Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, Hubei, 430072, China.
School of Life Sciences, Anhui Medical University, Hefei, Anhui, 230011, China.
Adv Sci (Weinh). 2023 Oct;10(29):e2303309. doi: 10.1002/advs.202303309. Epub 2023 Aug 17.
Cell fusion plays a critical role in cancer progression and metastasis. However, effective modulation of the cell fusion behavior and timely evaluation on the cell fusion to provide accurate information for personalized therapy are facing challenges. Here, it demonstrates that the cancer cell fusion behavior can be efficiently modulated and precisely detected through employing a multifunctional delivery vector to realize cancer targeting delivery of a genome editing plasmid and a molecular beacon-based AND logic gate. The multifunctional delivery vector decorated by AS1411 conjugated hyaluronic acid and NLS-GE11 peptide conjugated hyaluronic acid can specifically target circulating malignant cells (CMCs) of cancer patients to deliver the genome editing plasmid for epidermal growth factor receptor (EGFR) knockout. The cell fusion between CMCs and endothelial cells can be detected by the AND logic gate delivered by the multifunctional vector. After EGFR knockout, the edited CMCs exhibit dramatically inhibited cell fusion capability, while unedited CMCs can easily fuse with human umbilical vein endothelial cells (HUVEC) to form hybrid cells. This study provides a new therapeutic strategy for preventing cancer progression and a reliable tool for evaluating cancer cell fusion for precise personalized therapy.
细胞融合在癌症的进展和转移中起着关键作用。然而，有效地调节细胞融合行为，并及时评估细胞融合，为个性化治疗提供准确的信息，这方面面临着挑战。在这里，通过使用多功能递送载体来实现基因编辑质粒和基于分子信标的与门逻辑的癌症靶向递送来高效地调节和精确地检测癌细胞融合行为。由与 AS1411 缀合的透明质酸和 NLS-GE11 肽缀合的透明质酸修饰的多功能递送载体可以特异性地靶向癌症患者的循环恶性细胞 (CMC)，以递送用于表皮生长因子受体 (EGFR) 敲除的基因编辑质粒。多功能载体递送的与门逻辑可以检测 CMC 与内皮细胞之间的细胞融合。在 EGFR 敲除后，编辑后的 CMC 表现出明显抑制细胞融合的能力，而未编辑的 CMC 则可以轻易地与人脐静脉内皮细胞 (HUVEC) 融合形成杂交细胞。这项研究为预防癌症进展提供了一种新的治疗策略，并为评估癌症细胞融合以实现精确的个性化治疗提供了一种可靠的工具。
