Upconverting nanoparticles, which transform low-energy infrared radiation into high-energy visible or UV light, show great potential in today's technology. High-quality upconversion colloid (UCC) consisting of lanthanide-based nanoparticles with a diameter of ~10 nm was obtained using a combination of two processes: high-temperature coprecipitation and hydrothermal treatment in an autoclave. The UCC was then PEGylated with PEG-alendronate (PEG-Ale) to facilitate its dispersion in aqueous cell culture media intended for in vitro cell uptake assays. The surface modification of the nanoparticles increased both the colloidal stability in water and the upconversion emission by mitigating surface quenching. UCC@Ale-PEG was characterized by transmission and scanning electron microscopy, dynamic light scattering, and fluorescence microscopy detecting upconversion photoluminescence emission. The results of an in vitro assay revealed that this new generation of UCC can be internalized by various cell types, including epithelial cells and macrophages, upon several hours of exposure, suggesting broad application potential of this type of UCC in biomedicine, bioengineering, and environmental sciences.

Poly(N,N-dimethylacrylamide-co-2-aminoethyl acrylate)-coated core-shell NaYF4:Yb3+,Er3+@NaYF4:Nd3+ upconverting nanoparticles (UCNPs) functionalized with cyanine dye and hypericin were developed as a dual-purpose nanocarriers for simultaneous photodynamic therapy (PDT) and bioimaging of SKBR3 breast cancer cells. The nanoparticles efficiently transported photosensitizers into cells, enabling spatiotemporal control of intracellular Localisation and photoactivation. Confocal and fluorescence lifetime imaging analyses confirmed nanoparticle uptake, distribution, and Förster resonance energy transfer between the cyanine dye and hypericin. Upon near-infrared irradiation, the system induced a light-driven switch between autophagy and apoptosis, validated by biochemical and imaging assays. Western blot and caspase-3 activation demonstrated pathway-specific responses depending on the formulation and irradiation conditions. Moreover, the proposed surface-engineered particles possess the potential for enhanced lymphatic targeting. This study highlights the capacity of multifunctional UCNP-based nanoplatforms to mediate controlled therapeutic responses and improve selectivity in breast cancer treatment.

Upconverting nanoparticles (UCNPs) have attracted much attention in nanomedicine due to their ability to upconvert photons. However, their adverse effects hinder the biomedical applications. In this paper, bisphosphonate-modified poly(isobutylene-alt-maleic acid)-graft-poly(N,N-dimethylacrylamide)-coated NaYF4:Yb,Er,Pr UCNPs (UCNP@PIMAPDMA) nanoparticles were designed, which exhibited luminescence emission simultaneously in the visible and NIR-II regions. The developed UCNPs were characterized by a range of physicochemical methods, including transmission electron and energy dispersive microscopy (TEM and EDAX), dynamic light scattering (DLS), X-ray diffraction analysis (XRD), spectrofluorometry, X-ray photoelectron spectroscopy (XPS), and so forth. The UCNP@PIMAPDMA nanoparticles were also evaluated in cell cultures and experimental animals. The particles showed good biocompatibility with cultured human embryonic kidney HEK293 cells commonly used in toxicological studies. Neat UCNPs were cytotoxic towards these cells, which was confirmed by measuring their viability using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. Blood serum proteins adhered to the surface of UCNP@PIMAPDMA particles, forming a protein corona that may contribute to particle biosafety. After intravenous injection of these particles into laboratory mice, there were no statistically significant changes in body mass of the treated animals. Also, no big adverse effects on blood cell profile, enzymatic and metabolic markers of hepatotoxicity and nephrotoxicity were observed. Finally, the application potential of UCNP@PIMAPDMA nanoparticles was confirmed by successfully imaging the cytoplasm of rat mesenchymal stem cells and rat C6 glioblastoma cells using laser scanning confocal microscopy.

Combining luminescence with magnetic resonance imaging (MRI) is a noninvasive approach that significantly improves detection sensitivity and diagnostic precision for severe diseases. In diabetes care, this approach considerably broadens the possibilities for monitoring of Langerhans islet transplantation by improving their detectability and quantification within existing imaging modalities, including MRI. To realize this concept, upconverting nanoparticles (UCNPs) appear particularly promising, providing bimodal MRI and luminescence with the ability of near-infrared (NIR) light to penetrate deep into tissues. In this work, novel monodisperse dumbbell-shaped core-shell UCNPs (CS-UCNPs) coated with poly(methyl vinyl ether-alt-maleic acid) (PMVEMA) are developed for the bimodal imaging of Langerhans islets. Codoping of Fe, Yb, and Er ions in the NaYF4 host matrix, along with the presence of NaGdF4:Nd, Yb, Tb shell, increases both r 1 and r 2 relaxivities and upconversion luminescence in the red region, which is suitable for in vivo applications. The biocompatible PMVEMA coating ensures colloidal stability of the particles in aqueous physiological fluids and their nontoxicity. The potential of CS-UCNPs for simultaneous MRI and optical visualization is tested on isolated Langerhans islets. The efficiency of in vivo visualization of CS-UCNP@PMVEMA-labeled Langerhans islets transplanted under the kidney capsule in a rat model is investigated using T 1-, T 2-, and T 2*-weighted MRI sequences.

Factors affecting the drug release from biodegradable microparticles are reviewed. It is shown that spherical microparticles ranging in diameters from below 1μ to over 100μ along with the nanoparticles with the size less than 1000nm are particularly effective. The role of molecular weight, molecular weight distribution and co-polymer ratio and distribution is also discussed. Important drug parameters are the solubility of the drug in biological fluids and possible polymer particle-drug interactions. The role of microporosity may be essential in delivery of high molecular weight substances.

Biomaterials are a key element of bone tissue engineering, where they can act as scaffolds for tissue regeneration. The goal of presented research is to evaluate the influence of oleic acid (OA) on the structure and properties of poly(ɛ-caprolactone), or PCL, (with molar masses: 45  000 and 80  000 g/mol), hydroxyapatite (HAp) composites and to determine the optimal OA to HAp ratio ensuring optimal material properties. Visual assessment as well as light and scanning electron microscopy revealed improved dispersion of HAp in the PCL matrix due to its amphiphilic character and, therefore, stabilisation of HAp by OA. However, excessive OA caused deterioration of the PCL45k membrane as cracks were observed. Moreover, the mechanical performance also decreased when the OA to HAp ratio was greater than 1:3 (by weight). Raman spectra confirmed that such effects were due to the increasing amorphous nature of the membranes with increasing OA concentration. Two-dimensional correlation spectroscopy (2D-COS) revealed clear differences in the response of the PCL-HAp system to increasing OA content depending on the molar mass of PCL. Considering the obtained data, the OA:HAp ratio in the PCL matrix ensuring a homogeneous structure and the highest mechanical performance is 1:6 by weight.

Scaffolds are an important part of tissue engineering strategies to support bone regeneration. In particular, composite materials show great potential, but achieving strong interphase coherence is difficult when components with very different physicochemical properties are combined. In this study, we produced multicomponent composites of poly(ε-caprolactone) (PCL), micro- and nano-hydroxyapatite (HA), iron oxide magnetic nanoparticles (MNPs), and oleic acid (OA), which plays a crucial role as a surfactant in enhancing material homogeneity. TEM images showed improved dispersion of OA-stabilized MNPs with a size of about 15 nm. OA presence on the MNPs surface was confirmed by TGA and spectroscopic analyses. Produced composites with OA formed morphologically uniform membranes with good macro-scale dispersion of HA and MNPs, in contrast to those without OA. SEM-EDX and TEM images confirmed the spherulitic morphology of the PCL matrix and also showed improved dispersion of HA in the presence of OA. TGA analysis showed that the size of the HA particle (-nano/-micro) affected its interactions with both the MNPs and the PCL matrix. Moreover, Raman spectroscopy indicated that PCL crystallinity was strongly influenced by MNPs incorporation and less affected by HA.

Photodynamic therapy (PDT) is a highly selective, clinically approved, minimally invasive technique that effectively eliminates cancer cells. Its effectiveness is limited by poor light penetration into tissue and the hydrophobic nature of photosensitizers, highlighting the need for new approaches to treatment. Here, a theranostic upconversion nanoplatform, consisting of a NaYF4:Yb,Er,Tm,Fe core and a NaHoF4 shell codoped with Yb, Nd, Gd and Tb ions, was designed to enhance PDT outcomes by integrating multi-wavelength upconversion luminescence, T2-weighted magnetic resonance imaging (MRI) and PDT. The synthesized core–shell upconversion nanoparticles (CS-UCNPs) were coated with new verteporfin (VP)-conjugated alendronate-terminated poly(N,N-dimethylacrylamide-co-2-aminoethyl acrylate) [Ale-P(DMA-AEA)] grafted with poly(ethylene glycol) (PEG). Under 980 nm NIR irradiation, CS-UCNP@Ale-P(DMA-AEA)-PEG-VP nanoparticles generated reactive oxygen species (ROS) due to the efficient energy transfer between CS-UCNPs and VP. In a pilot preclinical study, intratumoral administration of nanoparticle conjugates to mice, followed by exposure to NIR light, induced necrosis of pancreatic tumor and suppressed its growth.

In this paper, we presented the unique optical properties of monodispersed and uniform luminescence nanothermometers (LNTs), composed of core (NaYF4:Yb3+,Er3+) and core-shell (NaYF4:Yb3+,Er3+@NaYF4) upconverting nanoparticles (UCNPs). We observed a significant influence of the NaYF4 shell on the reduction of the luminescence energy loss, which appeared as a steeper temperature vs. luminescence intensity ratio (I G2/I G1) curve. Moreover, the addition of nonionic IGEPAL CO-520 surfactant and a small amount of deionized water led to the additional improvement of the nanothermometer's sensitivity, especially in the physiological temperature range between 35 and 40 °C. Such behavior was explained by the physical and chemical interactions of the surfactant molecules with the particle surface, which led to a significant reduction in luminescent energy loss. The developed method of lanthanide-based LNT synthesis and characterization is suitable for the preparation of in vitro nanothermometers and could be applied, for example, in microelectronics or environmental monitoring.

One of the approaches to increase bioavailability and stability of hydrophobic biologically active compounds is their incorporation into polymer backbone. This work deals with the modification of chitosan (CS) with gossypol (GS), a phenolic compound with confirmed anticancer properties, by the free-radical grafting method. The series of the CS derivatives with increasing content of GS were prepared using pure GS or gossypol acetate (GSA) and compared to the control CS (cCS). The starting CS, cCS, and GS-containing derivatives were characterized using Fourier-transform infrared (FTIR), Raman, and 13C ssNMR spectroscopies; elemental and thermogravimetric analysis to evaluate the influence of the radicals and GS on the properties of polymers was performed. The Folin–Ciocalteu (F-C) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) methods were used to evaluate antioxidant properties of GS-modified CSs. Additionally, the polymer solubility and the specific viscosity of the solutions were determined. The content of GS in polymers raised proportionally with increasing amount of GS added to the reaction mixture, thereby enhancing the ability to scavenge free radicals. The type of GS used (GS or GSA) in polymers affected the degree of CS crosslinking (higher for pure GS), polymer solubility (lower for pure GS), the amount of grafted GS (~20% higher for GSA), and antioxidant properties in favor of GSA.

In the diagnostics of diabetes, specific targeting of drugs (e.g., liraglutide) to insulin-deficient β-cells with their simultaneous noninvasive imaging is currently needed. In this report, liraglutide (LGL)-conjugated poly(methyl vinyl ether-alt-maleic acid) (PMVEMA)-coated core-shell NaYF4:Yb,Er,Fe@NaYF4:Nd upconversion nanoparticles (CS-UCNPs) have been developed, thoroughly physicochemically characterized, and evaluated in vivo. Novel codoping of Fe2+, Yb3+, and Er3+ ions in the host NaYF4 induced upconversion emission in the red region at both 980 and 808 nm excitation, making the particles suitable for deep-tissue imaging. Surface functionalization with PMVEMA provided colloidal stability and facilitated covalent conjugation with LGL, enabling targeted binding to GLP-1 receptors on pancreatic β-cells, increasing glucose-stimulated insulin secretion from isolated Langerhans islets. Biocompatibility of CS-UCNP@PMVEMA-LGL nanoparticles was confirmed by the trypan blue dye exclusion assay. When the fluorescent dye Flamma was conjugated to the nanoparticles, in vivo fluorescence imaging revealed significantly enhanced accumulation of CS-UCNP@PMVEMA-LGL-Flamma nanoparticles in the pancreas 24 h after intramuscular injection compared with intravenous administration, with luminescence intensity approximately doubled. The improved pancreatic targeting efficiency was attributed to enhanced binding to GLP-1 receptors. Confocal microscopy and elemental analysis confirmed receptor-mediated uptake of the nanoparticles by internalization and their localization within pancreatic β-cells. These findings highlight the potential of CS-UCNP@PMVEMA-LGL nanoparticles as biocompatible targetable imaging agents with future applications in pancreatic diagnostics.

We describe a new concept for preparation of ultrasmall NaYF4:Yb,Er upconversion nanoparticles (UCNPs) with a diameter of 7 nm, depending on the amount of water added in the polymerization mixture, which affects the nucleation and growth of the particles. The morphology and structure of the nanoparticles were thoroughly characterized both in the dried state (TEM including elemental analysis and electron diffraction) and in solution (small and wide-angle X-ray scattering and dynamic light scattering). A thick NaYF4 shell was subsequently introduced onto the particles, which significantly increased the luminescence by minimizing surface quenching effects and passivating the core from the surrounding environment. To make the particles dispersible in the aqueous environment natural for biological applications, they were coated with a similar to 6 nm thick hydrophilic silica layer. This increased the size of core and core-shell UCNPs to 20 and similar to 50 nm. All the developed particles exhibited non-cytotoxicity tested in insulinoma INS-1E cells. The upconversion luminescence of these nanoparticles incubated with INS-1E cells showed a similar pattern to that of the particles themselves. The small biocompatible UCNPs developed in this study are promising candidates for non-invasive and non-destructive applications in bioimaging. Thanks to their advantageous properties, i.e., small size, adjustable optical properties and ability to interact with and easily penetrate cells, they are suitable for future use in platforms for targeted drug delivery and advanced diagnostic technologies.

Modifying scaffolds with agents that at the same time positively influence osteogenic cells and have a negative impact on cancerous growth, is a promising solution for patients with bone tissue defects following tumor excision. Such materials may not only boost tissue regeneration but also limit the risk of cancer reoccurrence. In our study, we developed novel bifunctional scaffolds containing magnetic nanoparticles grafted with PCL (MNP@PCL) and tannic acid (TA), which may be directed to support normal bone cells and suppress osteosarcoma cells. First, MNPs were postsynthetically surface-modified, by grafting poly(ε-caprolactone) (PCL) from the surface via ring opening polymerization of ε-caprolactone, to provide their uniform distribution within the polymer matrix. Then, fiber mats containing a fixed amount of MNPs (2 wt %) and increasing content of TA (0, 1, 5, and 10 wt %) were prepared by electrospinning method. Both MNP@PCL and TA decreased polymer crystallinity. The interaction between the MNPs and TA significantly influenced the mat morphology, thermal properties, and initial hydrolytic performance. The most intensive TA release was observed mainly within first 6 h of incubation, and it was 3.5-fold higher (ca. 0.02 mg of TA/per mg of mat) for mfPCL@TA-10 compared to mfPCL@TA-5. Moreover, TA-containing magnetic mats suppressed the metabolic activity of osteosarcoma cells. They also demonstrated enhanced antimicrobial properties against the bacteria typically accompanying orthopedic complications, reducing the population of Gram-positive bacteria by more than 90% compared to the neat PCL mat. This proves the high potential of these materials for combining cancer treatment with bone tissue engineering.

Early diagnosis and treatment of cancer is rapidly advancing thanks to the development of nanotechnology. Here, upconversion nanoparticles (UCNPs) are particularly promising as they are finding a wide range of applications in drug delivery and tumor imaging. In this report, a novel UCNP-based transport system is proposed for the delivery of the hypericin (Hyp) photosensitizer into malignant tumors. Core-shell NaYF4:Yb3+,Er3+@NaYF4:Nd3+ UCNPs were prepared by thermal decomposition and coated with poly(N,N-dimethylacrylamide-co-2-aminoethyl acrylate)-alendronate [P(DMA-AEA)-Ale], which endowed them with colloidal and chemical stability; finally, Hyp was conjugated. Internalization of CS-UCNP@P(DMA-AEA)-Ale-Hyp nanoparticles by Jurkat cells was successfully validated by multimodal imaging using a microstructural chamber, upconversion luminescence, and Raman microspectroscopy. After irradiation at 590 nm, CS-UCNP@P(DMA-AEA)-Ale-Hyp nanoparticles provided a markedly more effective photodynamic effect than Hyp alone at identical Hyp concentrations due to apoptosis as confirmed by caspase-3 activation. MTT assays showed that Hyp-free nanoparticles were non-cytotoxic, whereas CS-UCNP@P(DMA-AEA)-Ale-Hyp particles significantly reduced cell viability after irradiation. Considering that Hyp release from the nanoparticles was higher in the acidic environment typical of tumors compared to physiological ones, UCNP@P(DMA-AEA)-Ale-Hyp particles are a suitable candidate for future in vivo applications.

ABSTRACTThe aim of this study was to develop multifunctional magnetic poly(ε‐caprolactone) (PCL) mats with antibacterial properties for bone tissue engineering and osteosarcoma prevention. To provide good dispersion of magnetic iron oxide nanoparticles (IONs), they were first grafted with PCL using a novel three‐step approach. Then, a series of PCL‐based mats containing a fixed amount of ION@PCL particles and an increasing content of ascorbic acid (AA) was prepared by electrospinning. AA is known for increasing osteoblast activity and suppressing osteosarcoma cells. Composites were characterized in terms of morphology, mechanical properties, hydrolytic stability, antibacterial performance, and biocompatibility. AA affected both the fiber diameter and the mechanical properties of the nanocomposites. All produced mats were nontoxic to rat bone marrow‐derived mesenchymal cells; however, a composite with 5 wt.% of AA suppressed the initial proliferation of SAOS‐2 osteoblast‐like cells. Moreover, AA improved antibacterial properties against Staphylococcus aureus and Escherichia coli compared to PCL. Overall, these magnetic composites, reported for the very first time, can be used as scaffolds for both tissue regeneration and osteosarcoma prevention.

Pancreatic cancer is one of the most common forms of malignant disease with a poor survival prognosis. Currently, nanomedicine holds great promise for targeted diagnosis and treatment of this cancer, which also reduces toxic side effects. In this work, we prepared PEG-coated monodisperse upconversion nanoparticles (UCNPs) with a conjugated Flamma (R) fluorescent dye for imaging and detection of particle distribution in vivo. We performed a thorough physicochemical characterization of the particles and determined their colloidal and chemical stability in several aqueous media such as water, PBS, Dulbecco's modified Eagle's medium and artificial lysosomal fluid. Luminescence resonance energy transfer from the emission of UCNPs as a donor to the Flamma (R) as an acceptor was confirmed. Intraperitoneal versus intravenous administration was then compared in terms of biodistribution of particles in various organs in the orthotopic mice pancreatic cancer model. The intraperitoneal route was preferred over the intravenous one, because it significantly increased the accumulation of particles in the tumor tissue. These new UCNP@Ale-PEG-Flamma (R) nanoparticles are thus promising for new treatment avenues for pancreatic cancer.

In this study, spherical or hexagonal NaYF4:Yb,Er nanoparticles (UCNPs) with sizes of 25 nm (S-UCNPs) and 120 nm (L-UCNPs) were synthesized by high-temperature coprecipitation and subsequently modified with three kinds of polymers. These included poly(ethylene glycol) (PEG) and poly(N,N-dimethylacrylamide-co-2-aminoethylacrylamide) [P(DMA-AEA)] terminated with an alendronate anchoring group, and poly(methyl vinyl ether-co-maleic acid) (PMVEMA). The internalization of nanoparticles by rat mesenchymal stem cells (rMSCs) and C6 cancer cells (rat glial tumor cell line) was visualized by electron microscopy and the cytotoxicity of the UCNPs and their leaches was measured by the real-time proliferation assay. The comet assay was used to determine the oxidative damage of the UCNPs. An in vivo study on mice determined the elimination route and potential accumulation of UCNPs in the body. The results showed that the L- and S-UCNPs were internalized into cells in the lumen of endosomes. The proliferation assay revealed that the L-UCNPs were less toxic than S-UCNPs. The viability of rMSCs incubated with particles decreased in the order S-UCNP@Ale-(PDMA-AEA) > S-UCNP@Ale-PEG > S-UCNPs > S-UCNP@PMVEMA. Similar results were obtained in C6 cells. The oxidative damage measured by the comet assay showed that neat L-UCNPs caused more oxidative damage to rMSCs than all coated UCNPs while no difference was observed in C6 cells. An in vivo study indicated that L-UCNPs were eliminated from the body via the hepatobiliary route; L-UCNP@Ale-PEG particles were almost eliminated from the liver 96 h after intravenous application. Pilot fluorescence imaging confirmed the limited in vivo detection capabilities of the nanoparticles.

Magnetic nanoparticles (MNPs) modified with tannic acid (TA) have shown remarkable success as an antioxidant and antimicrobial therapeutic agent. Herein, we report a synthetic procedure for the preparation of silica-coated MNPs modified with N-acetylcysteine-modified chitosan and TA. This was achieved by free-radical grafting of NAC onto chitosan (CS), a layer-by-layer technique for modifying negatively charged MNP@SiO2 nanoparticles with positively charged CS-NAC, and crosslinking CS with TA. The antioxidant and metabolic effects of MNP@SiO2-CS-NAC and MNP@SiO2-CS-NAC-TA nanoparticles were tested in a model of prediabetic rats with hepatic steatosis, the hereditary hypertriglyceridemic rats (HHTg). The particles exhibited significant antioxidant properties in the liver, increasing the activity of the antioxidant enzymes superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GPx), decreasing the concentration of the lipoperoxidation product malondialdehyde (MDA), and improving the antioxidant status determined as the ratio of reduced to oxidized glutathione; in particular, TA increased some antioxidant parameters. MNPs carrying antioxidants such as NAC and TA could thus represent a promising therapeutic agent for the treatment of various diseases accompanied by increased oxidative stress.