Impact of Quantum Dot Surface on Complex Formation with Chlorin e6 and Photodynamic Therapy

Nanomaterials have permeated various fields of scientific research, including that of biomedicine, as alternatives for disease diagnosis and therapy. Among different structures, quantum dots (QDs) have distinctive physico-chemical properties sought after in cancer research and eradication. Within the context of cancer therapy, QDs serve the role of transporters and energy donors to photodynamic therapy (PDT) drugs, extending the applicability and efficiency of classic PDT. In contrast to conventional PDT agents, QDs’ surface can be designed to promote cellular targeting and internalization, while their spectral properties enable better light harvesting and deep-tissue use. Here, we investigate the possibility of complex formation between different amphiphilic coating bearing QDs and photosensitizer chlorin e6 (Ce6). We show that complex formation dynamics are dependent on the type of coating—phospholipids or amphiphilic polymers—as well as on the surface charge of QDs. Förster’s resonant energy transfer occurred in every complex studied, confirming the possibility of indirect Ce6 excitation. Nonetheless, in vitro PDT activity was restricted only to negative charge bearing QD-Ce6 complexes, correlating with better accumulation in cancer cells. Overall, these findings help to better design such and similar complexes, as gained insights can be straightforwardly translated to other types of nanostructures—expanding the palette of possible therapeutic agents for cancer therapy.This article belongs to the Special Issue Nanomaterials for Photothermal/Photodynamic TherapyThe work was supported by the project “Postdoctoral Fellowship Implementation in Lithuania” funded by the European Union Structural Fund and by the project “Programming cells and management of tumor microenvironment for personal therapy in oncology–LASTER” (VP1-3.1-ŠMM-10-V-02-027)

Upconverting nanoparticles as primary thermometers and power sensors

Luminescence thermometry is a spectroscopic technique for remote temperature detection based on the thermal dependence of the luminescence of phosphors, presenting numerous applications ranging from biosciences to engineering. In this work, we use the Er3+ emission of the NaGdF4/NaGdF4:Yb3+,Er3+/NaGdF4 upconverting nanoparticles upon 980 nm laser excitation to determine simultaneously the absolute temperature and the excitation power density. The Er3+ 2H11/2→4 I15/2 and 4 S3/2→4 I15/2 emission bands, which are commonly used for thermometric purposes, overlap with the 2 H9/2 →4 I13/2 emission band, which can lead to erroneous temperature readout. Applying the concept of luminescent primary thermometry to resolve the overlapping Er3+ transitions, a dual nanosensor synchronously measuring the temperature and the delivered laser pump power is successfully realized holding promising applications in laser-supported thermal therapies.publishe

A generalized approach to photon avalanche upconversion in luminescent nanocrystals

Photon avalanching nanoparticles (ANPs) exhibit extremely nonlinear upconverted emission valuable for sub-diffraction imaging, nanoscale sensing, and optical computing. Avalanching has been demonstrated with Tm3+, Nd3+ or Pr3+-doped nanocrystals, but their emission is limited to 600 and 800 nm, restricting applications. Here, we utilize Gd3+-assisted energy migration to tune the emission wavelengths of Tm3+-sensitized ANPs and generate highly nonlinear emission of Eu3+, Tb3+, Ho3+, and Er3+ ions. The upconversion intensities of these spectrally discrete ANPs scale with the nonlinearity factor s = 10-17 under 1064 nm excitation at power densities as low as 6 kW/cm2. This strategy for imprinting avalanche behavior on remote emitters can be extended to fluorophores adjacent to ANPs, as we demonstrate with CdS/CdSe/CdS core/shell/shell quantum dots. ANPs with rationally designed energy transfer networks provide the means to transform conventional linear emitters into a highly nonlinear ones, expanding the use of photon avalanching in biological, chemical, and photonic applications.Comment: 13 pages, 5 figure

Impact of Quantum Dot Surface on Complex Formation with Chlorin e6 and Photodynamic Therapy

Nanomaterials have permeated various fields of scientific research, including that of biomedicine, as alternatives for disease diagnosis and therapy. Among different structures, quantum dots (QDs) have distinctive physico-chemical properties sought after in cancer research and eradication. Within the context of cancer therapy, QDs serve the role of transporters and energy donors to photodynamic therapy (PDT) drugs, extending the applicability and efficiency of classic PDT. In contrast to conventional PDT agents, QDs’ surface can be designed to promote cellular targeting and internalization, while their spectral properties enable better light harvesting and deep-tissue use. Here, we investigate the possibility of complex formation between different amphiphilic coating bearing QDs and photosensitizer chlorin e6 (Ce6). We show that complex formation dynamics are dependent on the type of coating—phospholipids or amphiphilic polymers—as well as on the surface charge of QDs. Förster’s resonant energy transfer occurred in every complex studied, confirming the possibility of indirect Ce6 excitation. Nonetheless, in vitro PDT activity was restricted only to negative charge bearing QD-Ce6 complexes, correlating with better accumulation in cancer cells. Overall, these findings help to better design such and similar complexes, as gained insights can be straightforwardly translated to other types of nanostructures—expanding the palette of possible therapeutic agents for cancer therapy

Phosphorylated paxillin and phosphorylated FAK constitute subregions within focal adhesions

Integrin-mediated adhesions are convergence points for multiple signaling pathways. Their inner structure and diverse functions can be studied with super-resolution microscopy. Here, we examined the spatial organization within focal adhesions by analyzing several adhesion proteins with structured illumination microscopy (SIM). Paxillin (Pax) serves as a scaffold protein and signaling hub in focal adhesions, and focal adhesion kinase (FAK, also known as PTK2) regulates the dynamics of adhesions. We found that their phosphorylated forms, pPax and pFAK, form spot-like, spatially defined clusters within adhesions in several cell lines and confirmed these findings with additional super-resolution techniques. These clusters showed a more regular separation from each other compared with more randomly distributed signals for FAK or paxillin. Mutational analysis indicated that the active (open) FAK conformation is a prerequisite for the pattern formation of pFAK. Live-cell super-resolution imaging revealed that organization in clusters is preserved over time for FAK constructs; however, distance between clusters is dynamic for FAK, while paxillin is more stable. Combined, these data introduce spatial clusters of pPax and pFAK as substructures in adhesions and highlight the relevance of paxillin-FAK binding for establishing a regular substructure in focal adhesions

Double Rare-Earth Nanothermometer in Aqueous Media: Opening the Third Optical Transparency Window to Temperature Sensing

Owing to the alluring possibility of contactless temperature probing with microscopic spatial resolution, photoluminescence nanothermometry at the nanoscale is rapidly advancing towards its successful application in biomedical sciences. The emergence of near-infrared nanothermometers has paved the way for temperature sensing at the deep tissue level. However, water dispersibility, adequate size at the nanoscale, and the capability to efficiently operate in the second and third biological optical transparency windows are requirements that still have to be fulfilled in a single nanoprobe. In this work, these requirements are addressed by rare-earth doped nanoparticles with core/shell-architecture, dispersed in water, whose excitation and emission wavelengths conveniently fall within the biological optical transparency windows. Under the heating-free 800 nm excitation, double nanothermometry is realized either with Ho3+-Nd3+ (1.18-1.34 μm) or Er3+-Nd3+ (1.55-1.34 μm) NIR emission band ratios, both displaying equal thermal sensitivities around 1.1 % ºC-1. It is further demonstrated that, along with the interionic energy transfer processes, the thermometric properties of these nanoparticles are also governed by the temperature dependent energy transfer to the surrounding solvent (water) molecules. Overall, this work presents a novel water dispersible double ratiometric nanothermometer operating in the second and third biological optical transparency windows. The temperature dependent particle-solvent interaction is also presented, which is critical for e.g. future in vivo applications

Spectral characterization of LiYbF₄ upconverting nanoparticles

In this work, rare-earth-based nanoparticles based on LiYbF4 and doped with Er3+, Tm3+ and Ho3+ were investigated. The effect of the concentration of the dopant ions was thoroughly studied from a spectroscopic standpoint under 980 nm excitation. The upconversion emission that originates from the absorption of the optical energy from the Yb3+ ions in the crystal lattice and the subsequent energy transfer to the other rare earth in the lattice (i.e., Er3+, Tm3+ or Ho3+) highly depends on the concentration of the latter ion. Overall, the findings in this manuscripts provide important insights into the properties and rational design of upconverting nanoparticles

Inert shell effect on the quantum yield of neodymium-doped near-Infrared nanoparticles: the necessary shield in an aqueous dispersion

Lanthanide-doped nanoparticles (LnNPs) are versatile near-infrared (NIR) emitting nanoprobes that have led to their growing interest for use in biomedicine-related imaging. Toward the brightest LnNPs, high photoluminescence quantum yield (PLQY) values are attained by implementing core/shell engineering, particularly with an optically inert shell. In this work, a thorough investigation is performed to quantify how an outer inert shell maintains the PLQY of Nd3+-doped LnNPs dispersed in an aqueous environment. Three relevant quantitative findings affecting the PLQY of Nd3+-doped LnNPs are identified: (i) the PLQY of core LnNPs is improved 3-fold upon inert shell coating; (ii) PLQY decreases with increasing Nd3+ doping despite the inert shell; and (iii) solvent quenching has a major influence on the PLQY of the LnNPs, though it is relatively lessened for high Nd3+ doping. Overall, we shed new light on the impact of the LnNP architecture on the NIR emission, as well as on the quenching effects caused by doping concentration and solvent molecules.publishe

Near infrared bioimaging and biosensing with semiconductor and rare-earth nanoparticles: recent developments in multifunctional nanomaterials.

Research in novel materials has been extremely active over the past few decades, wherein a major area of interest has been nanoparticles with special optical properties. These structures can overcome some of the intrinsic limitations of contrast agents routinely used in medical practice, while offering additional functionalities. Materials that absorb or scatter near infrared light, to which biological tissues are partially transparent, have attracted significant attention and demonstrated their potential in preclinical research. In this review, we provide an at-a-glance overview of the most recent developments in near infrared nanoparticles that could have far-reaching applications in the life sciences. We focus on materials that offer additional functionalities besides diagnosis based on optical contrast: multiple imaging modalities (multimodal imaging), sensing of physical and chemical cues (multivariate diagnosis), or therapeutic activity (theranostics). Besides presenting relevant case studies for each class of optically active materials, we discuss their design and safety considerations, detailing the potential hurdles that may complicate their clinical translation. While multifunctional nanomaterials have shown promise in preclinical research, the field is still in its infancy; there is plenty of room to maximize its impact in preclinical studies as well as to deliver it to the clinics