A paclitaxel and microRNA-124 coloaded stepped cleavable nanosystem against triple negative breast cancer

Autor: Chuanrong Chen, Yourong Duan, Hongze Liao, Hao Fu, Ming Shen, Qianqian Guo, Jian Yu
Rok vydání: 2020
Předmět:
Synergistic antitumour effect
lcsh:Medical technology
Paclitaxel
MicroRNA-124
lcsh:Biotechnology
Biomedical Engineering
Pharmaceutical Science
Medicine (miscellaneous)
Mice
Nude
Bioengineering
Apoptosis
Triple Negative Breast Neoplasms
Applied Microbiology and Biotechnology
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Cell Movement
lcsh:TP248.13-248.65
Cell Line
Tumor
Hyaluronic acid
PEG ratio
Tumor Microenvironment
Animals
Triple negative breast cancer
Hyaluronic Acid
Receptor
Triple-negative breast cancer
030304 developmental biology
Stepped cleavable nanoparticles
0303 health sciences
Tumor microenvironment
Mice
Inbred BALB C
biology
Chemistry
Research
CD44
Molecular medicine
MicroRNAs
Hyaluronan Receptors
lcsh:R855-855.5
030220 oncology & carcinogenesis
biology.protein
Cancer research
Molecular Medicine
Female
Zdroj: Journal of Nanobiotechnology
Journal of Nanobiotechnology, Vol 19, Iss 1, Pp 1-17 (2021)
ISSN: 1477-3155
Popis: Background Triple negative breast cancer (TNBC) is one of the most biologically aggressive breast cancers and lacks effective treatment options, resulting in a poor prognosis. Therefore, studies aiming to explore new therapeutic strategies for advanced TNBC are urgently needed. According to recent studies, microRNA-124 (miR124) not only inhibits tumour growth but also increases the sensitivity of TNBC to paclitaxel (PTX), suggesting that a platform combining PTX and miR124 may be an advanced solution for TNBC. Results Herein, we constructed a stepped cleavable calcium phosphate composite lipid nanosystem (CaP/LNS) to codeliver PTX and miR124 (PTX/miR124-NP). PTX/miR124-NP exhibited superior tumor microenvironment responsive ability, in which the surface PEG layer was shed in the mildly acidic environment of tumor tissues and exposed oligomeric hyaluronic acid (o-HA) facilitated the cellular uptake of CaP/LNS by targeting the CD44 receptor on the surface of tumor cells. Inside tumour cells, o-HA detached from CaP/LNS due to the reduction of disulfide bonds by glutathione (GSH) and inhibited tumour metastasis. Then, PTX and miR124 were sequentially released from CaP/LNS and exerted synergistic antitumour effects by reversing the Epithelial-Mesenchymal Transition (EMT) process in MDA-MB-231 cells. Moreover, PTX/miR124-NP showed significant antitumour efficiency and excellent safety in mice bearing MDA-MB-231 tumours. Conclusion Based on these results, the codelivery of PTX and miR124 by the CaP/LNS nanosystem might be a promising therapeutic strategy for TNBC.
Databáze: OpenAIRE
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