Multi‐Targeting Nano‐Systems Targeting Heterogeneous Cancer Cells for Therapeutics and Biomarker Detection

Abstract

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.

Stromal and tumor immune microenvironment reprogramming through multifunctional cisplatin-based liposomes boosts the efficacy of anti-PD-1 immunotherapy in pancreatic cancer

“…12,37 Currently, nanomedicine-based immunotherapies attempt to target tumor cells, 38,39 cancer mesenchymal fibroblasts, 40 or immune cells. 39,41,42 The immunological activity of multi-targeted nano pharmaceuticals therapy 28,43 is greater than that of single-targeted nanoparticles for tumor cells. 44 ATF@Pt Lps were successfully prepared in our study, and in vitro tumor sphere infiltration and live imaging experiments demonstrated that liposomes modified with ATF peptides enriched drugs in deep tumors, suggesting that the ATF peptide targets mesenchymal tumor and cancer cells and disrupts the stromal barrier, decreasing the expression of α-SMA, collagen I, and fibronectin.…”