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Charge Conversion Polymer–Liposome Complexes to Overcome the Limitations of Cationic Liposomes in Mitochondrial-Targeting Drug Delivery

Mitochondrial-targeting therapy is considered an important strategy for cancer treatment. (3-Carboxypropyl) triphenyl phosphonium (CTPP) is one of the candidate molecules that can drive drugs or nanomedicines to target mitochondria via electrostatic interactions. However, the mitochondrial-targeting...

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Autores principales: Shueng, Pei-Wei, Yu, Lu-Yi, Hou, Hsiao-Hsin, Chiu, Hsin-Cheng, Lo, Chun-Liang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8954455/
https://www.ncbi.nlm.nih.gov/pubmed/35328500
http://dx.doi.org/10.3390/ijms23063080
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author Shueng, Pei-Wei
Yu, Lu-Yi
Hou, Hsiao-Hsin
Chiu, Hsin-Cheng
Lo, Chun-Liang
author_facet Shueng, Pei-Wei
Yu, Lu-Yi
Hou, Hsiao-Hsin
Chiu, Hsin-Cheng
Lo, Chun-Liang
author_sort Shueng, Pei-Wei
collection PubMed
description Mitochondrial-targeting therapy is considered an important strategy for cancer treatment. (3-Carboxypropyl) triphenyl phosphonium (CTPP) is one of the candidate molecules that can drive drugs or nanomedicines to target mitochondria via electrostatic interactions. However, the mitochondrial-targeting effectiveness of CTPP is low. Therefore, pH-sensitive polymer–liposome complexes with charge-conversion copolymers and CTPP-containing cationic liposomes were designed for efficiently delivering an anti-cancer agent, ceramide, into cancer cellular mitochondria. The charge-conversion copolymers, methoxypoly(ethylene glycol)-block-poly(methacrylic acid-g-histidine), were anionic and helped in absorbing and shielding the positive charges of cationic liposomes at pH 7.4. In contrast, charge-conversion copolymers became neutral in order to depart from cationic liposomes and induced endosomal escape for releasing cationic liposomes into cytosol at acidic endosomes. The experimental results reveal that these pH-sensitive polymer–liposome complexes could rapidly escape from MCF-7 cell endosomes and target MCF-7 mitochondria within 3 h, thereby leading to the generation of reactive oxygen species and cell apoptosis. These findings provide a promising solution for cationic liposomes in cancer mitochondrial-targeting drug delivery.
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spelling pubmed-89544552022-03-26 Charge Conversion Polymer–Liposome Complexes to Overcome the Limitations of Cationic Liposomes in Mitochondrial-Targeting Drug Delivery Shueng, Pei-Wei Yu, Lu-Yi Hou, Hsiao-Hsin Chiu, Hsin-Cheng Lo, Chun-Liang Int J Mol Sci Article Mitochondrial-targeting therapy is considered an important strategy for cancer treatment. (3-Carboxypropyl) triphenyl phosphonium (CTPP) is one of the candidate molecules that can drive drugs or nanomedicines to target mitochondria via electrostatic interactions. However, the mitochondrial-targeting effectiveness of CTPP is low. Therefore, pH-sensitive polymer–liposome complexes with charge-conversion copolymers and CTPP-containing cationic liposomes were designed for efficiently delivering an anti-cancer agent, ceramide, into cancer cellular mitochondria. The charge-conversion copolymers, methoxypoly(ethylene glycol)-block-poly(methacrylic acid-g-histidine), were anionic and helped in absorbing and shielding the positive charges of cationic liposomes at pH 7.4. In contrast, charge-conversion copolymers became neutral in order to depart from cationic liposomes and induced endosomal escape for releasing cationic liposomes into cytosol at acidic endosomes. The experimental results reveal that these pH-sensitive polymer–liposome complexes could rapidly escape from MCF-7 cell endosomes and target MCF-7 mitochondria within 3 h, thereby leading to the generation of reactive oxygen species and cell apoptosis. These findings provide a promising solution for cationic liposomes in cancer mitochondrial-targeting drug delivery. MDPI 2022-03-12 /pmc/articles/PMC8954455/ /pubmed/35328500 http://dx.doi.org/10.3390/ijms23063080 Text en © 2022 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 Article
Shueng, Pei-Wei
Yu, Lu-Yi
Hou, Hsiao-Hsin
Chiu, Hsin-Cheng
Lo, Chun-Liang
Charge Conversion Polymer–Liposome Complexes to Overcome the Limitations of Cationic Liposomes in Mitochondrial-Targeting Drug Delivery
title Charge Conversion Polymer–Liposome Complexes to Overcome the Limitations of Cationic Liposomes in Mitochondrial-Targeting Drug Delivery
title_full Charge Conversion Polymer–Liposome Complexes to Overcome the Limitations of Cationic Liposomes in Mitochondrial-Targeting Drug Delivery
title_fullStr Charge Conversion Polymer–Liposome Complexes to Overcome the Limitations of Cationic Liposomes in Mitochondrial-Targeting Drug Delivery
title_full_unstemmed Charge Conversion Polymer–Liposome Complexes to Overcome the Limitations of Cationic Liposomes in Mitochondrial-Targeting Drug Delivery
title_short Charge Conversion Polymer–Liposome Complexes to Overcome the Limitations of Cationic Liposomes in Mitochondrial-Targeting Drug Delivery
title_sort charge conversion polymer–liposome complexes to overcome the limitations of cationic liposomes in mitochondrial-targeting drug delivery
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8954455/
https://www.ncbi.nlm.nih.gov/pubmed/35328500
http://dx.doi.org/10.3390/ijms23063080
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