Integration of 3D Fluorescence Imaging and Luminescent Thermometry with Core-Shell Engineered NaYF4:Nd3+/Yb3+/Ho3+ Nanoparticles.

The design of rare-earth-doped upconversion/downshifting nanoparticles (NPs) for theoretical use in nanomedicine has garnered considerable interest. Previous research has emphasized luminescent nanothermometry and photothermal therapy, while three-dimensional (3D) near-infrared (NIR) luminescent tracers have received less attention. Our study introduces Nd3+-, Yb3+-, and Ho3+-doped NaYF4 core-shell luminescent NPs as potential multiparametric nanothermometers and NIR imaging tracers. Nd3+ sensitizes at 804 nm, while Yb3+ bridges to activators Ho3+. We evaluated the photoluminescence properties of Nd3+-, Yb3+-, and Ho3+-doped core and core-shell NPs synthesized via polyol-mediated and thermal decomposition methods. The NaYF4:NdYbHo(7/15/3%)@NaYF4:Nd(15%) core-shell NPs demonstrate competitive nanothermometry capabilities. Specifically, the polyol-synthesized sample exhibits a sensitivity of 0.27% K-1 at 313 K (40 °C), whereas the thermally decomposed synthesized sample shows a significantly higher sensitivity of 0.55% K-1 at 313 K (40 °C) in the near-infrared range. Control samples indicate back energy transfer processes from both Yb and Ho to Nd, while Yb to Ho energy transfer enhances Ho3+-driven upconversion transitions in green and red wavelengths, suggesting promise for photodynamic therapy. Fluorescence molecular tomography confirms 3D NIR fluorescence nanoparticle localization in a biological media after injection, highlighting the potential of core-shell NPs as NIR luminescent tracers. The strategy's clinical impact lies in photothermal treatment planning, leveraging core-shell NPs for (pre)clinical applications, and enabling the easy addition of new functionalities through distinct ion doping.

Surface-Doped Zinc Gallate Colloidal Nanoparticles Exhibit pH-Dependent Radioluminescence with Enhancement in Acidic Media.

As abnormal acidic pH symbolizes dysfunctions of cells, it is highly desirable to develop pH-sensitive luminescent materials for diagnosing disease and imaging-guided therapy using high-energy radiation. Herein, we explored near-infrared-emitting Cr-doped zinc gallate ZnGa2O4 nanoparticles (NPs) in colloidal solutions with different pH levels under X-ray excitation. Ultrasmall NPs were synthesized via a facile hydrothermal method by controlling the addition of ammonium hydroxide precursor and reaction time, and structural characterization revealed Cr dopants on the surface of NPs. The synthesized NPs exhibited different photoluminescence and radioluminescence mechanisms, confirming the surface distribution of activators. It was observed that the colloidal NPs emit pH-dependent radioluminescence in a linear relationship, and the enhancement reached 4.6-fold when pH = 4 compared with the colloidal NPs in the neutral solution. This observation provides a strategy for developing new biomaterials by engineering activators on the nanoparticle surfaces for potential pH-sensitive imaging and imaging-guided therapy using high-energy radiation.

What NIR photodynamic activation offers molecular targeted nanomedicines: Perspectives into the conundrum of tumor specificity and selectivity.

Near infrared (NIR) photodynamic activation is playing increasingly critical roles in cutting-edge anti-cancer nanomedicines, which include spatiotemporal control over induction of therapy, photodynamic priming, and phototriggered immunotherapy. Molecular targeted photonanomedicines (mt-PNMs) are tumor-specific nanoscale drug delivery systems, which capitalize on the unparalleled spatio-temporal precision of NIR photodynamic activation to augment the accuracy of tumor tissue treatment. mt-PNMs are emerging as a paradigm approach for the targeted treatment of solid tumors, yet remain highly complex and multifaceted. While ligand targeted nanomedicines in general suffer from interdependent challenges in biophysics, surface chemistry and nanotechnology, mt-PNMs provide distinct opportunities to synergistically potentiate the effects of ligand targeting. This review provides what we believe to be a much-need demarcation between the processes involved in tumor specificity (biomolecular recognition events) and tumor selectivity (preferential tumor accumulation) of ligand targeted nanomedicines, such as mt-PNMs, and elaborate on what NIR photodynamic activation has to offer. We discuss the interplay between both tumor specificity and tumor selectivity and the degree to which both may play central roles in cutting-edge NIR photoactivable nanotechnologies. A special emphasis is made on NIR photoactivable biomimetic nanotechnologies that capitalize on both specificity and selectivity phenomena to augment the safety and efficacy of photodynamic anti-tumor regimens.

Membrane composition is a functional determinant of NIR-activable liposomes in orthotopic head and neck cancer.

Near-infrared (NIR)-activable liposomes containing photosensitizer (PS)-lipid conjugates are emerging as tunable, high-payload, and tumor-selective platforms for photodynamic therapy (PDT)-based theranostics. To date, the impact that the membrane composition of a NIR-activable liposome (the chemical nature and subsequent conformation of PS-lipid conjugates) has on their in vitro and in vivo functionality has not been fully investigated. While their chemical nature is critical, the resultant physical conformation dictates their interactions with the immediate biological environments. Here, we evaluate NIR-activable liposomes containing lipid conjugates of the clinically-used PSs benzoporphyrin derivative (BPD; hydrophobic, membrane-inserting conformation) or IRDye 700DX (hydrophilic, membrane-protruding conformation) and demonstrate that membrane composition is critical for their function as tumor-selective PDT-based platforms. The PS-lipid conformations were primarily dictated by the varying solubilities of the two PSs and assisted by their lipid conjugation sites. Conformation was further validated by photophysical analysis and computational predictions of PS membrane partitioning (topological polar surface area [tPSA], calculated octanol/water partition [cLogP], and apparent biomembrane permeability coefficient [Papp]). Results show that the membrane-protruding lipo-IRDye700DX exhibits 5-fold more efficient photodynamic generation of reactive molecular species (RMS), 12-fold expedited phototriggered burst release of entrap-ped agents, and 15-fold brighter fluorescence intensity as compared to the membrane-inserting lipo-BPD-PC (phosphatidylcholine conjugate). Although the membrane-inserting lipo-BPD-PC exhibits less efficient photo-dynamic generation of RMS, it allows for more sustained phototriggered release, 10-fold greater FaDu cancer cell phototoxicity, and 7.16-fold higher tumor-selective delivery in orthotopic mouse FaDu head and neck tumors. These critical insights pave the path for the rational design of emerging NIR-activable liposomes, whereby functional consequences of membrane composition can be tailored toward a specific therapeutic purpose.

Efficient multicolor tunability of ultrasmall ternary-doped LaF3 nanoparticles: energy conversion and magnetic behavior.

Luminescence-tunable multicolored LaF3:xCe3+,xGd3+,yEu3+ (x = 5; y = 1, 5, 10, and 15 mol%) nanoparticles have been synthesized via a low cost polyol method. Powder X-ray diffraction and high-resolution transmission electron microscopy studies confirm the hexagonal phase of the LaF3:xCe3+,xGd3+,yEu3+ nanophosphors with average sizes (oval shape) ranging from 5 to 7 nm. Energy-dispersive X-ray spectroscopy analyses show the uniform distribution of Ce3+, Gd3+, and Eu3+ dopants in the LaF3 host matrix. The photoluminescence spectra and electron paramagnetic resonance measurements guarantee the presence of Eu2+, corroborated through DC susceptibility measurements of the samples displaying paramagnetic behavior at 300 K, whereas weak ferromagnetic ordering is shown at 2 K. The non-radiative energy transfer processes from the 4f(2F5/2) → 5d state (Ce3+) to the intraconfigurational 4f excited levels of rare earth ions and simultaneous emissions in the visible region from the 4f65d1 (Eu2+) and 5D0 (Eu3+) emitting levels, leading to overlapped broad and narrow emission bands, have been proclaimed. The energy transfer mechanism proposes involvement of the Gd3+ ion sub-lattice as the bridge and finally trapping by Eu2+/3+, upon excitation of the Ce3+ ion. The calculation of experimental intensity parameters (Ω2,4) has been discussed and the highest emission quantum efficiency (η = 85%) of the Eu3+ ion for the y = 10 mol% sample is reported. The advantageous existence of the Eu2+/Eu3+ ratio along with variously doped nanomaterials described in this work, results in tunable emission color in the blue-white-red regions, highlighting the potential application of the samples in solid-state lighting devices, scintillation devices, and multiplex detection.