Upconversion Nanoparticles Research Articles

Effect of Surface Modification on the Luminescence of Individual Upconversion Nanoparticles.

Lanthanide-doped upconversion nanoparticles (UCNPs) hold promise for single-molecule imaging owing to their excellent photostability and minimal autofluorescence. However, their limited water dispersibility, often from the hydrophobic oleic acid ligand during synthesis, is a challenge. To address this, various surface modification strategies' impact on single-particle upconversion luminescence are studied. UCNPs are made hydrophilic through methods like ligand exchange with dye IR806, HCl or NOBF4 treatment, silica coating (SiO2 or mesoporous mSiO2), and self-assembly with polymer of DSPE-PEG or F127. The studies revealed that UCNPs modified with NOBF4 and DSPE-PEG exhibited notably higher single-particle brightness with minimal quenching (3% and 8%, respectively), followed by SiO2, F127, IR806, mSiO2, and HCl (84% quenching). HCl disrupted UCNPs's crystal lattice, weakening luminescence, while mSiO2 absorbed solvent molecules, causing luminescence quenching. Energy transfer to IR806 also reduced the brightness. Additionally, a prevalence of upconversion red emission over green is observed, with the red-to-green ratio increasing with irradiance. UCNPs coated with DSPE-PEG exhibited the brightest single-particle luminescence in water, retaining 48% of its original emission due to a lower critical micelle concentration and superior water protection. In summary, the investigation provides valuable insights into the role of surface chemistry on UCNPs at the single-particle level.

Enhancement of enzyme activity by laser-induced energy propulsion of upconverting nanoparticles under near-infrared light: A comprehensive methodology for in vitro and in vivo applications

If the appropriate immobilization method and carrier support are not selected, partial decreases in the activity of enzymes may occur after immobilization. Herein, to overcome this challenge, an excitation mechanism that enables energy transfer was proposed. Modified upconverting nanoparticles (UCNPs) were constructed and the important role of near-infrared (NIR) excitation in enhancing the catalytic activity of the enzyme was demonstrated. For this purpose, UCNPs were first synthesized via the hydrothermal method, functionalized with isocyanate groups, and then, PEG-L-ASNase was immobilized via covalent binding. UCNPs with and without PEG-L-ASNase were extensively characterized by different methods. These supports had immobilization yield and activity efficiency of >96 % and 78 %, respectively. Moreover, immobilized enzymes exhibited improved pH, thermal, and storage stability. In addition, they retained >65 % of their initial activity even after 20 catalytic cycles. Biochemical and histological findings did not indicate a trend of toxicity in rats due to UCNPs. Most importantly, PEG-L-ASNase activity was triggered approximately 5- and 2-fold under in vitro and in vivo conditions, respectively. Overall, it is anticipated that this pioneering work will shed new light on the realistic and promising usage of NIR-excited UCNPs for the immobilization of enzymes in expensive and extensive applications.

Upconversion 3D Bioprinting for Noninvasive In Vivo Molding.

Tissue engineered bracket materials provide essential support for the physiological protection and therapeutics of patients. Unfortunately, the implantation process of such devices poses the risk of surgical complications and infection. In this study, an upconversion nanoparticles (UCNPs)-assisted 3D bioprinting approach is developed to realize in vivo molding that is free from invasive surgery. Reasonably designed UCNPs, which convert near-infrared (NIR) photons that penetrate skin tissues into blue-violet emission (300-500 nm), induce a monomer polymerization curing procedure in vivo. Using a fused deposition modeling coordination framework, a precisely predetermined trajectory of the NIR laser enables the manufacture of implantable medical devices with tailored shapes. A proof of the 3D bioprinting of a noninvasive fracture fixation scaffold is achieved successfully, thus demonstrating an entirely new method of in vivo molding for biomedical treatment.

Silk‐Based Functional Inks with Color‐Tunable Light Upconversion for Printing on Arbitrary Surfaces

AbstractA biocompatible and versatile silk‐based functional ink with hydrophilic upconversion nanoparticles (UCNPs) that can be printed or painted on arbitrary substrates, including biological surfaces is demonstrated. Hydrophilic UCNPs, ready to be dispersed in aqueous silk fibroin solution, are synthesized in large quantities via facile hydrothermal synthesis using citric acid. Based on a systematic study of dopant control to achieve robust red emission from citrate‐capped UCNPs, three primary colors are obtained, which serve as the basis for the expansion of the color palette. The synthesized UCNPs are homogeneously dispersed in regenerated silk fibroin solutions derived from Bombyx mori cocoons to produce water‐based functional inks. Cyan, magenta, and yellow (CMY) inks are created by combining red, green, and blue (RGB) inks. Demonstrator devices, where a variety of colorful patterns and codes are revealed only under near‐infrared irradiation, are realized through stencil printing or brush painting on flexible polymer films, fruit, leaves, silkworm cocoons, and pig skin. The patterns and codes are highly heat resistant (≈230 °C) and can be easily washed off with water after use. The printable/paintable inks and functions proposed here will provide new opportunities for applications where sustainability, biocompatibility, and intentional luminescence are simultaneously required.

DNA‐Programmed (De)Hybridization of Near‐Infrared Photosensitized UCNP‐QDs‐GNPs Nanoprobes for MicroRNA Imaging and Image‐Guided Cancer Therapy

AbstractAccurate and sensitive analysis of cancer‐associated microRNAs in living tissue is of great significance for the early diagnosis and treatment of cancer. Herein, a hierarchical nanoprobe denoted as UCNP‐QDs‐GNPs is delicately designed, where a near‐infrared (NIR) absorptive upconversion nanoparticle (UCNP) serves as the core, broad‐absorptive and bright emissive quantum dots (QDs) and emission‐quencher gold nanoparticles (GNPs) surround as satellites for microRNA imaging and image‐guided cancer therapy. Through the programmed assembly of heterobivalent DNA‐conjugated QDs with DNA‐modified GNPs and UCNPs, the well‐defined nanostructured UCNP‐QDs‐GNPs are generated with quenched fluorescence. Upon encountering the microRNA‐21 target, GNPs underwent catalytic disassembly, resulting in the concurrent recovery and amplification of fluorescence from QDs and UCNPs, which enabled sensitive imaging and quantification of microRNA‐21 within living cells. Furthermore, dithiol‐constituted aggregation‐induced emission (AIE) photosensitizers bonded on the surface of QDs, are effectively photosensitized by the QDs. The NIR excitation harvested by UCNPs is therefore efficiently transferred to QDs and subsequently converged on the AIE photosensitizers, boosting photodynamic activity for image‐guided therapy in deep‐seated tumors. The DNA‐programmed (de)hybridization strategy, facilitating the conversion of NIR excitation into imaging signals and photodynamic activity, offers a promising avenue for the early theranostics of malignancies.

PEG-coated NaYF4:Tm3+/Yb3+ upconversion nanoparticles for OCT image contrast enhancer, optical thermometry, and security applications

Polyethylene glycol (PEG) coated NaYF4:Tm3+/Yb3+ upconversion nanoparticles (UCNPs) were synthesized, and their usefulness in improving image contrast in Swept source optical coherence tomography (SS-OCT) and photo-thermal (PT-OCT) imaging was assessed. Synthesized UCNPs have shown biocompatibility with a cell survival rate of more than 90% after 24 h of incubation of HeLa cells. Prepared particles have shown intense blue upconversion emission along with a photo-thermal conversion efficiency of 30.4%. Leveraging these UCNPs, enhancements in image quality were achieved in both SS-OCT and PT-OCT imaging modalities, manifesting improved scattering coefficients and contrast-to-noise ratios. Temperature-dependent upconversion emission spectra were used to assess temperature sensing and thermal sensitivity of 107×10-3 K-1 at 300 K is obtained for the synthesized nanoparticles. Additionally, these UCNPs have demonstrated utility in latent finger-marks detection and anti-counterfeiting applications.

Gum Arabic-stabilized upconverting nanoparticles for printing applications

Upconverting nanoparticles (UCNPs) have been proposed for a variety of applications ranging from biomedical probes to luminescent sensors and security tags. Yet, bringing UCNPs into real-life, technologically relevant products requires implementation into industry-friendly processes. The need for stable dispersions, clean films or dry powders challenges users who look for a way to use UCNPs. In this work, an ink formulation was developed that offers a straightforward way to print UCNPs on glass and metallic substrates. The use of Gum Arabic as biocompatible emulsifier allowed to implement the NaGdF4:Er,Yb/NaGdF4 core/shell UCNPs into water-based ink formulations without the need of complex surface chemistry. The formulation, based on water, glycerin, and propanediol, exhibited good stability and applicability for printing with a commercial aerosol jet printer. Bright upconversion emission was retained upon printing, and the obtained UCNP films were used in proof-of-concept luminescent thermal sensing.

DNA conformational change embrace ultraviolet photolysis: A dual-mode sensing platform for electrochemical and fluorescent signaling

We developed a dual-mode biosensor that utilizes DNA conformational changes and ultraviolet photolysis for electrochemical (EC) and fluorescence (FL) detection. In this study, a stem-loop-structured carcinoembryonic antigen (CEA) aptamer was modified on an Au electrode, and this aptamer contained a redox-labeled methylene blue (MB), short-chain DNA with a 6-carboxylic fluorescein (FAM) and a PC linker that can be cleaved by ultraviolet light. Subsequently, CEA and CEA antibody-modified upconversion nanoparticle bioconjugates (CEA-Ab@UCNPs) were added. In the presence of CEA, Ab@UCNPs can bind CEA and push the MB which was originally close to the electrode surface, away from the electrode surface, resulting in a reduced redox current. Under irradiation with a 980 nm laser, the UCNPs emit ultraviolet light, leading to photocleavage of the PC linker and the release of FAM for FL sensing. Under optimal conditions, the EC and FL modes showed good responses to CEA within 0.01–50 ng/mL and 0.1–80 ng/mL, respectively.

A magnetic-enhanced FRET biosensor for simultaneous detection of multiple antibodies

Accurate, rapid and sensitive detection of specific immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies in human samples is crucial for preventing and assessing pandemics, especially in the case of recent COVID-19 outbreaks. However, simultaneous and efficient detection of IgG and IgM in a single system remains challenging. Herein, we developed a multicolor nanosystem capable of quantitatively analyzing anti-SARS-CoV-2 IgG and IgM with high sensitivity within 20 ​min. The detection system consists of core-shell upconversion nanoparticles (csUCNPs), secondary antibodies labeled with fluorescent dyes (sab), and magnetic nanocrystals (PMF). By leveraging the Förster resonance energy transfer (FRET) effect, the photoluminescence (PL) intensity of blue and green regions is restored for IgG and IgM detection, respectively. Inspiringly, owing to the introducing of PMF, the limits of detection (LODs) of IgG and IgM tested are improved to 89 ​fmol ​L−1 and 19.4 ​fmol ​L−1, representing about 416-folds and 487-folds improvement over only-dye dependent system, respectively. Mechanistic investigations reveal that the high collective effect and surface energy transfer efficiency from csUCNPs to PMF contribute to the enhanced detection sensitivity. The assay enables us to quantify clinical vaccinated samples with high specificity and precision, suggesting our multicolor platform can be a promising alternative for clinical point-of-care serological assay.

Fluorescent aptasensor for highly sensitive detection of Staphylococcus aureus based on dual-amplification strategy by integrating DNA walking and hybridization chain reaction

Food-borne diseases caused by bacteria threaten human health. Herein, we presented a new fluorescent aptasensor by coupling DNA walking and hybridization chain reaction (HCR) for convenient and sensitive quantification of bacteria. Staphylococcus aureus (S. aureus) was selected as target. When there was target in the system, the binding of S. aureus with its aptamer caused the disintegration of aptamer/DNA walker on the surface of AuNPs and released DNA walker. With the help of Nt.BsmAI, DNA walker moved along the surface of AuNPs and trigger probe was detached from AuNPs. The trigger probe could initiate hybridization chain reaction (HCR) and opened the stems of H1@AuNPs probe and H2@AuNPs probe. After the addition of nicking endonuclease, the adjacent upconversion nanoparticles (UCNPs, NaYF4:Yb3+, Er3+) were further away from the quenchers (AuNPs) of H1 and H2. Therefore, the fluorescence intensity of UCNPs could be restored via fluorescence resonance energy transfer (FRET). Bacteria were thus detected by recording the fluorescence intensity of UCNPs. This method is simple, rapid and sensitive. It can directly detect bacteria in a low background signal. The limit of detection (LOD) was 10 CFU/mL, detection time was less than 3 h. Recovery rates in simulated milk, honey and human serum samples ranged from 93.6 % to 105.8 %. The strategy opens up new paths for early diagnosis of diseases and food monitoring.

Hydrogen‐bonded organic framework core–shell composite for synergistic antimicrobial therapy

AbstractHydrogen‐bonded organic frameworks (HOFs) are crystalline porous materials with permanent voids formed via self‐assembly of organic molecules through hydrogen bonding and intermolecular forces. Further combination of HOFs with functional material would broaden their application horizon but were less explored in existing literature. Herein, a highly porous and photosensitive HOF was successfully coated onto upconversion nanoparticles (UCNPs) to construct a core–shell structure named UNCPs@PFC‐73‐Ni. To enhance spectral overlap and maximize energy conversion efficiency, this study utilized the Er and Tm co‐doped UCNPs, which can effectively convert infrared light into visible light emission thereby exciting the porphyrin shell. Subsequent investigation reveals that the composite exhibits significant photodynamic and photothermal effects under infrared light. Encouraged by its noticeable photoactivity, UCNPs@PFC‐73‐Ni was evaluated as an antibacterial agent against Escherichia coli. Notably, significant antibacterial efficacy was observed, highlighting the potential of UCNPs@PFC‐73‐Ni as an effective antibacterial agent under infrared light irradiation.

Upconverting-photon quenching-mediated perforation influx as an intracellular delivery method using posAuNP@UCNPs nanocomposites for osteoarthritis treatment

Photoporation techniques based on plasmonic nanoparticles such as gold nanoparticles have been extensively studied for the intracellular delivery of substances via cell membrane disruption. However, the clinical application of AuNP is challenging due to its absorption in the 500 nm region of the light spectrum. To overcome this challenge, upconversion nanoparticles were employed to stimulate AuNP at NIR wavelengths. posAuNP@UCNPs nanocomposites were produced by coating 30 nm UCNPs on 80 nm AuNPs using DOPA-PEI, which were then irradiated with 980 nm NIR light to facilitate their intracellular delivery. TEM and DLS confirmed that posAuNP and UCNP combine to form nanocomposites. Additionally, multiphysics simulation was used to analyze the distribution of the posAuNP electric field based on morphological differences that change as the UCNP ratio increases. Next, effective LED irradiation conditions were established by applying upconverting-photon quenching-mediated perforation influx to C28/I2 cells as suspensions or spheroids. posAuNP@UCNP nanocomposites were confirmed to be effective for the delivery of baricitinib as a treatment for osteoarthritis in a three-dimensional osteoarthritis model. Finally, chondrocyte differentiation was induced through intracellular delivery of baricitinib using posAuNP@UCNPs. The findings suggest that posAuNP@UCNPs have great potential as a tool for non-invasive drug delivery via UCPPin.Graphical

Silica-coated LiYF4:Yb3+, Tm3+ upconverting nanoparticles are non-toxic and activate minor stress responses in mammalian cells.

Lanthanide-doped upconverting nanoparticles (UCNPs) are ideal candidates for use in biomedicine. The interaction of nanomaterials with biological systems determines whether they are suitable for use in living cells. In-depth knowledge of the nano-bio interactions is therefore a pre-requisite for the development of biomedical applications. The current study evaluates fundamental aspects of the NP-cell interface for square bipyramidal UCNPs containing a LiYF4:Yb3+, Tm3+ core and two different silica surface coatings. Given their importance for mammalian physiology, fibroblast and renal proximal tubule epithelial cells were selected as cellular model systems. We have assessed the toxicity of the UCNPs and measured their impact on the homeostasis of living non-malignant cells. Rigorous analyses were conducted to identify possible toxic and sub-lethal effects of the UCNPs. To this end, we examined biomarkers that reveal if UCNPs induce cell killing or stress. Quantitative measurements demonstrate that short-term exposure to the UCNPs had no profound effects on cell viability, cell size or morphology. Indicators of oxidative, endoplasmic reticulum, or nucleolar stress, and the production of molecular chaperones varied with the surface modification of the UCNPs and the cell type analyzed. These differences emphasize the importance of evaluating cells of diverse origin that are relevant to the intended use of the nanomaterials. Taken together, we established that short-term, our square bipyramidal UCNPs are not toxic to non-malignant fibroblast and proximal renal epithelial cells. Compared with established inducers of cellular stress, these UCNPs have minor effects on cellular homeostasis. Our results build the foundation to explore square bipyramidal UCNPs for future in vivo applications.

Near-infrared-driven upconversion nanoparticles with photocatalysts through water-splitting towards cancer treatment.

Water splitting is promising, especially for energy and environmental applications; however, there are limited studies on the link between water splitting and cancer treatment. Upconversion nanoparticles (UCNPs) can be used to convert near-infrared (NIR) light to ultraviolet (UV) or visible (Vis) light and have great potential for biomedical applications because of their profound penetration ability, theranostic approaches, low self-fluorescence background, reduced damage to biological tissue, and low toxicity. UCNPs with photocatalytic materials can enhance the photocatalytic activities that generate a shorter wavelength to increase the tissue penetration depth in the biological microenvironment under NIR light irradiation. Moreover, UCNPs with a photosensitizer can absorb NIR light and convert it into UV/vis light and emit upconverted photons, which excite the photoinitiator to create H2, O2, and/or OH˙ via water splitting processes when exposed to NIR irradiation. Therefore, combining UCNPs with intensified photocatalytic and photoinitiator materials may be a promising therapeutic approach for cancer treatment. This review provides a novel strategy for explaining the principles and mechanisms of UCNPs and NIR-driven UCNPs with photocatalytic materials through water splitting to achieve therapeutic outcomes for clinical applications. Moreover, the challenges and future perspectives of UCNP-based photocatalytic materials for water splitting for cancer treatment are discussed in this review.

NIR-Triggered Release of Nitric Oxide by Upconversion-Based Nanoplatforms to Enhance Osteogenic Differentiation of Mesenchymal Stem Cells for Osteoporosis Therapy.

Stem cell therapy is an attractive approach to bone tissue regeneration in osteoporosis (OP); however, poor cell engraftment and survival within injured tissues limits its success in clinical settings. Nitric oxide (NO) is an important signaling molecule involved in various physiological processes, with emerging evidence supporting its diverse roles in modulating stem cell behavior, including survival, migration, and osteogenic differentiation. To control and enhance osteogenic differentiation of mesenchymal stem cells (MSCs) for OP therapy, we designed a near-infrared (NIR) light-triggered NO-releasing nanoplatform based on upconversion nanoparticles (UCNPs) that converts 808-nm NIR light into visible light, stimulating NO release by light control. We demonstrate that the UCNP nanoplatforms can encapsulate a light-sensitive NO precursor, Roussin's black salt (RBS), through the implementation of a surface mesoporous silica coating. Upon exposure to 808-nm irradiation, NO is triggered by the controlled upconversion of UCNP visible light at the desired time and location. This controlled release mechanism facilitates photoregulated differentiation of MSCs toward osteogenic lineage and avoids thermal effects and phototoxicity on cells, thus offering potential therapeutic applications for treating OP invivo. Following the induction of osteogenic differentiation, the UCNP nanoplatforms exhibit the capability to serve as nanoprobes for the real-time detection of differentiation through enzymatic digestion and fluorescence recovery of UCNPs, enabling assessment of the therapeutic efficacy of OP treatment. Consequently, these UCNP-based nanoplatforms present a novel approach to control and enhance osteogenic differentiation of MSCs for OP therapy, simultaneously detecting osteogenic differentiation for evaluating treatment effectiveness.

Effect of Yb3+ concentration on the upconversion emission properties of sub 10 nm RbY2F7:Yb, Er nanoparticles.

Upconversion nanoparticles (UCNPs) are a fascinating group of luminescent materials known for their ability to convert low-energy photons to high-energy photons. Many inorganic UCNPs have been studied to understand the underlying mechanism of upconversion phenomena, out of which alkali rare-earth fluorides (AREFs) such as NaREF4, LiREF4 and KREF4 were found to exhibit high upconversion efficiencies. This work investigates a similar AREF upconversion nanoparticle viz RbY2F7:Yb, Er. This UCNP system was synthesised by a modified thermal decomposition method by varying the Yb concentration from 20% to 98%. Structural analysis using XRD revealed that all the synthesised samples were found to be formed in the orthorhombic phase irrespective of the increasing Yb concentration. The thermal decomposition method greatly aided in the reduction of particle size. HRTEM analysis revealed that the as-synthesised UCNPs have a spherical morphology with an average particle size of 7.9 ± 0.2 nm. The upconversion emission studies taken by exciting the samples with a 975 nm laser show three distinct peaks at 527, 542 and 656 nm. The experimental results indicate that the increased Yb3+ concentration improves the red to green intensity ratio by supporting the 4F9/2 → 4I15/2 transition of Er3+ through the energy back transfer process between Er3+ and Yb3+. Notably, there is a reduction in the overall emission intensity with increasing Yb3+ concentration. Furthermore, the decay lifetime studies show a decreasing trend at 542 nm and 656 nm emission lines with an increase in the Yb concentration, which is because of the concentration quenching effect of the increasing Yb concentration.

Upconversion circularly polarized luminescence of cholesteric liquid crystal polymer networks with NaYF4:Yb,Tm UCNPs.

Upconversion circularly polarized luminescence (UC-CPL) exhibits promising potential for application for anti-counterfeiting and displays. Upconversion nanoparticles (UCNPs), NaYF4:Yb,Tm, with uniform morphology and high crystallinity, were prepared via a simple solvothermal method. These UCNPs were embedded into cholesteric liquid crystal polymer network (CLCN) films. The UC-CPL performance of these films was investigated using left- and right-handed circular polarizers. After calibration, the |gcallum| values (up to 0.33) were obtained for the free-standing CLCN-UCNPs films, while a |gcallum| value of 0.43 was achieved for the CLCN-UCNPs-coated PET film. Moreover, a combined system comprising a PMMA-UCNPs layer and a CLCN layer yielded an ultra-large |gcallum| value of up to 1.73. Flexible and colourful patterned CLCN films were fabricated using photomasks, offering potential applications in anti-counterfeiting. This study not only successfully prepared UC-CPL-active materials based on CLCNs and UCNPs, but also demonstrated the chiral filtering effect of CLCN films in upconversion luminescent materials.

A scalable fabrication method for gold nanodisk-upconverting nanoparticle hybrid nanostructures.

Plasmonic nanostructures can be used to enhance the efficiency of upconversion nanoparticles (UCNPs) and enable new functionalities. However, the fabrication of these hybrid plasmon-UCNP nanostructures has traditionally relied on either wet chemistry or nanolithography routes that are difficult to control, scale up, or both. In this work, we present a scalable nanofabrication process, capable of producing a massive array of gold-UCNP hybrid nanostructures over a few mm2 area and with excellent uniformity in the photoluminescence intensity. This new approach combines the scalability of the bottom-up self-assembly method and the precision of the top-down nanolithography approach. It provides an efficient alternative route for the production of plasmonically enhanced UCNPs. A detailed discussion on the optimization of the UCNP self-assembly, the gold nanodisk lithography, and the nanopattern transfer processes is presented here. Additionally, we showcase the potential of this new approach for fabricating mechanical force sensors based on the selective plasmonic enhancement of the UCNP emission. This new approach holds great potential in facilitating the production of plasmonically enhanced UCNPs that can be deployed for both imaging and sensing applications.

Thermal properties of nanofluids using hydrophilic and hydrophobic LiYF4:Yb/Er upconverting nanoparticles.

Luminescent nanoparticles have shown great potential for thermal sensing in bio-applications. Nonetheless, these materials lack water dispersibility that can be overcome by modifying their surface properties with water dispersible molecules such as cysteine. Herein, we employ LiYF4:Er3+/Yb3+ upconverting nanoparticles (UCNPs) capped with oleate or modified with cysteine dispersed in cyclohexane or in water, respectively, as thermal probes. Upconversion emission was used to sense temperature with a relative thermal sensitivity of ∼1.24% K-1 (at 300 K) and a temperature uncertainty of 0.8 K for the oleate capped and of 0.5 K for cysteine modified NPs. To study the effect of the cysteine modification in the heat transfer processes, the thermal conductivity of the nanofluids was determined, yielding 0.123(6) W m-1 K-1 for the oleate capped UCNPs dispersed in cyclohexane and 0.50(7) W m-1 K-1 for the cysteine modified UCNPs dispersed in water. Moreover, through the heating curves, the nanofluids' thermal resistances were estimated, showing that the cysteine modification partially prevents heat transfer.

Photodynamic therapy using hybrid nanoparticles comprising of upconversion nanoparticles and chlorin e6-bearing pullulan.

With its minimal invasiveness, photodynamic therapy (PDT) is considered one of the most elegant modalities in cancer treatment. In this study, a facile hybrid nanoparticle was developed, composed of upconversion nanoparticles and chlorin e6-bearing pullulan, which can serve as a photosensitizer activated by a near-infrared red laser. Cell death induction in cancer cells was achieved through energy transfer from the near-infrared red laser emitted by the upconversion nanoparticles to chlorin e6. The therapeutic efficacy of our hybrid system surpassed that of the clinically available photosensitizer, Photofrin, and hybrid liposomes comprising upconversion nanoparticles and chlorin e6 were employed as control. Accumulation of our system in tumor tissue in tumor xenograft mice was primarily achieved through the enhanced permeability and retention (EPR) effect. The administered hybrids were excreted from each organ within 21 days after administration, minimizing the risk of undesirable side effects. Notably, our system exhibited 400 times higher PDT activity in tumor-bearing mice compared to the control groups. It also effectively inhibited metastasis.