Research Projects

1.1. Rationale of the Research Metastasis is the leading cause of cancer mortality, driven largely by rare tumor subpopulations like circulating tumor cells (CTCs) and dormant disseminated tumor cells (DTCs). These cells adapt to harsh tumor microenvironments (TME) hypoxia, acidosis, nutrient deprivation via plastic transcriptional responses. Existing models often fail to replicate these stress gradients or validate rare cell phenotypes in vivo. A translational gap persists in understanding how stress alters cancer cell identity. Integrating biomimetic microfluidics, smart nanocarriers, and single-cell transcriptomics offers a promising approach to reveal conserved mechanisms behind early metastasis. This proposal employs a dual-platform strategy to study the stress-adaptive profiles of rare cancer cells. 1.2. Scientific Objectives The goal is to create an experimental system combining microfluidics, aptamer-functionalized fluorescent mesoporous silica nanoparticles (fMSNs), and single-cell RNA sequencing to profile rare cells under stress. Specific aims include building a microfluidic chip mimicking key tumor stresses and engineering fMSNs targeting epithelial and mesenchymal markers to isolate rare cells both in vitro and in vivo (xenograft models). Isolated cells will be analysed for transcriptional changes linked to metastasis and plasticity. 1.3. Hypothesis/Model We hypothesize that rare cancer cells show conserved stress-induced transcriptomic changes across biomimetic and in vivo settings, notably in EMT, stemness, metabolism, and immune evasion. These can be detected via aptamer-guided fMSNs and single-cell RNA-seq, offering biomarkers of metastasis-initiating cells. 1.4. Main Experiments Microfluidic chips and aptamer-coupled fMSNs (~100 nm) will be developed. Stress conditions will be applied to breast and pancreatic cancer cells in vitro. Rare cells will be captured and sequenced. In vivo, luciferase-tagged MDA-MB-231 xenografts in mice will allow fMSN-guided isolation of cells from blood and organs. Single-cell data will undergo trajectory and pathway analysis. 1.5. Significance This work may define stress-induced molecular fingerprints of metastatic cells, enhance tumor-on-chip relevance, and inform early diagnostics via liquid biopsy. The hybrid platform could enable targeted drug testing and personalized cancer treatment