A Self-Assembling Amphiphilic Peptide Dendrimer-Based Drug Delivery System for Cancer Therapy
Despite being a mainstay of clinical cancer treatment, chemotherapy is limited by its severe side effects and inherent or acquired drug resistance. Nanotechnology-based drug-delivery systems are widely expected to bring new hope for cancer therapy. These systems exploit the ability of nanomaterials...
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MDPI AG
2021-07-01
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Series: | Pharmaceutics |
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Online Access: | https://www.mdpi.com/1999-4923/13/7/1092 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dandan Zhu Huanle Zhang Yuanzheng Huang Baoping Lian Chi Ma Lili Han Yu Chen Shengmei Wu Ning Li Wenjie Zhang Xiaoxuan Liu |
spellingShingle |
Dandan Zhu Huanle Zhang Yuanzheng Huang Baoping Lian Chi Ma Lili Han Yu Chen Shengmei Wu Ning Li Wenjie Zhang Xiaoxuan Liu A Self-Assembling Amphiphilic Peptide Dendrimer-Based Drug Delivery System for Cancer Therapy Pharmaceutics amphiphilic peptide dendrimer self-assembling drug delivery cancer therapy |
author_facet |
Dandan Zhu Huanle Zhang Yuanzheng Huang Baoping Lian Chi Ma Lili Han Yu Chen Shengmei Wu Ning Li Wenjie Zhang Xiaoxuan Liu |
author_sort |
Dandan Zhu |
title |
A Self-Assembling Amphiphilic Peptide Dendrimer-Based Drug Delivery System for Cancer Therapy |
title_short |
A Self-Assembling Amphiphilic Peptide Dendrimer-Based Drug Delivery System for Cancer Therapy |
title_full |
A Self-Assembling Amphiphilic Peptide Dendrimer-Based Drug Delivery System for Cancer Therapy |
title_fullStr |
A Self-Assembling Amphiphilic Peptide Dendrimer-Based Drug Delivery System for Cancer Therapy |
title_full_unstemmed |
A Self-Assembling Amphiphilic Peptide Dendrimer-Based Drug Delivery System for Cancer Therapy |
title_sort |
self-assembling amphiphilic peptide dendrimer-based drug delivery system for cancer therapy |
publisher |
MDPI AG |
series |
Pharmaceutics |
issn |
1999-4923 |
publishDate |
2021-07-01 |
description |
Despite being a mainstay of clinical cancer treatment, chemotherapy is limited by its severe side effects and inherent or acquired drug resistance. Nanotechnology-based drug-delivery systems are widely expected to bring new hope for cancer therapy. These systems exploit the ability of nanomaterials to accumulate and deliver anticancer drugs at the tumor site via the enhanced permeability and retention effect. Here, we established a novel drug-delivery nanosystem based on amphiphilic peptide dendrimers (AmPDs) composed of a hydrophobic alkyl chain and a hydrophilic polylysine dendron with different generations (AmPD KK<sub>2</sub> and AmPD KK<sub>2</sub>K<sub>4</sub>). These AmPDs assembled into nanoassemblies for efficient encapsulation of the anti-cancer drug doxorubicin (DOX). The AmPDs/DOX nanoformulations improved the intracellular uptake and accumulation of DOX in drug-resistant breast cancer cells and increased permeation in 3D multicellular tumor spheroids in comparison with free DOX. Thus, they exerted effective anticancer activity while circumventing drug resistance in 2D and 3D breast cancer models. Interestingly, AmPD KK<sub>2</sub> bearing a smaller peptide dendron encapsulated DOX to form more stable nanoparticles than AmPD KK<sub>2</sub>K<sub>4</sub> bearing a larger peptide dendron, resulting in better cellular uptake, penetration, and anti-proliferative activity. This may be because AmPD KK<sub>2</sub> maintains a better balance between hydrophobicity and hydrophilicity to achieve optimal self-assembly, thereby facilitating more stable drug encapsulation and efficient drug release. Together, our study provides a promising perspective on the design of the safe and efficient cancer drug-delivery nanosystems based on the self-assembling amphiphilic peptide dendrimer. |
topic |
amphiphilic peptide dendrimer self-assembling drug delivery cancer therapy |
url |
https://www.mdpi.com/1999-4923/13/7/1092 |
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doaj-d27c1cb2261f4bc2a863e930d12f317a2021-07-23T14:00:53ZengMDPI AGPharmaceutics1999-49232021-07-01131092109210.3390/pharmaceutics13071092A Self-Assembling Amphiphilic Peptide Dendrimer-Based Drug Delivery System for Cancer TherapyDandan Zhu0Huanle Zhang1Yuanzheng Huang2Baoping Lian3Chi Ma4Lili Han5Yu Chen6Shengmei Wu7Ning Li8Wenjie Zhang9Xiaoxuan Liu10State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing 210009, ChinaState Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing 210009, ChinaState Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing 210009, ChinaState Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing 210009, ChinaState Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing 210009, ChinaState Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing 210009, ChinaState Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing 210009, ChinaDepartment of Analytical Chemistry, College of Science, China Pharmaceutical University, Nanjing 210009, ChinaState Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing 210009, ChinaState Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing 210009, ChinaState Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing 210009, ChinaDespite being a mainstay of clinical cancer treatment, chemotherapy is limited by its severe side effects and inherent or acquired drug resistance. Nanotechnology-based drug-delivery systems are widely expected to bring new hope for cancer therapy. These systems exploit the ability of nanomaterials to accumulate and deliver anticancer drugs at the tumor site via the enhanced permeability and retention effect. Here, we established a novel drug-delivery nanosystem based on amphiphilic peptide dendrimers (AmPDs) composed of a hydrophobic alkyl chain and a hydrophilic polylysine dendron with different generations (AmPD KK<sub>2</sub> and AmPD KK<sub>2</sub>K<sub>4</sub>). These AmPDs assembled into nanoassemblies for efficient encapsulation of the anti-cancer drug doxorubicin (DOX). The AmPDs/DOX nanoformulations improved the intracellular uptake and accumulation of DOX in drug-resistant breast cancer cells and increased permeation in 3D multicellular tumor spheroids in comparison with free DOX. Thus, they exerted effective anticancer activity while circumventing drug resistance in 2D and 3D breast cancer models. Interestingly, AmPD KK<sub>2</sub> bearing a smaller peptide dendron encapsulated DOX to form more stable nanoparticles than AmPD KK<sub>2</sub>K<sub>4</sub> bearing a larger peptide dendron, resulting in better cellular uptake, penetration, and anti-proliferative activity. This may be because AmPD KK<sub>2</sub> maintains a better balance between hydrophobicity and hydrophilicity to achieve optimal self-assembly, thereby facilitating more stable drug encapsulation and efficient drug release. Together, our study provides a promising perspective on the design of the safe and efficient cancer drug-delivery nanosystems based on the self-assembling amphiphilic peptide dendrimer.https://www.mdpi.com/1999-4923/13/7/1092amphiphilic peptide dendrimerself-assemblingdrug deliverycancer therapy |