3. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
  4. 4. Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
  5. 5. Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

Source: Journal of Controlled Release Published:2022


Abstract

The effective treatment of glioma through conventional chemotherapy is proved to be a great challenge in clinics. The main reason is due to the existence of two physiological and pathological barriers respectively including the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) that prevent most of the chemotherapeutics from efficient delivery to the brain tumors. To address this challenge, an ideal drug delivery system would efficiently traverse the BBB and BBTB and deliver the therapeutics into the glioma cells with high selectivity. Herein, a targeted delivery system was developed based on nanostructured lipid carriers (NLCs) modified with two proteolytically stable D-peptides, D8 and RI-VAP (Dual NLCs). D8 possesses high affinity towards nicotine acetylcholine receptors (nAChRs), overexpressed on brain capillary endothelial cells (BCECs), and can penetrate through the BBB with high efficiency. RI-VAP is a specific ligand of cell surface GRP78 (csGRP78), a specific angiogenesis and cancer cell-surface marker, capable of circumventing the BBTB with superior glioma-homing property. Dual NLCs could internalize into BCECs, tumor neovascular endothelial cells, and glioma cells with high specificity and could penetrate through in vitro BBB and BBTB models with excellent efficiency compared to non-targeted or mono-targeted NLCs. In vivo whole-animal imaging and ex vivo imaging further confirmed the superior targeting capability of Dual NLCs towards intracranial glioma. When loaded with Bortezomib (BTZ), Dual NLCs attained the highest therapeutic efficiency by means of superior in vitro cytotoxicity and apoptosis and prolonged survival rate and efficient anti-glioma behavior in intracranial glioma bearing mice. Collectively, the designed targeting platform in this study could overcome multiple barriers and effectively deliver BTZ to glioma cells, which represent its potential for advanced brain cancer treatment with promising therapeutic outcomes. © 2022
Related Docs
1. Transferrin Receptor-Mediated Liposomal Drug Delivery: Recent Trends in Targeted Therapy of Cancer, Expert Opinion on Drug Delivery (2022)
2. An Update on Actively Targeted Liposomes in Advanced Drug Delivery to Glioma, International Journal of Pharmaceutics (2021)
3. Comparison of Three Synthetic Transferrin Mimetic Small Peptides to Promote the Blood–Brain Barrier Penetration of Vincristine Liposomes for Improved Glioma Targeted Therapy, International Journal of Pharmaceutics (2022)
4. The Impact of Protein Corona on the Biological Behavior of Targeting Nanomedicines, International Journal of Pharmaceutics (2022)
5. Recent Advances in Glioma Cancer Treatment: Conventional and Epigenetic Realms, Vaccines (2022)
Experts (# of related papers)
Fatemeh Atyabi (2)