Mitochondria-Targeting and ROS-Responsive Nanocarriers via Amphiphilic TPP-PEG-TK-Ce6 for Nanoenabled Photodynamic Therapy

Designing targeted-delivering and stimuli-responsive nanocarriers for photodynamic therapy (PDT) is an appealing method, especially, targeting delivery of photosensitizers to mitochondria as the most sensitive cellular organelles to reactive oxygen species (ROS) could significantly enhance the thera...

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Main Authors: Yangjian Wang, Junshui Zheng, Jian Lin, Kai Ye, Peng Wei
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Advances in Polymer Technology
Online Access:http://dx.doi.org/10.1155/2022/1178039
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author Yangjian Wang
Junshui Zheng
Jian Lin
Kai Ye
Peng Wei
author_facet Yangjian Wang
Junshui Zheng
Jian Lin
Kai Ye
Peng Wei
author_sort Yangjian Wang
collection DOAJ
description Designing targeted-delivering and stimuli-responsive nanocarriers for photodynamic therapy (PDT) is an appealing method, especially, targeting delivery of photosensitizers to mitochondria as the most sensitive cellular organelles to reactive oxygen species (ROS) could significantly enhance the therapeutic efficacy of PDT. In this study, we synthesized triphenylphosphonium bonded PEG-NH2 (TPP-PEG-NH2) and bridged to chlorin e6 (Ce6) via thioketal (TK) linkage to obtain red light-triggered, amphiphilic copolymer (TPP-PEG-TK-Ce6), which could self-assemble into micelles with an average size of 160 nm and zeta potential of +20.1 mV. The in vitro release behavior of TPP-PEG-TK-Ce6 nanocarriers showed a light-activated way and was dependent on the H2O2 concentration. TPP-PEG-TK-Ce6 nanocarriers exhibited high cytotoxicity against C6 cells with illumination. Confocal laser scanning microscopy observation indicated that TPP-PEG-TK-Ce6 nanocarriers were efficiently internalized into the mitochondrion of C6 cells, released Ce6 via light activated. By contrast, in the case of TPP-PEG-NH2 directly bonded Ce6 (TPP-PEG-Ce6) nanocarriers, little Ce6 was found in the mitochondrion. The stronger fluorescence in the mitochondrion of TPP-PEG-TK-Ce6 nanocarriers originated from the mitochondrial-targeting capability of TPP and the cleavage of TK linkages activated by light irradiation, which greatly improved the cellular uptake of TPP-PEG-TK-Ce6 nanocarriers and released more Ce6 in the mitochondrion. This work provided a facile strategy to improve PDT efficacy.
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spelling doaj-art-05c7286aea24473fb8a8b37362cc08fc2025-08-20T02:03:00ZengWileyAdvances in Polymer Technology1098-23292022-01-01202210.1155/2022/1178039Mitochondria-Targeting and ROS-Responsive Nanocarriers via Amphiphilic TPP-PEG-TK-Ce6 for Nanoenabled Photodynamic TherapyYangjian Wang0Junshui Zheng1Jian Lin2Kai Ye3Peng Wei4Reparative and Reconstructive SurgerySchool of MedicineSchool of MedicineSchool of MedicineReparative and Reconstructive SurgeryDesigning targeted-delivering and stimuli-responsive nanocarriers for photodynamic therapy (PDT) is an appealing method, especially, targeting delivery of photosensitizers to mitochondria as the most sensitive cellular organelles to reactive oxygen species (ROS) could significantly enhance the therapeutic efficacy of PDT. In this study, we synthesized triphenylphosphonium bonded PEG-NH2 (TPP-PEG-NH2) and bridged to chlorin e6 (Ce6) via thioketal (TK) linkage to obtain red light-triggered, amphiphilic copolymer (TPP-PEG-TK-Ce6), which could self-assemble into micelles with an average size of 160 nm and zeta potential of +20.1 mV. The in vitro release behavior of TPP-PEG-TK-Ce6 nanocarriers showed a light-activated way and was dependent on the H2O2 concentration. TPP-PEG-TK-Ce6 nanocarriers exhibited high cytotoxicity against C6 cells with illumination. Confocal laser scanning microscopy observation indicated that TPP-PEG-TK-Ce6 nanocarriers were efficiently internalized into the mitochondrion of C6 cells, released Ce6 via light activated. By contrast, in the case of TPP-PEG-NH2 directly bonded Ce6 (TPP-PEG-Ce6) nanocarriers, little Ce6 was found in the mitochondrion. The stronger fluorescence in the mitochondrion of TPP-PEG-TK-Ce6 nanocarriers originated from the mitochondrial-targeting capability of TPP and the cleavage of TK linkages activated by light irradiation, which greatly improved the cellular uptake of TPP-PEG-TK-Ce6 nanocarriers and released more Ce6 in the mitochondrion. This work provided a facile strategy to improve PDT efficacy.http://dx.doi.org/10.1155/2022/1178039
spellingShingle Yangjian Wang
Junshui Zheng
Jian Lin
Kai Ye
Peng Wei
Mitochondria-Targeting and ROS-Responsive Nanocarriers via Amphiphilic TPP-PEG-TK-Ce6 for Nanoenabled Photodynamic Therapy
Advances in Polymer Technology
title Mitochondria-Targeting and ROS-Responsive Nanocarriers via Amphiphilic TPP-PEG-TK-Ce6 for Nanoenabled Photodynamic Therapy
title_full Mitochondria-Targeting and ROS-Responsive Nanocarriers via Amphiphilic TPP-PEG-TK-Ce6 for Nanoenabled Photodynamic Therapy
title_fullStr Mitochondria-Targeting and ROS-Responsive Nanocarriers via Amphiphilic TPP-PEG-TK-Ce6 for Nanoenabled Photodynamic Therapy
title_full_unstemmed Mitochondria-Targeting and ROS-Responsive Nanocarriers via Amphiphilic TPP-PEG-TK-Ce6 for Nanoenabled Photodynamic Therapy
title_short Mitochondria-Targeting and ROS-Responsive Nanocarriers via Amphiphilic TPP-PEG-TK-Ce6 for Nanoenabled Photodynamic Therapy
title_sort mitochondria targeting and ros responsive nanocarriers via amphiphilic tpp peg tk ce6 for nanoenabled photodynamic therapy
url http://dx.doi.org/10.1155/2022/1178039
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