Enhanced Anti-Brain Metastasis from Non-Small Cell Lung Cancer of Osimertinib and Doxorubicin Co-Delivery Targeted Nanocarrier
Authors Wang X, Mao W, Wang Z, Li X, Xiong Y, Lu H, Wang X, Yin H, Cao X, Xin H
Received 19 April 2020
Accepted for publication 13 July 2020
Published 3 August 2020 Volume 2020:15 Pages 5491—5501
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Mian Wang
Xiaoqi Wang1 ,* Wenxing Mao2 ,* Zhi Wang3 ,* Xinrui Li,1 Yaokun Xiong,4 Hongjin Lu,1 Xiuzhen Wang,1 Haoyuan Yin,1 Xiang Cao,1 Hongliang Xin1
1Department of Pharmaceutics and Key Laboratory of Cardiovascular & Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing 211166, People’s Republic of China; 2Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, People’s Republic of China; 3Department of Pharmacy, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 4School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Hongliang Xin Fax +86 25 86868467; +86 25 86868477
Purpose: Currently, the treatment of brain metastases from non-small cell lung cancer (NSCLC) is rather difficult in the clinic. A combination of small molecule-targeted drug and chemo-drug is a promising therapeutic strategy for the treatment of NSCLC brain metastases. But the efficacy of this combination therapy is not satisfactory due to the blood–brain barrier (BBB). Therefore, it is urgent to develop a drug delivery system to enhance the synergistic therapeutic effects of small molecule–targeted drug and chemo-drug for the treatment of NSCLC brain metastases.
Methods: T7 peptide installed and osimertinib (AZD9291) loaded intracellular glutathione (GSH) responsive doxorubicin prodrug self-assembly nanocarriers (T7-DSNPs/9291) have been developed as a targeted co-delivery system to enhance the combined therapeutic effect on brain metastases from NSCLC. In vitro cell experiments, including intracellular uptake assay, in vitro BBB transportation, and MTT assay were used to demonstrate the efficacy of T7-DSNPs/9291 in NSCLC brain metastasis in vitro. Real-time fluorescence imaging analysis, magnetic resonance imaging analysis, and Kaplan–Meier survival curves were used to study the effect of T7-DSNPs/9291 on an animal model in vivo.
Results: T7-DSNPs/9291 could significantly enhance BBB penetration of AZD9291 and doxorubicin via transferrin receptor-mediated transcytosis. Moreover, T7-DSNPs/9291 showed significant anti-NSCLC brain metastasis effect and prolonged median survival of an intracranial NSCLC brain metastasis animal model.
Conclusion: T7-DSNPs/9291 is a potential drug delivery system for the combined therapy of brain metastasis from NSCLC.
Keywords: drug delivery, brain metastasis, AZD9291, redox-responsive, brain targeted delivery system
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