In vivo label-free photoacoustic flow cytography and on-the-spot laser killing of single circulating melanoma cells

Abstract

Metastasis causes as many as 90% of cancer-related deaths, especially for the deadliest skin cancer, melanoma. Since hematogenous dissemination of circulating tumor cells is the major route of metastasis, detection and destruction of circulating tumor cells are vital for impeding metastasis and improving patient prognosis. Exploiting the exquisite intrinsic optical absorption contrast of circulating melanoma cells, we developed dual-wavelength photoacoustic flow cytography coupled with a nanosecond-pulsed melanoma-specific laser therapy mechanism. We have successfully achieved in vivo label-free imaging of rare single circulating melanoma cells in both arteries and veins of mice. Further, the photoacoustic signal from a circulating melanoma cell immediately hardware-triggers a lethal pinpoint laser irradiation to kill it on the spot in a thermally confined manner without causing collateral damage. A pseudo-therapy study including both in vivo and in vitro experiments demonstrated the performance and the potential clinical value of our method, which can facilitate early treatment of metastasis by clearing circulating tumor cells from vasculature.

Label-free high-throughput photoacoustic tomography of suspected circulating melanoma tumor cells in patients in vivo

“…This fragmentation in turn would theoretically lead to the release of melanoma tumor antigens, with subsequent presentation to immune cells, which may help instigate an adaptive immune response. 38,39 This hypothesis is particularly attractive in patients whose metastatic tumors are small or in locations that may not be amenable to other modalities that serve to augment treatment response to immunotherapy, such as radiation or the injection of cytolytic tumor vaccines. LA-PAT can also be applied to image CTCs in the lymph, 40 but the weak optical absorption of lymph may require labeling in order to locate the lymphatic system.…”

Towards Reaching the Total Blood Volume by in vivo Flow Cytometry and Theranostics

“…In particular, in vivo advanced multicolor PA flow cytometry (PAFC) with many innovations (e.g., high pulse rate multispectral lasers, linear beam shape, focused ultrasound transducers, nanobubble‐induced sensitivity amplification, skin pigmentation tolerant signal processing, and cell focusing in blood flow) demonstrated label‐free detection of circulating tumor cells (CTCs) in melanoma patients, malaria‐infected cells, bacteria at bacteremia, and sickled erythrocytes with ~1,000× improved sensitivity and potential to prevent deadly metastasis, sepsis, stroke, and sickle cell crisis by well‐timed treatment, . Moreover, theranostics by integration of PAFC and pulsed photothermal (PT) therapy showed in preclinical studies photomechanical destruction of CTCs, bacteria ( Staphylococcus aureus ), and infected cells directly in blood flow .…”

Fluorescence detection, enumeration and characterization of single circulating cellsin vivo: technology, applications and future prospects

“…al. recently used PA to both enumerate (image) and kill melanoma cells directly in vivo (He et al , 2016). …”