Nanobiotechnology for the capture and manipulation of circulating tumor cells

Abstract

A necessary step in metastasis is the dissemination of malignant cells into the bloodstream, where cancer cells travel throughout the body as circulating tumor cells (CTC) in search of an opportunity to seed a secondary tumor. CTC represent a valuable diagnostic tool: evidence indicates that the quantity of CTC in the blood has been shown to relate to the severity of the illness, and samples are readily obtained through routine blood draws. As such, there has been a push toward developing technologies to reliably detect CTC using a variety of molecular and immunocytochemical techniques. In addition to their use in diagnostics, CTC detection systems that isolate CTC in such a way that the cells remain viable will allow for the performance of live-cell assays to facilitate the development of personalized cancer therapies. Moreover, techniques for the direct manipulation of CTC in circulation have been developed, intending to block metastasis in situ. We review a number of current and emerging micro- and nanobiotechnology approaches for the detection, capture, and manipulation of rare CTC aimed at advancing cancer treatment.

Therapeutic Modulation of Prostate Cancer Metastasis

“…The challenge relates to the fact that CTCs are relatively rare, and their presence is dwarfed by the much greater numbers of blood cells with which they co-circulate. The lone FDA-approved CTC detection platform, CellSearch, uses an antibody to epithelial cell adhesion molecule (EpCAM) to isolate CTCs from blood cells [103,104]. This is then followed by immunostaining, with intact cells positive for cytokeratin and EpCAM and negative for CD45 (a marker of blood cells), deemed to be CTCs.…”

Nanoparticle delivery for metastatic breast cancer

“…Photoacoustic flow cytometry involves the application of pulsed laser light at blood vessels in vivo which can be absorbed by circulating, light absorbing nanoparticles creating localized thermal energy. This can be used for highly sensitive detection of nanoparticle labeled cancer cells using ultrasound or destruction by hyperthermia, depending on the intensity of the incident laser [68]. In 2006, Zharov et al first described the use of photoacoustic flow cytometry to detect gold nanoparticle labeled cancer cells in the circulation of a mouse [64].…”

“…Current limitations of this technology include the lack of robust markers for circulating tumor cells [62] and targeting strategies to enable delivery of targeted nanomaterials specifically to circulating tumor cells [68]. Further, in terms of therapeutics, the shedding of circulating tumor cells is a ongoing process and thus chronic administration of targeted nanomaterials and photothermal ablation might be required to realize clinical benefit [68].…”

“…Further, in terms of therapeutics, the shedding of circulating tumor cells is a ongoing process and thus chronic administration of targeted nanomaterials and photothermal ablation might be required to realize clinical benefit [68].…”

Circulating tumor-cell detection and capture using microfluidic devices

“…Based on these advantages, various microfluidic platforms have been developed for rare-cell capture, including CTCs [15]. Recent progress in microbiotechnology and nanobiotechnology can also aid the development of more advanced CTC-detecting microfluidic devices [16].…”