University of California, Los Angeles & Cedars-Sinai Medical Center — Thermoresponsive NanoVelcro CTC Purification System for Prostate Cancer Profiling

Project Summary

The long-term objective of this IRCN award is to develop Thermoresponsive (TR)-NanoVelcro circulating tumor cell (CTC) purification system that can be digitally programmed to achieve optimal performance for recovering viable CTCs in prostate cancer (PC) patients' blood, allowing seamless coupling with various downstream molecular assays. The unique mechanism of our devices is that by switching device temperature in a physiologically endurable range (i.e., 4-37 °C), thermoresponsive conformational changes of nanosubstrate-grafted polymer brushes alter the accessibility of capture agent to specifically capture (37 °C) and release (4 °C) CTCs to give viable CTCs in desired purity. Our central hypothesis is that through rational optimization and systematic validation, viable CTCs can be purified for ex vivo expansion, and molecular characterization of freshly isolated and ex vivo expanded CTCs can help better investigate and monitor PC evolution from androgen deprivation therapy (ADT) sensitive states to castration resistant PC (CRPC).

Our major goals are to:

• develop, optimize and validate TR-NanoVelcro CTC purification system,
• demonstrate improved ex vivo expansion of purified CTCs with minimum "expansion bias", and
• establish key genomic and transcriptomic events in PC using both ex vivo expanded and freshly purified CTCs and quantify the potential perturbations introduced by TR-NanoVelcro purification system.

This nanomaterial-embedded cancer diagnostic platform is expected to introduce a unique rare-cell sorting method that enables detection, isolation, and characterization of CTCs in peripheral blood, providing an opportunity to noninvasively monitor the disease progression in individual PC patients. Ultimately, we will broaden the future clinical applications to other types of cancer, and channel TR-NanoVelcro CTC purification system into translational and regulatory pipelines.

Project Expertise

Collectively, the PIs have brought together an interdisciplinary research team with extensive expertise covering nanomaterials, polymer, microfluidics, in vitro diagnostics, urologic oncology, genomic medicine, cancer biology, next-generation sequencing, bioinformatics, and biostatistics to implement the proposed research activities.