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Cancer heterogeneity plays a vital part in cancer resistance and metastasis. To provide a reliable approach to exert a therapy action and evaluate its efficiency in heterogeneous cancer cells, a multiple targeting delivery vector composed of histone encapsulating the therapeutic or diagnostic agent, hyaluronic acid targeting CD44 overexpressed in stem tumor cells, SYL3C aptamer targeting epithelial cell adhesion molecule (EpCAM) overexpressed in epithelial cancer cells, and CL4 aptamer targeting epidermal growth factor receptor (EGFR) overexpressed in mesenchymal cancer cells, is developed. The vector can efficiently target different cancer cells and circulating tumor cells (CTCs) in the peripheral blood of patients for mucin 1 (MUC1) knockout. Furthermore, the multiple targeting vector can be used to co‐encapsulate three types of molecular beacons for probing various mRNA biomarkers at single‐cell resolution after genome editing. This study provides an efficient approach for exerting therapeutic actions in heterogeneous cancer cells and assessing the therapeutic efficacy by detection of cancer biomarkers via liquid biopsy.
A multiple targeting delivery vector targeting epithelial, mesenchymal, and stem cancer cells can efficiently deliver therapeutic and diagnostic agents to circulating tumor cells in peripheral blood. This study provides an effective approach to exert a therapy action and evaluate its efficiency in heterogeneous cancer cells by detection of cancer biomarkers via blood biopsy.