Excitation Modulation of Upconversion Nanoparticles for Switch-like Control of Ultraviolet Luminescence

The ability to control ultraviolet (UV) luminescence intensity in a switch-like manner is demonstrated through the use of 980 nm excitation pulse-width modulation in NaYF₄:Yb³⁺,Tm³⁺ upconversion nanoparticles (UNPs). Varying the ytterbium doping resulted in a single order of magnitude improvement of UV luminescence intensity. The excitation pulse-width modulation technique applied to these optimized UNPs enables 3 orders of magnitude control over UV luminescence intensity while maintaining NIR luminescence emission at 800 nm. Controlled in the switch-like manner, these UNPs can transfer their UV energy to 9,10-diphenylanthracene (DPA). Independent control of NIR luminescence and UV energy transfer through NIR excitation modulation may find applications in the development of multifunctional theranostic systems

NIR-Activated Content Release from Plasmon Resonant Liposomes for Probing Single-Cell Responses

Technological limitations have prevented the interrogation and manipulation of cellular activity in response to bioactive molecules within model and living systems that is required for the development of diagnostic and treatment modalities for diseases, such as cancer. In this work, we demonstrate that gold-coated liposomes are capable of encapsulation and on-demand release of signaling molecules with a spatial and temporal resolution leading to activation of individual cells. As a model system, we used cells modified to overexpress a certain G-protein coupled receptor, the CCK2 receptor, and achieved its activation in a single cell <i>via</i> the localized release of its agonist. This content release was triggered by illumination of the liposomes at wavelengths corresponding to the plasmon resonance of the gold coating. The use of plasmon resonant liposomes may enable on-demand release of a broad range of molecules using biologically safe near-infrared light and without molecule chemical modification. In combination with the spectral tunability of plasmon resonant coating, this technology may allow for multiplexed interrogation of complex and diverse signaling pathways in model or living tissues with unprecedented spatial and temporal control

Focal Activation of Cells by Plasmon Resonance Assisted Optical Injection of Signaling Molecules

Experimental methods for single cell intracellular delivery are essential for probing cell signaling dynamics within complex cellular networks, such as those making up the tumor microenvironment. Here, we show a quantitative and general method of interrogation of signaling pathways. We applied highly focused near-infrared laser light to optically inject gold-coated liposomes encapsulating bioactive molecules into single cells for focal activation of cell signaling. For this demonstration, we encapsulated either inositol trisphosphate (IP3), an endogenous cell signaling second messenger, or adenophostin A (AdA), a potent analogue of IP, within 100 nm gold-coated liposomes, and injected these gold-coated liposomes and their contents into the cytosol of single ovarian carcinoma cells to initiate calcium (Ca²⁺) release from intracellular stores. Upon optical injection of IP3 or AdA at doses above the activation threshold, we observed increases in cytosolic Ca²⁺ concentration within the injected cell initiating the propagation of a Ca²⁺ wave throughout nearby cells. As confirmed by octanol-induced inhibition, the intercellular Ca²⁺ wave traveled <i>via</i> gap junctions. Optical injection of gold-coated liposomes represents a quantitative method of focal activation of signaling cascades of broad interest in biomedical research