Combining hybrid cell membrane modified magnetic nanoparticles and inverted microfluidic chip for in situ CTCs capture and inactivation

Circulating tumor cells (CTCs) serve as crucial indicators for tumor occurrence, progression, and prognosis monitoring. However, achieving high sensitivity and high purity capture of CTCs remains challenging. Additionally, in situ capture and synchronous clearance hold promise as methods to impede tumor metastasis, but further exploration is needed. In this study, biomimetic cell membrane-coated magnetic nanoparticles (NPs) were designed to address the issue of nonspecific adsorption of capture probes by the immune system during blood circulation. Membranes from human breast cancer cells (tumor cell membranes, TMs) and leukocytes (white blood cell membranes, WMs) were extracted and fused to form a hybrid membrane (HM), which was further modified onto the surface of porous magnetic NPs loaded with indocyanine green (ICG). The incorporation of TM enhanced the material's target specificity, thus increasing capture efficiency, while WM coating reduced interference from homologous white blood cells (WBCs), further enhancing capture purity. Additionally, in conjunction with our novel inverted microfluidic chip, this work introduces the first use of polymer photonic crystals as the capture interface for CTCs. Besides providing an advantageous surface structure for CTC attachment, the 808 nm photonic bandgap effectively amplifies the 808 nm excitation light at the capture surface position. Therefore, upon capturing CTCs, the ICG molecules in the probes facilitate enhanced photothermal (PTT) and photodynamic (PDT) synergistic effects, directly inactivating the captured CTCs. This method achieves capture efficiency and purity exceeding 95% and permits in situ inactivation post-capture, providing an important approach for future research on impeding tumor metastasis in vivo.