Stimulus-Responsive Hydrogels as Drug Delivery Systems for Inflammation Targeted Therapy.

Deregulated inflammations induced by various factors are one of the most common diseases in people's daily life, while severe inflammation can even lead to death. Thus, the efficient treatment of inflammation has always been the hot topic in the research of medicine. In the past decades, as a potential biomaterial, stimuli-responsive hydrogels have been a focus of attention for the inflammation treatment due to their excellent biocompatibility and design flexibility. Recently, thanks to the rapid development of nanotechnology and material science, more and more efforts have been made to develop safer, more personal and more effective hydrogels for the therapy of some frequent but tough inflammations such as sepsis, rheumatoid arthritis, osteoarthritis, periodontitis, and ulcerative colitis. Herein, from recent studies and articles, the conventional and emerging hydrogels in the delivery of anti-inflammatory drugs and the therapy for various inflammations are summarized. And their prospects of clinical translation and future development are also discussed in further detail.

Nanomedicine for the Detection and Treatment of Ocular Bacterial Infections.

Ocular bacterial infection is a prevalent cause of blindness worldwide, with substantial consequences for normal human life. Traditional treatments for ocular bacterial infections areless effective, necessitating the development of novel techniques to enable accurate diagnosis, precise drug delivery, and effective treatment alternatives. With the rapid advancement of nanoscience and biomedicine, increasing emphasis has been placed on multifunctional nanosystems to overcome the challenges posed by ocular bacterial infections. Given the advantages of nanotechnology in the biomedical industry, it can be utilized to diagnose ocular bacterial infections, administer medications, and treat them. In this review, the recent advancements in nanosystems for the detection and treatment of ocular bacterial infections are discussed; this includes the latest application scenarios of nanomaterials for ocular bacterial infections, in addition to the impact of their essential characteristics on bioavailability, tissue permeability, and inflammatory microenvironment. Through an in-depth investigation into the effect of sophisticated ocular barriers, antibacterial drug formulations, and ocular metabolism on drug delivery systems, this review highlights the challenges faced by ophthalmic medicine and encourages basic research and future clinical transformation based on ophthalmic antibacterial nanomedicine.

Dual-channel lanthanide-doped nanoprobe for reliable multi-signal ratiometric detection of H2S in whole blood.

Wavelength-dependent absorbance of blood has impeded the development of fluorescence biodetection in whole blood. Here, by replacing the fluorescence working signal with a temperature signal, reliable H2S detection was performed in samples of whole blood. The developed system was based on a dual-channel lanthanide-doped nanoprobe, which further allowed precise serodiagnosis of acute pancreatitis.

Inflammation-Triggered Supramolecular Nanoplatform for Local Dynamic Dependent Imaging-Guided Therapy of Rheumatoid Arthritis.

The aging of population has resulted in a significant increase in the prevalence of rheumatoid arthritis (RA), which is a persistent and recurrent synovial inflammation caused by abnormal immune activation. Herein, the authors designed an inflammation-triggered disassembly (ITD) nanoplatform by a supramolecular assembly method, which controls the decomposition and drug release through changes in cytokine concentrations and redox potentials during the onset of arthritis, and its dual-targeted synergistic effect on collagen-induced arthritis (CIA) rats resulted in higher cell death rate and immunosuppressive rate. Meanwhile, they propose the local dynamic dependent imaging (LDDI) technology to diagnose the disease status, which may produce corresponding changes with the fluctuation of inflammatory activity and improve the accuracy of dual-target therapy by monitoring the synovial changes through in situ photoactivation of the second near infrared light (NIR-II). Very importantly, histological analysis shows that ITD strategy relieved joint destruction and cartilage degeneration and its clinical score is similar to that of the healthy group. Their work provides an effective strategy for the early diagnosis and treatment of acute and chronic inflammation diseases, which can interfere to abnormal immune activation, rather than affecting the normal function of immune system.

Customized Photothermal Therapy of Subcutaneous Orthotopic Cancer by Multichannel Luminescent Nanocomposites.

Photothermal therapy (PTT) is a potentially advanced strategy for highly precise cancer treatment. Tumor-microenvironment-activatable agents provide useful tools for PTT, but their photothermal conversion capacities vary and cannot be evaluated in vivo; thus, a general PTT prescription does not work with individual activatable agents. Here, glutathione (GSH)-activatable nanocomposites, silicomolybdate-functionalized NaLuF4 :Yb,Er@NaLuF4 @NaLuF4 :Nd are prepared, for customized PTT of subcutaneous orthotopic cancer. By simultaneously determining intratumoral GSH concentration and the amount of accumulated agent using multiple orthogonal luminescent emissions of nanocomposites, near-infrared absorbance of photothermal conversion agents is evaluated in vivo, based on the optimized irradiating prescriptions (irradiating power density and time) established. This allows customized PTT of each individual case with high efficacy and viability. This work also includes a method for investigating individual intratumoral variation, and the development of the next generation of customized nanomedicine for efficacious PTT of subcutaneous orthotopic cancer.

A Spontaneous Membrane-Adsorption Approach to Enhancing Second Near-Infrared Deep-Imaging-Guided Intracranial Tumor Therapy.

Herein, a functional class of microenvironment-associated nanomaterials is reported for improving the second near-infrared (NIR-II) imaging and photothermal therapeutic effect on intracranial tumors via a spontaneous membrane-adsorption approach. Specific peptides, photothermal agents, and biological alkylating agents were designed to endow the nanogels with high targeting specificity, photothermal properties, and pharmacological effects. Importantly, the frozen scanning electron microscopy technology (cryo-SEM) was utilized to observe the self-association of nanomaterials on tumor cells. Interestingly, the spontaneous membrane-adsorption behavior of nanomaterials was captured through direct imaging evidence. Histological analysis showed that the cross-linking adhesion in intracranial tumor and monodispersity in normal tissues of the nanogels not only enhanced the retention time but also ensured excellent biocompatibility. Impressively, in vivo data confirmed that the microenvironment-associated nanogels could significantly enhance brain tumor clearance rate within a short treatment timeframe (only two weeks). In short, utilizing the spontaneous membrane-adsorption strategy can significantly improve NIR-II diagnosis and phototherapy in brain diseases while avoiding high-risk complications.

Microenvironment-Triggered Degradable Hydrogel for Imaging Diagnosis and Combined Treatment of Intraocular Choroidal Melanoma.

Human choroidal melanoma (HCM) is one of the most common primary intraocular tumors and easily provokes liver metastases owing to the lack of sensitive and noninvasive therapeutic methods. Concerning the imaging diagnostics and therapeutic predicaments for choroidal melanoma, we designed microenvironment-triggered degradable hydrogels (RENP-ICG@PNIPAM:Dox-FA) based on ultrasmall (<5 nm) rare-earth nanoparticles (RENPs) with enhanced NIR-II luminescence. The ultrasmall diameter can significantly enhance the NIR-II luminescence performance of RENPs. RENPs were encapsulated by a dual-response PNIPAM hydrogel, which could release drug by responding to heat energy and glutathione under the tumor microenvironment. The in vitro/in vivo NIR-II imaging detection and antitumor activity were also compared systematically after different treatment conditions on ocular choroidal melanoma-1 cells and tumor-bearing mice, respectively. Besides, the degradability of the hydrogel composites under physiological conditions could be conducive to enhance the photothermal-chemotherapeutic effect and alleviate long-term biological toxicity. Our work on the microenvironment-triggered hydrogels with enhanced NIR imaging and easy metabolism may provide a promising strategy for sensitive and noninvasive imaging and phototherapy in ocular tumors.

Enantioselective NHC-Catalyzed [3+3] Annulation of α-Bromoenals with 2-Aminobenzimidazoles.

A chiral carbene-catalyzed [3+3] annulation of α-bromoenals with 2-aminobenzimidazoles providing pyrimido[1,2-a]benzimidazoles has been described. This protocol features a broad scope and good functional group tolerance. Biological studies indicated that the formed pyrimido[1,2-a]benzimidazole exhibited moderate cytotoxic activity against tumor cells.

DNA-templated porous nanoplatform towards programmed "double-hit" cancer therapy via hyperthermia and immunogenicity activation.

Photothermal therapy, assisted with long-term immunological anti-tumor effect, has great potential in clinical medical practice. Herein, a brand new DNA-template hydrothermal method was developed to prepare novel Co9S8 nanoplatform with outstanding hydrophily and mesoporous internal structure. Based on the mesoporous Co9S8 nanoplatform, MRI-guided enhanced photothermal-immunology "double-hit" synergistic cancer therapy was achieved, through the HSP90 inhibition and immunology activation effect of the loaded epigallocatechin gallate and oxaliplatin. It is noteworthy that the drugs were stepwise released from the nanoplatform under the trigger of pH and heat, respectively. More importantly, the high efficient synergistic cancer therapy and long-term immunological anti-tumor effect were confirmed in vivo. The developed porous nanoplatform, taking accounts of both high efficient tumor ablation and long-term anti-tumor effect, provide a new strategy to the development of next generation nanomedicine for clinical cancer treatment.

Naturally occurring nanotube with surface modification as biocompatible, target-specific nanocarrier for cancer phototherapy.

Phototherapy has drawn increasing attention including the use of nanocarriers with high drug loading capacity and delivery efficacy for target-specific therapy. We have made use of naturally-occurring halloysite nanotubes (HNTs) to build a biomimetic nanocarrier platform for target-specific delivery of phototherapeutic agents. The HNTs were decorated with poly(sodium-p-styrenesulfonate) (PSS) to enhance the biocompatibility, and were further functionalized by lumen loading the type-II photosensitizer indocyanine green (ICG). The HNT-PSS-ICG nanocarrier, without further tethering targeting groups, was shown to associate with the membrane of giant unilamellar vesicles (GUVs) via Pickering effects. Application of HNT-PSS-ICG nanocarrier to human breast cancer cells gave rise to a cell mortality as high as 95%. The HNT-PSS-ICG nanocarrier was further coated with MDA-MB-436 cell membranes to endow it with targeting therapy performance against breast cancer, which was confirmed by in vivo experiments using breast cancer tumors in mice. The membrane-coated and biocompatible nanocarrier preferentially concentrated in the tumor tissue, and efficiently decreased the tumor volume by a combination of photodynamic and photothermal effects upon near-infrared light exposure. Our results demonstrate that the HNT-based nanocarrier by virtue of facial preparation and high loading capacity can be a promising candidate for membrane-targeting nanocarriers.

Energy transfer mechanism dominated by the doping location of activators in rare-earth upconversion nanoparticles.

Research on the energy transfer mechanism of rare-earth-doped upconversion nanoparticles (UCNPs) has been an important area due to the increasing demand for tuning multicolor emission and enhancing the upconversion efficiency; however, because of large energy mismatch, many lanthanide activators, such as Eu3+, cannot realize highly efficient near infrared-to-visible upconversion by simple codoping of Yb3+. Therefore, introduction of other ions to assist the energy transfer process is required. Herein, we prepared core-shell nanoparticles with different doping locations to investigate the upconversion energy transfer mechanism. The upconversion luminescence (UCL) of core-shell nanoparticles was investigated by steady-state luminescence and time-resolved luminescence spectra. The UCL behaviors in these different multi-activator core-shell nanoparticles were observed. The results revealed different energy transfer channels influenced by the doping location of activators. This study may open up new avenues of structure design for fine-tuning of multicolor UCL for specific applications.

Study on the Fluorescent Activity of N²-Indolyl-1,2,3-triazole.

A new type of blue emitter, N²-Indolyl-1,2,3-triazoles (NITs), with the λmax ranging from 420-480 nm and the Stokes shift from 89-143 nm, were synthesized through the coupling reaction of indoles with triazole derivatives. The influence of different substitution patterns on the optical properties (efficiency, excitation, and emission wavelengths) of the NITs was investigated. In addition, one palladium complex were synthesized by using NITs as the ligands, which, however, exhibited no fluorescent activity, but did show the enhanced co-planarity. Lastly, two bio-active molecule derivatives were explored for the potential use of these novel dyes in related chemical and biological applications.

Design and Fabrication of Temperature-Sensitive Nanogels with Controlled Drug Release Properties for Enhanced Photothermal Sterilization.

For better removal of excessive free radicals and harmful bacteria from the human body, the development of synergistic antioxidant and antibacterial agents is urgently required. Herein, we designed novel temperature-sensitive, curcumin (Cur)-loaded nanogels for the application of scavenging reactive oxygen species and killing pathogenic bacteria. Photothermal sterilization, different from traditional antibiotics, is a promising and effective treatment for pathogenic bacterial infection. The nanogels were fabricated by using poly(N-isopropylacrylamide) (a temperature-sensitive hydrogel) to encapsulate poly(3,4-ethylenedioxythiophene) nanoparticles (photothermal agents) and Cur through a reformative precipitation polymerization. When triggered by near-IR light, the Cur-loaded nanogels exhibited high (56.8 %), and excellent temperature-sensitive effects. Moreover, the light-induced temperature increase can also weaken the interaction between the networks of PNIPAAm and Cur, to show excellent antioxidant and antibacterial performance (90 % cell death) of the nanogels.

DNA-assisted upconversion nanoplatform for imaging-guided synergistic therapy and laser-switchable drug detoxification.

The side effects of chemotherapy bring significant physical and psychological suffering to patients. To solve this urgent medical problem, Yb3+ and Er3+ co-doped NaLuF4 upconversion nanoparticles (UCNPs) were constructed for upconversion luminescence (UCL)-labeled diagnosis under 980 nm laser irradiation. The UCNPs were then modified layer by layer with polypyrrole and a special programming DNA segment as photothermal conversion agents and controllable drug carriers, respectively. The nanoplatform was successfully used for imaging-guided synergistic therapy (photothermal therapy and chemotherapy) at a safe power density (300 mW cm-2), and DNA-assisted detoxification at lower temperature in cancer cells when the laser off. The synergistic therapy of the nanoplatform achieved a higher therapeutic index (∼85%) than chemotherapy only (∼44%) and photothermal therapy only (∼25%) in vitro. In vivo experiments also suggested that the nanoplatform had a higher therapeutic effect and lower side effects. The toxicity study was also evaluated, indicating the nanoplatform is low toxic to living system. This multifunctional upconversion nanoplatform provided an innovative method for imaging-guided photothermal-chemotherapy and laser-switchable drug detoxification.

Polyaniline-coated upconversion nanoparticles with upconverting luminescent and photothermal conversion properties for photothermal cancer therapy.

In this study, we developed a nanosystem based on upconversion nanoparticles (UCNPs) coated with a layer of polyaniline nanoparticles (PANPs). The UCNP induces upconversion luminescence for imaging and photothermal conversion properties are due to PANPs. In vitro experiments showed that the UCNPs-PANPs were nontoxic to cells even at a high concentration (800 µg mL(-1)). Blood analysis and histological experiments demonstrated that the UCNPs-PANPs exhibited no apparent toxicity in mice in vivo. Besides their efficacy in photothermal cancer cell ablation, the UCNP-PANP nanosystem was found to achieve an effective in vivo tumor ablation effect after irradiation using an 808 nm laser. These results demonstrate the potential of the hybrid nanocomposites for use in imaging-guided photothermal therapy.

Novel Cs-Based Upconversion Nanoparticles as Dual-Modal CT and UCL Imaging Agents for Chemo-Photothermal Synergistic Therapy.

Lanthanide-based contrast agents have attracted increasing attention for their unique properties and potential applications in cancer theranostics. To date, many of these agents have been studied extensively in cells and small animal models. However, performance of these theranostic nanoparticles requires further improvement. In this study, a novel CsLu2F7:Yb,Er,Tm-based visual therapeutic platform was developed for imaging-guided synergistic cancer therapy. Due to the presence of the heavy alkali metal Cesium (Cs) in host lattice, the nanoplatform can provide a higher resolution X-ray CT imaging than many other reported lanthanide-based CT contrast agents. Furthermore, by using the targeted RGD motif, chemotherapy drug alpha-tocopheryl succinate (α-TOS), and photothermal coupling agent ICG, this nanoplatform simultaneously provides multifunctional imaging and targeted synergistic therapy. To demonstrate the theranostic performance of this novel nanoplatform in vivo, visual diagnosis in the small animal model was realized by UCL/CT imaging which was further integrated with targeted chemo-photothermal synergistic therapy. These results provided evidence for the successful construction of a novel lanthanide-based nanoplatform coupled with multimodal imaging diagnosis and potential application in synergistic cancer theranostics.

PEDOT nanocomposites mediated dual-modal photodynamic and photothermal targeted sterilization in both NIR I and II window.

PEDOT nanoparticles with a suitable nanosize of 17.2 nm, broad adsorption from 700 to 1250 nm, and photothermal conversion efficiency (η) of 71.1%, were synthesized using an environmentally friendly hydrothermal method. Due to the electrostatic attraction between indocyanine green (ICG) and PEDOT, the stability of ICG in aqueous solution was effectively improved. The PEDOT nanoparticles modified with glutaraldehyde (GTA) targeted bacteria directly, and MTT experiments demonstrated the low toxicity of PEDOT:ICG@PEG-GTA in different bacteria and cells. Pathogenic bacteria were effectively killed by photodynamic therapy (PDT) and photothermal therapy (PTT) with PEDOT:ICG@PEG-GTA in the presence of near-infrared (NIR) irradiation (808 nm for PDT, and 1064 nm for PTT). The combination of the two different bacteriostatic methods was significantly more effective than PTT or PDT alone. The obtained PEDOT:ICG@PEG-GTA may be used as a novel synergistic agent in combination photodynamic and photothermal therapy to inactivate pathogenic bacteria in both the NIR I and II window.