Long cruising aptamer-albumin nanobots intelligently capture and restrain circulating tumor cells

Circulating tumor cells (CTC) are the root cause of life-threatening cancer metastases. The rare CTC cannot be specifically killed by anti-cancer agents without producing any side effects, nor be targeted-and-eradicated by antibody or aptamer complexes because of the complexes' limited circulating half-life in the blood owing to metabolism and immune clearance. Here, we build the biosafe and biostable aptamer-albumin nanobots that can cruise in the blood much long together with the CTC, resulting in the increased capture efficiency and specificity of the nanobots targeting CTC. The intelligent-recognizing unit of the novel nanobots is composed of three EpCAM-targeting aptamers (AP) that can specifically target breast CTC, and their sticky ends are completely closed to form the biostable circular trivalent aptamers (CTA). The binding energy, specificity and stability of the circular three arms CTA are significantly superior to their linear AP. After conjugating CTA to human serum albumin (CTA-HSA) by amination reaction, the blood circulation time of CTA-HSA in mice was significantly prolonged by 3 folds, resulting in the enhanced collision probability and increased capture efficiency of CTA-HSA to CTC. CTA-HSA can escape the immune clearance and inhibit adhesion/invasion and cell cycle of CTC, resulting in CTC apoptosis. This proof-of-concept study provides a promising nanobiomaterial for CTC-induced cancer metastases.