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Delivery of Chemotherapy Agents and Nucleic Acids with pH-Dependent Nanoparticles

With less than one percent of systemically injected nanoparticles accumulating in tumors, several novel approaches have been spurred to direct and release the therapy in or near tumors. One such approach depends on the acidic pH of the extracellular matrix and endosomes of the tumor. With an average...

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Autores principales: Leng, Qixin, Imtiyaz, Zuha, Woodle, Martin C., Mixson, A. James
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10222096/
https://www.ncbi.nlm.nih.gov/pubmed/37242725
http://dx.doi.org/10.3390/pharmaceutics15051482
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author Leng, Qixin
Imtiyaz, Zuha
Woodle, Martin C.
Mixson, A. James
author_facet Leng, Qixin
Imtiyaz, Zuha
Woodle, Martin C.
Mixson, A. James
author_sort Leng, Qixin
collection PubMed
description With less than one percent of systemically injected nanoparticles accumulating in tumors, several novel approaches have been spurred to direct and release the therapy in or near tumors. One such approach depends on the acidic pH of the extracellular matrix and endosomes of the tumor. With an average pH of 6.8, the extracellular tumor matrix provides a gradient for pH-responsive particles to accumulate, enabling greater specificity. Upon uptake by tumor cells, nanoparticles are further exposed to lower pHs, reaching a pH of 5 in late endosomes. Based on these two acidic environments in the tumor, various pH-dependent targeting strategies have been employed to release chemotherapy or the combination of chemotherapy and nucleic acids from macromolecules such as the keratin protein or polymeric nanoparticles. We will review these release strategies, including pH-sensitive linkages between the carrier and hydrophobic chemotherapy agent, the protonation and disruption of polymeric nanoparticles, an amalgam of these first two approaches, and the release of polymers shielding drug-loaded nanoparticles. While several pH-sensitive strategies have demonstrated marked antitumor efficacy in preclinical trials, many studies are early in their development with several obstacles that may limit their clinical use.
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spelling pubmed-102220962023-05-28 Delivery of Chemotherapy Agents and Nucleic Acids with pH-Dependent Nanoparticles Leng, Qixin Imtiyaz, Zuha Woodle, Martin C. Mixson, A. James Pharmaceutics Review With less than one percent of systemically injected nanoparticles accumulating in tumors, several novel approaches have been spurred to direct and release the therapy in or near tumors. One such approach depends on the acidic pH of the extracellular matrix and endosomes of the tumor. With an average pH of 6.8, the extracellular tumor matrix provides a gradient for pH-responsive particles to accumulate, enabling greater specificity. Upon uptake by tumor cells, nanoparticles are further exposed to lower pHs, reaching a pH of 5 in late endosomes. Based on these two acidic environments in the tumor, various pH-dependent targeting strategies have been employed to release chemotherapy or the combination of chemotherapy and nucleic acids from macromolecules such as the keratin protein or polymeric nanoparticles. We will review these release strategies, including pH-sensitive linkages between the carrier and hydrophobic chemotherapy agent, the protonation and disruption of polymeric nanoparticles, an amalgam of these first two approaches, and the release of polymers shielding drug-loaded nanoparticles. While several pH-sensitive strategies have demonstrated marked antitumor efficacy in preclinical trials, many studies are early in their development with several obstacles that may limit their clinical use. MDPI 2023-05-12 /pmc/articles/PMC10222096/ /pubmed/37242725 http://dx.doi.org/10.3390/pharmaceutics15051482 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Leng, Qixin
Imtiyaz, Zuha
Woodle, Martin C.
Mixson, A. James
Delivery of Chemotherapy Agents and Nucleic Acids with pH-Dependent Nanoparticles
title Delivery of Chemotherapy Agents and Nucleic Acids with pH-Dependent Nanoparticles
title_full Delivery of Chemotherapy Agents and Nucleic Acids with pH-Dependent Nanoparticles
title_fullStr Delivery of Chemotherapy Agents and Nucleic Acids with pH-Dependent Nanoparticles
title_full_unstemmed Delivery of Chemotherapy Agents and Nucleic Acids with pH-Dependent Nanoparticles
title_short Delivery of Chemotherapy Agents and Nucleic Acids with pH-Dependent Nanoparticles
title_sort delivery of chemotherapy agents and nucleic acids with ph-dependent nanoparticles
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10222096/
https://www.ncbi.nlm.nih.gov/pubmed/37242725
http://dx.doi.org/10.3390/pharmaceutics15051482
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