Mitochondrion-specific dendritic lipopeptide liposomes for targeted sub-cellular delivery

Abstract The mitochondrion is an important sub-cellular organelle responsible for the cellular energetic source and processes. Owing to its unique sensitivity to heat and reactive oxygen species, the mitochondrion is an appropriate target for photothermal and photodynamic treatment for cancer. Howev...

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Main Authors: Lei Jiang, Sensen Zhou, Xiaoke Zhang, Cheng Li, Shilu Ji, Hui Mao, Xiqun Jiang
Format: Article
Language:English
Published: Nature Portfolio 2021-04-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-021-22594-2
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author Lei Jiang
Sensen Zhou
Xiaoke Zhang
Cheng Li
Shilu Ji
Hui Mao
Xiqun Jiang
author_facet Lei Jiang
Sensen Zhou
Xiaoke Zhang
Cheng Li
Shilu Ji
Hui Mao
Xiqun Jiang
author_sort Lei Jiang
collection DOAJ
description Abstract The mitochondrion is an important sub-cellular organelle responsible for the cellular energetic source and processes. Owing to its unique sensitivity to heat and reactive oxygen species, the mitochondrion is an appropriate target for photothermal and photodynamic treatment for cancer. However, targeted delivery of therapeutics to mitochondria remains a great challenge due to their location in the sub-cellular compartment and complexity of the intracellular environment. Herein, we report a class of the mitochondrion-targeted liposomal delivery platform consisting of a guanidinium-based dendritic peptide moiety mimicking mitochondrion protein transmembrane signaling to exert mitochondrion-targeted delivery with pH sensitive and charge-reversible functions to enhance tumor accumulation and cell penetration. Compared to the current triphenylphosphonium (TPP)-based mitochondrion targeting system, this dendritic lipopeptide (DLP) liposomal delivery platform exhibits about 3.7-fold higher mitochondrion-targeted delivery efficacy. Complete tumor eradication is demonstrated in mice bearing 4T1 mammary tumors after combined photothermal and photodynamic therapies delivered by the reported DLP platform.
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institution Kabale University
issn 2041-1723
language English
publishDate 2021-04-01
publisher Nature Portfolio
record_format Article
series Nature Communications
spelling doaj-art-b523e89cd2e14554af8523e7a2b398492025-08-20T03:27:18ZengNature PortfolioNature Communications2041-17232021-04-0112111210.1038/s41467-021-22594-2Mitochondrion-specific dendritic lipopeptide liposomes for targeted sub-cellular deliveryLei Jiang0Sensen Zhou1Xiaoke Zhang2Cheng Li3Shilu Ji4Hui Mao5Xiqun Jiang6MOE Key Laboratory of High Performance Polymer Materials and Technology, and Department of Polymer Science and Engineering, College of Chemistry and Chemical Engineering, Nanjing UniversityMOE Key Laboratory of High Performance Polymer Materials and Technology, and Department of Polymer Science and Engineering, College of Chemistry and Chemical Engineering, Nanjing UniversityMOE Key Laboratory of High Performance Polymer Materials and Technology, and Department of Polymer Science and Engineering, College of Chemistry and Chemical Engineering, Nanjing UniversityMOE Key Laboratory of High Performance Polymer Materials and Technology, and Department of Polymer Science and Engineering, College of Chemistry and Chemical Engineering, Nanjing UniversityMOE Key Laboratory of High Performance Polymer Materials and Technology, and Department of Polymer Science and Engineering, College of Chemistry and Chemical Engineering, Nanjing UniversityDepartment of Radiology and Imaging Sciences, Emory UniversityMOE Key Laboratory of High Performance Polymer Materials and Technology, and Department of Polymer Science and Engineering, College of Chemistry and Chemical Engineering, Nanjing UniversityAbstract The mitochondrion is an important sub-cellular organelle responsible for the cellular energetic source and processes. Owing to its unique sensitivity to heat and reactive oxygen species, the mitochondrion is an appropriate target for photothermal and photodynamic treatment for cancer. However, targeted delivery of therapeutics to mitochondria remains a great challenge due to their location in the sub-cellular compartment and complexity of the intracellular environment. Herein, we report a class of the mitochondrion-targeted liposomal delivery platform consisting of a guanidinium-based dendritic peptide moiety mimicking mitochondrion protein transmembrane signaling to exert mitochondrion-targeted delivery with pH sensitive and charge-reversible functions to enhance tumor accumulation and cell penetration. Compared to the current triphenylphosphonium (TPP)-based mitochondrion targeting system, this dendritic lipopeptide (DLP) liposomal delivery platform exhibits about 3.7-fold higher mitochondrion-targeted delivery efficacy. Complete tumor eradication is demonstrated in mice bearing 4T1 mammary tumors after combined photothermal and photodynamic therapies delivered by the reported DLP platform.https://doi.org/10.1038/s41467-021-22594-2
spellingShingle Lei Jiang
Sensen Zhou
Xiaoke Zhang
Cheng Li
Shilu Ji
Hui Mao
Xiqun Jiang
Mitochondrion-specific dendritic lipopeptide liposomes for targeted sub-cellular delivery
Nature Communications
title Mitochondrion-specific dendritic lipopeptide liposomes for targeted sub-cellular delivery
title_full Mitochondrion-specific dendritic lipopeptide liposomes for targeted sub-cellular delivery
title_fullStr Mitochondrion-specific dendritic lipopeptide liposomes for targeted sub-cellular delivery
title_full_unstemmed Mitochondrion-specific dendritic lipopeptide liposomes for targeted sub-cellular delivery
title_short Mitochondrion-specific dendritic lipopeptide liposomes for targeted sub-cellular delivery
title_sort mitochondrion specific dendritic lipopeptide liposomes for targeted sub cellular delivery
url https://doi.org/10.1038/s41467-021-22594-2
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AT sensenzhou mitochondrionspecificdendriticlipopeptideliposomesfortargetedsubcellulardelivery
AT xiaokezhang mitochondrionspecificdendriticlipopeptideliposomesfortargetedsubcellulardelivery
AT chengli mitochondrionspecificdendriticlipopeptideliposomesfortargetedsubcellulardelivery
AT shiluji mitochondrionspecificdendriticlipopeptideliposomesfortargetedsubcellulardelivery
AT huimao mitochondrionspecificdendriticlipopeptideliposomesfortargetedsubcellulardelivery
AT xiqunjiang mitochondrionspecificdendriticlipopeptideliposomesfortargetedsubcellulardelivery