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Published on: August 2, 2022
Enhanced Anti-Brain Metastasis from Non-Small Cell Lung Cancer of Osimertinib and Doxorubicin Co-Delivery Targeted
Xiaoqi Wang1, Wenxing Mao2, Zhi Wang3
1Department of Pharmaceutics and Key Laboratory of Cardiovascular & Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing 211166, People's Republic of China.
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.
Insights
A novel T7 peptide-installed nanocarrier (T7-DSNPs/9291) effectively delivers targeted drugs across the blood-brain barrier. This system enhances treatment for non-small cell lung cancer brain metastases, improving survival rates.
Area of Science:
- Oncology
- Nanotechnology
- Pharmacology
Background:
- Treating non-small cell lung cancer (NSCLC) brain metastases is challenging.
- Combining targeted drugs and chemotherapy shows promise but is limited by the blood-brain barrier (BBB).
- Effective drug delivery systems are needed to overcome BBB limitations and enhance synergistic effects.
Purpose of the Study:
- To develop a targeted co-delivery system for NSCLC brain metastases.
- To enhance the synergistic therapeutic effects of targeted drugs and chemotherapy.
- To overcome the limitations imposed by the blood-brain barrier.
Main Methods:
- Developed T7 peptide-installed, drug-loaded nanocarriers (T7-DSNPs/9291).
- Evaluated in vitro efficacy using cell uptake, BBB transport, and MTT assays.
- Assessed in vivo effects using imaging and survival analysis in an animal model.
Main Results:
- T7-DSNPs/9291 significantly enhanced BBB penetration of osimertinib (AZD9291) and doxorubicin.
- Demonstrated enhanced anti-NSCLC brain metastasis effects.
- Prolonged median survival in an intracranial brain metastasis model.
Conclusions:
- T7-DSNPs/9291 is a promising drug delivery system for NSCLC brain metastasis.
- The system enhances drug delivery and therapeutic efficacy.
- Offers potential for combined therapy in treating NSCLC brain metastases.
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