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Macromolecular Drug Carriers for Targeted Glioblastoma Therapy: Preclinical Studies, Challenges, and Future Perspectives
Glioblastoma, the most common, aggressive brain tumor, ranks among the least curable cancers—owing to its strong tendency for intracranial dissemination, high proliferation potential, and inherent tumor resistance to radiation and chemotherapy. Current glioblastoma treatment strategies are further h...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6304427/ https://www.ncbi.nlm.nih.gov/pubmed/30619758 http://dx.doi.org/10.3389/fonc.2018.00624 |
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author | Raucher, Drazen Dragojevic, Sonja Ryu, Jungsu |
author_facet | Raucher, Drazen Dragojevic, Sonja Ryu, Jungsu |
author_sort | Raucher, Drazen |
collection | PubMed |
description | Glioblastoma, the most common, aggressive brain tumor, ranks among the least curable cancers—owing to its strong tendency for intracranial dissemination, high proliferation potential, and inherent tumor resistance to radiation and chemotherapy. Current glioblastoma treatment strategies are further hampered by a critical challenge: adverse, non-specific treatment effects in normal tissue combined with the inability of drugs to penetrate the blood brain barrier and reach the tumor microenvironment. Thus, the creation of effective therapies for glioblastoma requires development of targeted drug-delivery systems that increase accumulation of the drug in the tumor tissue while minimizing systemic toxicity in healthy tissues. As demonstrated in various preclinical glioblastoma models, macromolecular drug carriers have the potential to improve delivery of small molecule drugs, therapeutic peptides, proteins, and genes to brain tumors. Currently used macromolecular drug delivery systems, such as liposomes and polymers, passively target solid tumors, including glioblastoma, by capitalizing on abnormalities of the tumor vasculature, its lack of lymphatic drainage, and the enhanced permeation and retention (EPR) effect. In addition to passive targeting, active targeting approaches include the incorporation of various ligands on the surface of macromolecules that bind to cell surface receptors expressed on specific cancer cells. Active targeting approaches also utilize stimulus responsive macromolecules which further improve tumor accumulation by triggering changes in the physical properties of the macromolecular carrier. The stimulus can be an intrinsic property of the tumor tissue, such as low pH, or extrinsic, such as local application of ultrasound or heat. This review article explores current preclinical studies and future perspectives of targeted drug delivery to glioblastoma by macromolecular carrier systems, including polymeric micelles, nanoparticles, and biopolymers. We highlight key aspects of the design of diverse macromolecular drug delivery systems through a review of their preclinical applications in various glioblastoma animal models. We also review the principles and advantages of passive and active targeting based on various macromolecular carriers. Additionally, we discuss the potential disadvantages that may prevent clinical application of these carriers in targeting glioblastoma, as well as approaches to overcoming these obstacles. |
format | Online Article Text |
id | pubmed-6304427 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-63044272019-01-07 Macromolecular Drug Carriers for Targeted Glioblastoma Therapy: Preclinical Studies, Challenges, and Future Perspectives Raucher, Drazen Dragojevic, Sonja Ryu, Jungsu Front Oncol Oncology Glioblastoma, the most common, aggressive brain tumor, ranks among the least curable cancers—owing to its strong tendency for intracranial dissemination, high proliferation potential, and inherent tumor resistance to radiation and chemotherapy. Current glioblastoma treatment strategies are further hampered by a critical challenge: adverse, non-specific treatment effects in normal tissue combined with the inability of drugs to penetrate the blood brain barrier and reach the tumor microenvironment. Thus, the creation of effective therapies for glioblastoma requires development of targeted drug-delivery systems that increase accumulation of the drug in the tumor tissue while minimizing systemic toxicity in healthy tissues. As demonstrated in various preclinical glioblastoma models, macromolecular drug carriers have the potential to improve delivery of small molecule drugs, therapeutic peptides, proteins, and genes to brain tumors. Currently used macromolecular drug delivery systems, such as liposomes and polymers, passively target solid tumors, including glioblastoma, by capitalizing on abnormalities of the tumor vasculature, its lack of lymphatic drainage, and the enhanced permeation and retention (EPR) effect. In addition to passive targeting, active targeting approaches include the incorporation of various ligands on the surface of macromolecules that bind to cell surface receptors expressed on specific cancer cells. Active targeting approaches also utilize stimulus responsive macromolecules which further improve tumor accumulation by triggering changes in the physical properties of the macromolecular carrier. The stimulus can be an intrinsic property of the tumor tissue, such as low pH, or extrinsic, such as local application of ultrasound or heat. This review article explores current preclinical studies and future perspectives of targeted drug delivery to glioblastoma by macromolecular carrier systems, including polymeric micelles, nanoparticles, and biopolymers. We highlight key aspects of the design of diverse macromolecular drug delivery systems through a review of their preclinical applications in various glioblastoma animal models. We also review the principles and advantages of passive and active targeting based on various macromolecular carriers. Additionally, we discuss the potential disadvantages that may prevent clinical application of these carriers in targeting glioblastoma, as well as approaches to overcoming these obstacles. Frontiers Media S.A. 2018-12-17 /pmc/articles/PMC6304427/ /pubmed/30619758 http://dx.doi.org/10.3389/fonc.2018.00624 Text en Copyright © 2018 Raucher, Dragojevic and Ryu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Raucher, Drazen Dragojevic, Sonja Ryu, Jungsu Macromolecular Drug Carriers for Targeted Glioblastoma Therapy: Preclinical Studies, Challenges, and Future Perspectives |
title | Macromolecular Drug Carriers for Targeted Glioblastoma Therapy: Preclinical Studies, Challenges, and Future Perspectives |
title_full | Macromolecular Drug Carriers for Targeted Glioblastoma Therapy: Preclinical Studies, Challenges, and Future Perspectives |
title_fullStr | Macromolecular Drug Carriers for Targeted Glioblastoma Therapy: Preclinical Studies, Challenges, and Future Perspectives |
title_full_unstemmed | Macromolecular Drug Carriers for Targeted Glioblastoma Therapy: Preclinical Studies, Challenges, and Future Perspectives |
title_short | Macromolecular Drug Carriers for Targeted Glioblastoma Therapy: Preclinical Studies, Challenges, and Future Perspectives |
title_sort | macromolecular drug carriers for targeted glioblastoma therapy: preclinical studies, challenges, and future perspectives |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6304427/ https://www.ncbi.nlm.nih.gov/pubmed/30619758 http://dx.doi.org/10.3389/fonc.2018.00624 |
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