A Self-Assembling Amphiphilic Peptide Dendrimer-Based Drug Delivery System for Cancer Therapy

被引:24
|
作者
Zhu, Dandan [1 ,2 ]
Zhang, Huanle [1 ,2 ]
Huang, Yuanzheng [1 ,2 ]
Lian, Baoping [1 ,2 ]
Ma, Chi [1 ,2 ]
Han, Lili [1 ,2 ]
Chen, Yu [1 ,2 ]
Wu, Shengmei [3 ]
Li, Ning [1 ,2 ,4 ]
Zhang, Wenjie [1 ,2 ]
Liu, Xiaoxuan [1 ,2 ]
机构
[1] China Pharmaceut Univ, Ctr Adv Pharmaceut & Biomat, State Key Lab Nat Med, Nanjing 210009, Peoples R China
[2] China Pharmaceut Univ, Ctr Adv Pharmaceut & Biomat, Jiangsu Key Lab Drug Discovery Metab Dis, Nanjing 210009, Peoples R China
[3] China Pharmaceut Univ, Dept Analyt Chem, Coll Sci, Nanjing 210009, Peoples R China
[4] Fujian Med Univ, Sch Pharm, Fuzhou 350122, Peoples R China
基金
中国国家自然科学基金;
关键词
amphiphilic peptide dendrimer; self-assembling; drug delivery; cancer therapy; BIOMEDICAL APPLICATIONS; NANOTECHNOLOGY; RESISTANCE; SIRNA; PH;
D O I
10.3390/pharmaceutics13071092
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 KK2 and AmPD KK2K4). 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 KK2 bearing a smaller peptide dendron encapsulated DOX to form more stable nanoparticles than AmPD KK2K4 bearing a larger peptide dendron, resulting in better cellular uptake, penetration, and anti-proliferative activity. This may be because AmPD KK2 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.
引用
收藏
页数:11
相关论文
共 50 条
  • [41] Adaptive Amphiphilic Dendrimer-Based Nanoassemblies as Robust and Versatile siRNA Delivery Systems
    Liu, Xiaoxuan
    Zhou, Jiehua
    Yu, Tianzhu
    Chen, Chao
    Cheng, Qiang
    Sengupta, Kheya
    Huang, Yuanyu
    Li, Haitang
    Liu, Cheng
    Wang, Yang
    Posocco, Paola
    Wang, Menghua
    Cui, Qi
    Giorgio, Suzanne
    Fermeglia, Maurizio
    Qu, Fanqi
    Pricl, Sabrina
    Shi, Yanhong
    Liang, Zicai
    Rocchi, Palma
    Rossi, John J.
    Peng, Ling
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2014, 53 (44) : 11822 - 11827
  • [42] Biomimetic self-assembling polymeric nanosystems for drug delivery
    Salvage, J. P.
    Hanlon, G. W.
    Lloyd, A. W.
    Ma, I. Y.
    Armes, S. P.
    Billingham, N. C.
    Lewis, A. L.
    JOURNAL OF PHARMACY AND PHARMACOLOGY, 2004, 56 : S104 - S104
  • [43] Self-Assembling Tacrolimus Nanomicelles for Retinal Drug Delivery
    Gote, Vrinda
    Mandal, Abhirup
    Alshamrani, Meshal
    Pal, Dhananjay
    PHARMACEUTICS, 2020, 12 (11) : 1 - 31
  • [44] Self-assembling galactosyl cyclodextrins for targeted drug delivery
    Kan, E
    Darcy, R
    13TH EUROPEAN SYMPOSIUM ON ORGANIC CHEMISTRY, 2003, : 37 - 41
  • [45] Self-assembling asymmetric peptide-dendrimer micelles - a platform for effective and versatile in vitro nucleic acid delivery
    Kokil, Ganesh R.
    Veedu, Rakesh N.
    Le, Bao Tri
    Ramm, Grant A.
    Parekh, Harendra S.
    SCIENTIFIC REPORTS, 2018, 8
  • [46] Self-assembling asymmetric peptide-dendrimer micelles – a platform for effective and versatile in vitro nucleic acid delivery
    Ganesh R. Kokil
    Rakesh N. Veedu
    Bao Tri Le
    Grant A. Ramm
    Harendra S. Parekh
    Scientific Reports, 8
  • [47] pH-triggered morphological change in a self-assembling amphiphilic peptide used as an antitumor drug carrier
    Gong, Zhongying
    Liu, Xiaoying
    Wu, Jingliang
    Li, Xiaocheng
    Tang, Ziqian
    Deng, Yating
    Sun, Xiumei
    Chen, Kun
    Gao, Zhiqin
    Bai, Jingkun
    NANOTECHNOLOGY, 2020, 31 (16)
  • [48] Sustained ocular drug delivery utilizing dendrimer-based hydrogels
    不详
    NANOMEDICINE, 2012, 7 (12) : 1800 - 1800
  • [49] BIOMATERIALS BASED ON SELF-ASSEMBLING α,β-PEPTIDE MOTIFS
    Nagarkar, R.
    Schneider, J.
    BIOPOLYMERS, 2009, 92 (04) : 317 - 317
  • [50] Self-Assembling Peptide-Based Nanoarchitectonics
    Zhao, Luyang
    Zou, Qianli
    Yan, Xuehai
    BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, 2019, 92 (01) : 70 - 79