Enhanced Anti-Brain Metastasis from Non-Small Cell Lung Cancer of Osimertinib and Doxorubicin Co-Delivery Targeted Nanocarrier

• Published in: International journal of nanomedicine Vol. 15; pp. 5491 - 5501
• Main Authors: Wang, Xiaoqi, Mao, Wenxing, Wang, Zhi, Li, Xinrui, Xiong, Yaokun, Lu, Hongjin, Wang, Xiuzhen, Yin, Haoyuan, Cao, Xiang, Xin, Hongliang
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2020; Dove
• Subjects: Acrylamides - administration & dosage; Aniline Compounds - administration & dosage; Animals; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Blood-Brain Barrier - drug effects; Brain Neoplasms - drug therapy; Brain Neoplasms - mortality; Brain Neoplasms - secondary; Cancer metastasis; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Chemotherapy; Collagen Type IV - chemistry; Doxorubicin - administration & dosage; Drug Carriers - administration & dosage; Drug Carriers - chemistry; Drug delivery systems; Drug Delivery Systems - methods; Health aspects; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Male; Mice, Inbred BALB C; Nanostructures - administration & dosage; Nanostructures - chemistry; Non-small cell lung cancer; Original Research; Osimertinib; Peptide Fragments - chemistry; Prodrugs - administration & dosage; Prodrugs - chemistry; Receptors, Transferrin - metabolism; Small cell lung cancer; Xenograft Model Antitumor Assays; China; brain metastasis; brain targeted delivery system; redox-responsive; drug delivery; AZD9291
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S258699

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. 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. 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. T7-DSNPs/9291 is a potential drug delivery system for the combined therapy of brain metastasis from NSCLC.