Research
How to Design Targeted Nanoparticles to Deliver Drugs to Specific Cells as Efficiently as Coronavirus Delivering RNA to ACE2-Overexpressing Cells?
SARS-CoV-2 can efficiently target and bind to cells expressing ACE2 (receptors) in the respiratory system through its small size (100-140 nm) and the multiple copies of spike protein trimmers (ligands). Despite that SARS-CoV-2 brought us a big disaster, this smart coronavirus’s strategies to deliver genomic materials to ACE2-expressing cells inspire us to design drug delivery systems for different diseases by leveraging nanotechnology and active targeting.
We aim to design nanoparticles modified with optimal peptide targeting ligands to deliver drugs or vaccines to specific cells and organs.
How to Fill the Gap of Lacking Technology to Monitor Metastatic Tumor Dormancy (An Arrest in Tumor Growth) and Lacking Dormancy-Driven Drugs?
Cancer patients may achieve tumor dormancy and long-term survival after primary therapy or develop distant metastasis months or years later and succumb to cancer. Metastasis is responsible for about 90% of cancer deaths. However, we are currently short of dormancy-driven drugs for administration post primary therapy. We also urgently need new imaging technology capable of detecting metastasis earlier than CT scanning that can only detect macro-metastases (> 2 mm tumor nodes). These new imaging technologies are expected to detect micro-metastases (0.2-2 mm tumor nodes) or sense immune signals preparing for the growth of metastatic tumors.
We aim to (1) develop an immune-directed imaging method to sense immune alteration before metastatic outgrowth in the major organs, and (2) design immunotherapeutic drugs that can restore immune surveillance in the major organs after tumor resection surgery.
How to Better Understand Metastasis to the Lungs and Respiratory Infections With A Newly-Developed Lung-Mimicking In Vivo Model?
The longitudinal study of lung diseases is challenging due to the limitation of technology to analyze the lung environment without sacrificing the animals. In vitro or in vivo three-dimensional models mimicking the lung environment can facilitate lung study. We recently created a lung-mimicking in vivo model with microporous scaffold implants, which can develop similar immune signals to the lungs and recruit lung-tropic tumor cells from the circulation in the breast cancer setting. This newly-developed lung-mimicking model revealed the mechanism underlying immune regulation of metastatic dormancy (arrest of tumor growth) and metastatic outgrowth (uncontrollable tumor growth) of breast cancer in the lungs.
We are employing this lung-mimicking in vivo model to study different lung diseases (cancer, infections, allergy), aiming to find new therapeutic targets.
Images were created with BioRender.com.