(AGENPARL) – LONDON (UNITED KINGDOM), ven 18 settembre 2020
Circulating tumor cells (CTCs), as a liquid biopsy, have great significance for early diagnosis, timely treatment, and practical evaluation of metastasis or recurrence of cancer. However, the enrichment of rare CTCs in complex blood samples is still a significant challenge. Here, a unique highly-sensitive folic acid (FA)-functionalized cascade amplification system-modified magnetic nanoparticles (MNPs) is constructed for effectively capturing CTCs in whole blood. In this system, numerous FA, as a targeted molecule, were conjugated on the surface of PAMAM dendrimers (PAMAM-FA) (first amplification) through a polyethylene glycol (PEG) linker, which could promote the more comfortable binding of folate receptors (FR) on the surface of ovarian cancer cells (SKOV3 cells). Then, the PAMAM-FA was further modified with biotin to fabricate biotin-PAMAM-FA (BPF), which could combine with streptavidin (SA)-modified MNPs (SMs) via the SA-biotin system for efficiently targeting and separating CTCs. The capture efficiency of the constructed MNPs-SA~biotin-PAMAM-FA (SM@BPF) nanoprobes was 90.3% with high cell viability (~ 93.2%) and minimal non-specific adsorption (~ 25%). Moreover, fewer nanoprobes were absorbed on the surface of SM@BPF-captured SKOV3 cells (one-step method) compared with SM/BPF-captured SKOV3 cells (two-step method), which was beneficial for further biological analysis. We expect such a recognition molecule-based cascade amplification system will provide an innovative CTCs enrichment platform for early-stage diagnosis of ovarian cancer.
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