Inhalable liposomal delivery of osimertinib and DNA for treating primary and metastasis lung cancer
Xianglei Fu1, Yanbin Shi2, Hang Wu3
1NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, PR China.
Abstract:
Lung cancer remains one of the most common malignancies, and its brain metastases significantly worsen the prognosis for patients. Current treatments for lung cancer face many challenges, including poor drug accumulation and the inability to simultaneously control primary and metastatic tumors. Here, we show that the mRNA-binding protein insulin-like growth factor 3 is crucial for non-small cell lung cancer progression and metastasis. We construct an inhalable nanoliposome system to co-deliver osimertinib and DNA plasmid for gene knockdown. Upon inhalation, these nanoparticles efficiently penetrate pulmonary barriers and accumulate in lungs by mimicking natural lung surfactants. Within tumor cells, released osimertinib inhibits tumor growth, while the DNA triggers the production of engineered exosomes that can travel to the brain to suppress tumors. This strategy effectively inhibits both primary and metastatic tumors while enhancing antitumor immune responses. This work suggests that this inhalable nanomedicine offers a safe and versatile strategy for cancer therapy.
Insights
This study presents an inhalable nanomedicine for lung cancer, co-delivering a drug and gene therapy. This dual approach targets primary tumors and brain metastases, offering a novel cancer treatment strategy.
Area of Science:
- Oncology
- Nanomedicine
- Gene Therapy
Background:
- Lung cancer, particularly non-small cell lung cancer (NSCLC), presents significant therapeutic challenges due to poor drug delivery and difficulty in managing both primary and metastatic tumors.
- Metastasis to the brain drastically reduces patient prognosis, highlighting the need for effective treatments targeting disseminated disease.
Purpose of the Study:
- To develop an inhalable nanoliposome system for co-delivery of osimertinib and a DNA plasmid targeting insulin-like growth factor 3 (IGF3) in NSCLC.
- To investigate the efficacy of this dual-delivery system in inhibiting primary lung tumors and brain metastases.
- To evaluate the potential of engineered exosomes derived from the gene therapy to target and suppress metastatic lesions.
Main Methods:
- Construction of inhalable nanoliposomes encapsulating osimertinib and a DNA plasmid for IGF3 gene knockdown.
- Inhalation delivery of nanoparticles to mimic natural lung surfactants for efficient pulmonary penetration and accumulation.
- Assessment of osimertinib's direct tumor inhibition and DNA-induced engineered exosome production for targeting brain metastases.
- Evaluation of combined therapeutic effects on primary and metastatic tumor suppression and antitumor immune responses.
Main Results:
- The inhalable nanoliposomes demonstrated efficient lung penetration and accumulation.
- Co-delivery of osimertinib and DNA plasmid effectively inhibited primary NSCLC tumor growth.
- Engineered exosomes successfully traveled to the brain and suppressed metastatic tumors.
- The nanomedicine strategy enhanced antitumor immune responses and showed efficacy against both primary and metastatic lung cancer.
Conclusions:
- An inhalable nanomedicine system co-delivering osimertinib and a gene knockdown agent offers a promising strategy for treating primary and metastatic lung cancer.
- This dual-action approach, utilizing engineered exosomes for brain metastasis targeting, provides a versatile and potentially safer therapeutic option.
- The findings suggest a novel platform for advanced lung cancer therapy with potential for broader applications.
