Cancer signaling by plasmonic quantum probes

Abstract Although the use of gold quantum dots for non-cellular sensing is growing rapidly, the use of quantum gold dots are still limited because of comparatively large overall size (biocompatible layer), overlapped Raman readout of lower concentrated metabolites inside the cells and dispersion of QDs inside the cancer cells. This is due to the labelling of QDs which results in specific binding and non-uniform distribution of QDs inside the cells. Besides this, QDs are toxic in nature due to the presence of chemical residues from the wet synthesis, hampering its rendition to clinical application. To increase biocompatibility and surge the cellular uptake, gold probes are usually layered with bio-films (PEG). However, layering impedes the interaction of metabolites and gold QDs and damp the surface plasmonic resonance, resulting in low Raman signal. The addition of biofilm increases the overall hydrodynamic size of gold QDs, limiting the dispersion and internalization of plasmonic QDs inside the cell as well as the nucleus. Therefore, the unique properties that arise from the quantum size of the plasmonic probe are lost. To retain the quantum size of QDs, there is a need to use a physical method of synthesis and use gold QDs layering free. In this research manuscript, we introduce the quantum sized layering free Plasmonic Quantum Probes (PQPs), a potential tool for cancer sensing which provides the opportunity to attain the sensing of surface oncoprotein, intracellular oncoprotein and nuclear metabolites simultaneously. In this work, we introduce the concept of Plasmonic Quantum Probes (PQPs) for intercellular sensing. To the best of our knowledge, it is the first time the probe close to the size of cellular metabolites was synthesized. By using physical synthesis (multiphoton laser ionization), biocompatible PQPs were synthesized without the chemical adulteration and eliminated the need of biocompatible layering. Since the PQPs are non-toxic in nature, no layering is required, enabling the study of true quantum effect in plasmonic cellular signaling. The naked PQPs demonstrated self-cellular uptake with even dispersion and non-specific attachment to all the cell components. As a result, the Raman spectra revealed rich information of multiple cell components, including surface (e.g., EGFR), intracellular (e.g., HPV E6/HPV E7) and nuclear metabolites (e.g., DNA/RNA), simultaneously in one single Raman profile. Due to the difference in the number of probes inside the cells, the signal strength of cancerous cell is significantly higher than that of fibroblast cells, implying that the differentiation of cancerous cells is possible through the analysis of the intensity of Raman readout. The probe size is found to be inversely related to the signal strength of the plasmonic readout. The PQP provides a holistic picture of cell states and may open up new possibilities for accurate diagnosis of cancer.