Reprogramming the navigation of quantum probes in cancer initiating cells - Unlocking the pathway for next generation nanomedicine

Nanomedicine possesses the immense potential to tackle cancer effectively. Cancer recurrence is predominantly due to this small subpopulation of cells with stem cell properties known as Cancer stem cells (CSCs). Studies have established a clear understanding of nanomaterial`s uptake mechanism in cancer cells; however, the internalization pathway in cancer stem cells remains unclear. Given the scarcity and importance of CSCs, it is critical to emphasize the focus on the uptake of nanoparticles in CSC, which will pave the way for next-generation CSC nanomedicine. To the best of our knowledge, this study is the first to reveal the complex uptake mechanism of nanoparticles in CSC comprehensively. We successfully introduced the mechanism of nanomaterial uptake in preclinical models of CSCs derived from lung cancer and pancreatic cancer, which account for most cancer deaths. Tailoring the Quantum probes with favorable surface functional groups is a practical approach to predetermine the intracellular destination. We successfully programmed the uptake pathway by tuning the surface functional groups on the Quantum probes, enabling us to effectively direct the probes to distinct subcellular locations to perform specific functions. In this study, we achieved the Quantum probes` synthesis and surface functionalization by adopting a non-chemical approach using ultrashort laser pulses. We synthesized sub-10 nm Quantum probes and decorated them with favorable surface functional groups by manipulating the laser plume`s ionic components. The Quantum probes enriched with specific functional groups determine their lysosomal escape and localization, which decides the potential applications such as diagnostic, therapeutic, and theranostics. In addition to the surface functionalization, maintaining the probe size down to 2 nm has provided additional functionality to increase the efficiency of delivering nanomedicine to the CSC. Our results have also shown that the quantum probes do not interfere with the cellular dynamics and are highly biocompatible, eliminating a dedicated biocompatible coating. These results present a whole new perception of the fundamental processes involved in the internalization of nanoparticles into the CSCs through a regulated pathway and subcellular fate for specific applications that could unlock a new frontier in the next generation of broad-spectrum CSC nanomedicine.