Preparation and in vitro evaluation of protective effects of Silibinin-loaded polymeric micelles on human hair against UV-B radiation.

BACKGROUND: The purpose of this study was to investigate the protective effect of Silibinin-loaded polymeric micelles from human hair against UV-B radiation. METHODS: Eight formulations with different concentrations of Silibinin, Pluronic F-127, and Labrasol-Labrafil were made by a solvent evaporation method, and the selected formulation was chosen by examining their properties like particle size and loading efficiency. Six groups of human hair, including a group that received the selected formulation, were exposed to UV-B radiation and by calculating its factors such as peak-to-valley roughness, RMS roughness, FTIR, and the amount of protein loss, the protective effect of the selected formulation was judged. RESULTS: According to the results, the loading efficiency and particle size of the selected formulation were 45.34% and 43.19 nm. The Silibinin release profile had two parts, fast and slow, which were suitable for creating a drug depot on hair. Its zeta potential also confirmed the minimum electrostatic interference between the formulation and hair surface. The zeta potential of selected formulation was -5.9 mv. Examination of AFM images showed that the selected formulation was able to prevent the increase in peak-to-valley roughness and RMS roughness caused by UV-B radiation. RMS roughness after 600 h of UV radiation in Groups 5 and 6 was significantly lower than the negative control group and the amount of this factor did not differ significantly between 0 and 600, so it can be concluded that the selected formulation containing Silibinin and the positive control group was able to prevent the increase of RMS roughness and hair destruction. In other hands, the two positive control groups and the selected formulation containing Silibinin were able to effectively reduce hair protein loss. CONCLUSION: Silibinin-loaded polymeric micelles were able to effectively protect hair from structural and chemical changes caused by UV-B radiation.

Bifunctional Smart Hydrogel Dressing with Strain Sensitivity and NIR-Responsive Performance.

Smart response hydrogel has a broad application prospect in human health real-time monitoring due to its responses to a variety of stimuli. In this study, we developed a novel smart hydrogel dressing based on conductive MXene nanosheets and a temperature-sensitive PNIPAm polymer. γ-Methacryloxypropyltrimethoxysilane (KH570) was selected to functionalize the surface of MXene further to improve the interface compatibility between MXene and PNIPAm. Our prepared K-M/PNIPAm hydrogel was found to have a strain-sensitive property, as well as a respond to NIR phase change and volume change. When applied as a strain flexible sensor, this K-M/PNIPAm hydrogel exhibited a high strain sensitivity with a gauge factor (GF) of 4.491, a broad working strain range of ≈250%, a fast response of ∼160 ms, and good cycle stability (i.e., 3000 s at 20% strain). Besides, this K-M/PNIPAm hydrogel can be used as an efficient NIR light-controlled drug release carrier to achieve on-demand drug release. This work paved the way for the application of smart response hydrogel in human health real-time monitoring and NIR-controlled drug release functions.

Hypericin-loaded oil-in-water nanoemulsion synthesized by ultrasonication process enhances photodynamic therapy efficiency.

Hypericin (Hy) is a hydrophobic photosensitizer used in photodynamic therapy for cancer therapeutic. In this study, Hy-loaded oil-in-water (O/W) nanoemulsions (NEs) were produced by the ultrasonication method combing different biocompatible oils and surfactants to enhance Hy aqueous solubility and bioavailability. Experimental parameters were optimized by the characterization of droplet size, zeta potential, and physicochemical properties. In vitro studies based on the release profile, cytotoxicity, cell morphology, and Hy intracellular accumulation were assayed. Hy at 100 mg L-1 was incorporated into the low viscosity (~0.005 Pa s) NEs with spherical droplets averaging 20-40 nm in size and polydispersity index <0.02. Hy release from the NE was significantly higher (4-fold) than its suspension (p < 0.001). The NEs demonstrated good physical stability during storage at 5 °C for at least six months. The Hy-loaded NEs exhibited an IC50 value 6-fold lower than Hy suspension during PDT against breast cancer cell lines (MCF-7). Cell microscopy imaging confirmed the increased cytotoxic effects of Hy-loaded NEs, showing damaged and apoptotic cells. Confocal laser scanning microscopy evidenced greater Hy delivery through NE into MCF-7 cells followed by improved intracellular ROS generation. Our results suggest that the Hy-loaded NEs can improve hypericin efficacy and assist Hy-PDT's preclinical development as a cancer treatment.

Green Light-Triggered Intraocular Drug Release for Intravenous Chemotherapy of Retinoblastoma.

Retinoblastoma is one of the most severe ocular diseases, of which current chemotherapy is limited to the repetitive intravitreal injections of chemotherapeutics. Systemic drug administration is a less invasive route; however, it is also less efficient for ocular drug delivery because of the existence of blood-retinal barrier and systemic side effects. Here, a photoresponsive drug release system is reported, which is self-assembled from photocleavable trigonal small molecules, to achieve light-triggered intraocular drug accumulation. After intravenous injection of drug-loaded nanocarriers, green light can trigger the disassembly of the nanocarriers in retinal blood vessels, which leads to intraocular drug release and accumulation to suppress retinoblastoma growth. This proof-of-concept study would advance the development of light-triggered drug release systems for the intravenous treatment of eye diseases.

Design and Synthesis of New PEGylated Polydopamine-Based Nanoconstructs Bearing ROS-Responsive Linkers and a Photosensitizer for Bimodal Photothermal and Photodynamic Therapies against Cancer.

Polydopamine (PDA) nanoparticles (NPs) have recently acquired considerable attention for the development of nanoplatforms with multifunctional properties including photothermal (PTT) and photodynamic (PDT) activities. In addition to their high PTT performance, they can be easily conjugated to different types of photosensitizers (PSs) to acquire PDT activity. However, because of PDA free-radical scavenging properties, grafting the PSs directly to PDA surfaces may lead to an inefficient PDT outcome. Thus, the present work aims at synthesizing and characterizing a new PEGylated PDA-based nanoplatform with bifunctional PTT and PDT properties, which allows bimodal cancer therapy with the possibility to release the PS on demand in a spatiotemporal fashion. To do so, PDA NPs with a well-defined size and shape were prepared by the auto-oxidative self-polymerization process of dopamine hydrochloride in mild alkaline solution. The impact of the size on the PTT conversion efficiency was then determined. This allowed us to choose the optimal PDA NP size for PTT applications. Next, PDA NPs were decorated with SH-PEG polymers that bear at their extremity a thioketal reactive oxygen species-cleavable linker coupled to trisulfonated-tetraphenylporphyrin (TPPS3) chosen as a hydrophilic PS. The grafting efficiency of PS-conjugated PEG on PDA was demonstrated in situ using a quartz crystal microbalance with dissipation monitoring. In addition, the photoinduced release of the PS was demonstrated by 1H NMR. Finally, PTT/PDT bimodal therapy was assessed in vitro on human squamous esophageal cells by illuminating the PDA NPs at two different wavelengths, which showed the strong synergistic effect of combining PTT and PDT within this nanoplatform.

Cyclodextrin Nanosponges Inclusion Compounds Associated with Gold Nanoparticles for Potential Application in the Photothermal Release of Melphalan and Cytoxan.

This article describes the synthesis and characterization of ß-cyclodextrin-based nano-sponges (NS) inclusion compounds (IC) with the anti-tumor drugs melphalan (MPH) and cytoxan (CYT), and the addition of gold nanoparticles (AuNPs) onto both systems, for the potential release of the drugs by means of laser irradiation. The NS-MPH and NS-CYT inclusion compounds were characterized using scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), energy dispersive spectroscopy (EDS), thermogravimetric analysis (TGA), UV-Vis, and proton nuclear magnetic resonance (1H-NMR). Thus, the inclusion of MPH and CYT inside the cavities of NSs was confirmed. The association of AuNPs with the ICs was confirmed by SEM, EDS, TEM, and UV-Vis. Drug release studies using NSs synthesized with different molar ratios of ß-cyclodextrin and diphenylcarbonate (1:4 and 1:8) demonstrated that the ability of NSs to entrap and release the drug molecules depends on the crosslinking between the cyclodextrin monomers. Finally, irradiation assays using a continuous laser of 532 nm showed that photothermal drug release of both MPH and CYT from the cavities of NSs via plasmonic heating of AuNPs is possible.

Azo modified hyaluronic acid based nanocapsules: CD44 targeted, UV-responsive decomposition and drug release in liver cancer cells.

Herein, we demonstrate a novel UV-induced decomposable nanocapsule of natural polysaccharide (HA-azo/PDADMAC). The nanocapsules are fabricated based on layer-by-layer co-assembly of anionic azobenzene functionalized hyaluronic acid (HA-azo) and cationic poly diallyl dimethylammonium chloride (PDADMAC). When the nanocapsules are exposed to 365 nm light, ultraviolet photons can trigger the photo-isomerization of azobenzene groups in the framework. The nanocapsules could decompose from large-sized nanocapsules to small fragments. Due to their optimized original size (~180 nm), the nanocapsules can effectively avoid biological barriers, provide a long blood circulation and achieve high tumor accumulation. It can fast eliminate nanocapsules from tumor and release the loaded drugs for chemotherapy after UV-induced dissociation. Besides, HA is an endogenous polysaccharide that shows intrinsic targetability to CD44 receptors on surface of cancer cells. The intracellular experiment shows that the HA-azo/PDADMAC nanocapsules with CD44 targeting ability and UV-controlled intracellular drug release are promising for cancer chemotherapy.

Intelligent phototriggered nanoparticles induce a domino effect for multimodal tumor therapy.

Rationale: Integration of several monotherapies into a single nanosystem can produce remarkable synergistic antitumor effects compared with separate delivery of combination therapies. We developed near-infrared (NIR) light-triggered nanoparticles that induce a domino effect for multimodal tumor therapy. Methods: The designed intelligent phototriggered nanoparticles (IPNs) were composed of a copper sulfide-loaded upconversion nanoparticle core, a thermosensitive and photosensitive enaminitrile molecule (EM) organogel shell loaded with anticancer drugs, and a cancer cell membrane coating. Irradiation with an NIR laser activated a domino effect beginning with photothermal generation by copper sulfide for photothermal therapy that also resulted in phase transformation of the EM gel to release the anticancer drug. Meanwhile, the NIR light energy was converted to ultraviolet light by the upconversion core to excite the EM, which generated reactive oxygen species for photodynamic therapy. Results: IPNs achieved excellent antitumor effects in vitro and in vivo with little systemic toxicity, indicating that IPNs could serve as a safe and high-performance instrument for synergetic antitumor therapy. Conclusion: This intelligent drug delivery system induced a chain reaction generating multiple antitumor therapies after a single stimulus.

Synthesis of a gemcitabine-modified phospholipid and its subsequent incorporation into a single microbubble formulation loaded with paclitaxel for the treatment of pancreatic cancer using ultrasound-targeted microbubble destruction.

Gemcitabine and nab-paclitaxel (Abraxane®) is a standard of care chemotherapy combination used in the treatment of patients with advanced pancreatic cancer. While the combination has shown a survival benefit when compared to gemcitabine monotherapy, it is associated with significant off-target toxicity. Ultrasound targeted microbubble destruction (UTMD) has emerged as an effective strategy for the site-specific deposition of drug-payloads. However, loading a single microbubble formulation with two drug payloads can be challenging and often involves several manipulations post-microbubble preparation that can be cumbersome and generally results in low / inconsistent drug loadings. In this manuscript, we report the one-pot synthesis of a gemcitabine functionalised phospholipid and use it to successfully generate stable microbubble formulations loaded with gemcitabine (Lipid-Gem MB) or a combination of gemcitabine and paclitaxel (Lipid-Gem-PTX MB). Efficacy of the Lipid-Gem MB and Lipid-Gem-PTX MB formulations, following ultrasound (US) stimulation, was evaluated in a three-dimensional (3D) PANC-1 spheroid model of pancreatic cancer and a mouse model bearing ectopic BxPC-3 tumours. The results demonstrated a significant reduction in the cell viability in spheroids for both formulations reducing from 90 ± 10% to 62 ± 5% for Lipid-Gem MB and 84 ± 10% to 30 ± 6% Lipid-Gem-PTX MB following US irradiation. When compared with a clinically relevant dose of free gemcitabine and paclitaxel (i.e. non-particle bound) in a BxPC-3 murine pancreatic tumour model, both formulations also improved tumour growth delay with tumours 40 ± 20% and 40 ± 30% smaller than the respective free drug formulation when treated with Lipid-Gem MB and Lipid-Gem-PTX MB respectively, at the conclusion of the experiment. These results highlight the potential of UTMD mediated Gem / PTX as a treatment for pancreatic cancer and the facile preparation of Lipid-Gem-PTX MBs using a gemcitabine functionalised lipid should expedite clinical translation of this technology.

Preparation of carbon dots-hematite quantum dots-loaded hydroxypropyl cellulose-chitosan nanocomposites for drug delivery, sunlight catalytic and antimicrobial application.

In this project, we studied the thermal and chemical method for the synthesis of carbon dots (CDs)/Hematite (α-Fe2O3) quantum dots and the preparation of hydroxypropyl cellulose cross-linked chitosan (HPCCS) and ulvan (UN) was performed by chemical method. Carbon dots/α-Fe2O3 quantum dots with size distribution of 3-5 nm were completely encapsulated in the HPCCS/UN NPs to obtain composites, which indicated unique characteristics with respect to antimicrobial, pH-responsive and optical properties. The CDs-HQDs/HPCCS/UN nanocomposites exhibited a single-excitation (440 nm), dual-emission fluorescence property (505 nm and 628 nm for green and red light from CDs-HQDs and HPCCS/UN NPs). The nanocomposites played as a pH-responsive drug delivery process to release ulvan at a fast rate in pH 7.4 buffer solution but at a slow rate in low pH solutions. The CDs-HQDs/HPCCS/UN nanocomposites gained the highest photocatalytic activity for degrading 4-chlorophenol (4-CPh) as a pollutant (>98% during 70 min under sunlight irradiation). Moreover, the nanocomposites indicated great inhibitory influences towards bacterial and fungal.

Red Light-Triggered Intracellular Carbon Monoxide Release Enables Selective Eradication of MRSA Infection.

Carbon monoxide (CO) is an important gaseous signaling molecule. The use of CO-releasing molecules such as metal carbonyls enables the elucidation of the pleiotropic functions of CO. Although metal carbonyls show a broad-spectrum antimicrobial activity, it remains unclear whether the bactericidal property originates from the transition metals or the released CO. Here, we develop nonmetallic CO-releasing micelles via a photooxygenation mechanism of 3-hydroxyflavone derivatives, enabling CO release under red light irradiation (e.g., 650 nm). Unlike metal carbonyls that non-specifically internalize into both Gram-positive and Gram-negative bacteria, the nonmetallic micelles are selectively taken up by S. aureus instead of E. coli cells, exerting a selective bactericidal effect. Further, we demonstrate that the CO-releasing micelles can cure methicillin-resistant S. aureus (MRSA)-infected wounds, simultaneously eradicating MRSA pathogens and accelerating wound healing.

Combining Mechanical High-Intensity Focused Ultrasound Ablation with Chemotherapy for Augmentation of Anticancer Immune Responses.

As a noninvasive therapy, high-intensity focused ultrasound (HIFU) shows great potential in inducing anticancer immune responses. However, the overall anticancer efficacy of HIFU is still limited due to the rapid attenuation of ultrasound waves and inadequacy of ultrasound waves to spread to the whole tumor. Here, we combined HIFU with the ultrasound contrast agent/chemotherapeutic drug co-delivery nanodroplets to achieve synergistic enhancement of anticancer efficacy. Different from the widely used thermal HIFU irradiation, by which excessive heating would result in inactivation of immune stimulatory molecules, we used short acoustic pulses to trigger HIFU (mechanical HIFU, mHIFU) to improve anticancer immune responses. The nanodroplets displayed a mHIFU/glutathione (GSH)-dual responsive drug release property, and their cellular uptake efficacy and toxicity against cancer cells increased upon mHIFU irradiation. The generated immunogenic debris successfully induced the exposure of damage-associated molecular patterns on the cell surface for dendritic cells (DCs) maturation. In vivo experiments with tumor-bearing mice showed that the co-delivery nanodroplets in combination with mHIFU could effectively inhibit tumor growth by inducing immunogenic cell death, activating DCs maturation, and enhancing the effector T-cell infiltration within tumors. This work reveals that combined treatment with nanodroplets and mHIFU is a promising approach to eradicate tumors.

[Drug Release System Controlled by Photothermal Effect of Gold Nanoparticles].

Controlled drug release in response to light irradiation is an important technique for focusing drug elution to specific sites and reducing the side effects of drugs in normal tissue. In one example, we used double-stranded DNA to modify gold nanorods. When the gold nanorods were heated by irradiation with near-infrared light, single-stranded DNA was released. Thus, we successfully prepared a controlled release system that responds to near-infrared irradiation by combining heat-labile linkers such as double-stranded DNA. However, the drug-loading capacity on the surface of the nanoparticles was limited. To improve the loading efficiency, we encapsulated gold nanorods in poly(lactic-co-glycolic acid) (PLGA) nanoparticles, where PLGA acted as a drug payload. When the gold nanorod-containing PLGA nanoparticles were irradiated with a near-infrared laser, the PLGA nanoparticles were destroyed and significant drug release was observed. In another example, silver nanoplates were used as a near-infrared responsive photothermal nanodevice. Silver nanoparticles show antimicrobial activity that we expected could be controlled by light irradiation. First, we coated the silver nanoplates with gold atoms to mask the antimicrobial activity. When the gold-coated silver nanoplates were irradiated with a near-infrared pulsed laser, the shape of the silver nanoplates changed from plate-like to spherical, and silver ions were released. As a result, the antibacterial activity of the silver nanoplates was recovered. In this review, we outline examples of controlled release systems that respond to light irradiation. We believe that this review will contribute to improving the efficiency and safety of chemotherapy.

On-Demand Reversible UV-Triggered Interpenetrating Polymer Network-Based Drug Delivery System Using the Spiropyran-Merocyanine Hydrophobicity Switch.

A reversible switchable on-demand UV-triggered drug delivery system (DDS) based on interpenetrating polymer networks (IPNs) with silicone as the host polymer and spiropyran (SP)-functionalized guest polymer is designed and demonstrated. The photo-responsive IPNs provide a new triggered drug delivery concept as they exploit the change in intermolecular interactions (work of adhesion) among the drug, matrix, and solvent when the incorporated hydrophobic SP moieties transform into the hydrophilic merocyanine form upon light irradiation without degradation and disruption of the DDS. The change in how the copolymer composition (hydrophilicity and content) and the lipophilicity of the drug (log P) affect the release profile was investigated. A thermodynamic model, based on Hansen solubility parameters, was developed to design and optimize the polymer composition of the IPNs to obtain the most efficient light-triggered drug release and suppression of the premature release. The developed IPNs showed excellent result for dopamine, l-dopa, and prednisone with around 90-95% light-triggered release. The model was applied to study the release behavior of drugs with different log P and to estimate if the light-induced hydrophobic-to-hydrophilic switch can overcome the work of adhesion between polymers and drugs and hence the desorption and release of the drugs. To the best of our knowledge, this is the first time that work of adhesion is used for this aim. Comparing the result obtained from the model and experiment shows that the model is useful for evaluating and estimating the release behavior of specific drugs merocyanine, IPN, DDS, and spiropyran.

Lipid-encapsulated upconversion nanoparticle for near-infrared light-mediated carbon monoxide release for cancer gas therapy.

Cancer gas therapy is just in an early stage of research and development. Several important gasotransmitters have proven their therapeutic potentials, but handling, delivery and controlled release of these gases remain very challenging for therapeutic purposes. This research develops a versatile nanosystem that is capable of delivering carbon monoxide (CO) gasotransmitter in the form of photo-responsive carbon monoxide-releasing molecule (CORM) for targeted cancer therapy. The core-shell upconversion nanoparticles (UCNPs) were designed to transfer bio-friendly low energy near infrared (NIR) light to ultraviolet (UV) light and trigger CO release from the loaded CORM. The synthesized delivery system demonstrated its ability to mediate the sustained release of CO upon 808 or 980 nm NIR light excitation. The optimized nanoformulation was efficiently taken up by HCT116 cancer cells and showed dose-dependent cytotoxicity to HCT116 and other cancer cells. Intracellular CO release and subsequent therapeutic action involving ROS production were found to significantly contribute to cell apoptosis. Therefore, the current research demonstrates the potency and efficiency of an NIR-mediated UCNP-based CORM prodrug delivery system for targeted cancer gas therapy.

Construction of a Mesoporous Polydopamine@GO/Cellulose Nanofibril Composite Hydrogel with an Encapsulation Structure for Controllable Drug Release and Toxicity Shielding.

The development of intelligent and multifunctional hydrogels having photothermal properties, good mechanical properties, sustained drug release abilities with low burst release, antibacterial properties, and biocompatibility is highly desirable in the biomaterial field. Herein, mesoporous polydopamine (MPDA) nanoparticles wrapped with graphene oxide (GO) were physically cross-linked in cellulose nanofibril (CNF) hydrogel to obtain a novel MPDA@GO/CNF composite hydrogel for controllable drug release. MPDA nanoparticles exhibited a high drug loading ratio (up to 35 wt %) for tetracycline hydrochloride (TH). GO was used to encapsulate MPDA nanoparticles for extending the drug release time and reinforcing the physical strength of the obtained hydrogel. The mechanical strength of the as-fabricated MPDA@GO/CNF composite hydrogel was five times greater compared to that of the pure CNF hydrogel. Drug release experiments demonstrated that burst release behavior was significantly reduced by adding MPDA@GO. The drug release time of the MPDA@GO/CNF composite hydrogel was 3 times and 7.2 times longer than that of the polydopamine/CNF hydrogel and pure CNF hydrogel, respectively. The sustained and controlled drug release behaviors of the composite hydrogel were highly dependent on the proportion of MPDA and GO. Moreover, the rate of drug release could be accelerated by near-infrared (NIR) light irradiation and pH value change. The drug release kinetics of the as-prepared composite hydrogel was well described by the Korsmeyer-Peppas model, and the drug release mechanism of TH from the composite hydrogel was anomalous transport. Importantly, this carefully designed MPDA@GO/CNF composite hydrogel showed good biocompatibility through an in vitro cytotoxicity test. In particular, the toxicity of GO was well shielded by the CNF hydrogel. Therefore, this novel MPDA@GO/CNF composite hydrogel with an encapsulation structure for controllable drug release and toxicity shielding of GO could be used as a very promising controlled drug delivery carrier, which may have potential applications for chemical and physical therapies.

Photo-Responsive Supramolecular Micelles for Controlled Drug Release and Improved Chemotherapy.

Development of stimuli-responsive supramolecular micelles that enable high levels of well-controlled drug release in cancer cells remains a grand challenge. Here, we encapsulated the antitumor drug doxorubicin (DOX) and pro-photosensitizer 5-aminolevulinic acid (5-ALA) within adenine-functionalized supramolecular micelles (A-PPG), in order to achieve effective drug delivery combined with photo-chemotherapy. The resulting DOX/5-ALA-loaded micelles exhibited excellent light and pH-responsive behavior in aqueous solution and high drug-entrapment stability in serum-rich media. A short duration (1-2 min) of laser irradiation with visible light induced the dissociation of the DOX/5-ALA complexes within the micelles, which disrupted micellular stability and resulted in rapid, immediate release of the physically entrapped drug from the micelles. In addition, in vitro assays of cellular reactive oxygen species generation and cellular internalization confirmed the drug-loaded micelles exhibited significantly enhanced cellular uptake after visible light irradiation, and that the light-triggered disassembly of micellar structures rapidly increased the production of reactive oxygen species within the cells. Importantly, flow cytometric analysis demonstrated that laser irradiation of cancer cells incubated with DOX/5-ALA-loaded A-PPG micelles effectively induced apoptotic cell death via endocytosis. Thus, this newly developed supramolecular system may offer a potential route towards improving the efficacy of synergistic chemotherapeutic approaches for cancer.

ROS-initiated chemiluminescence-driven payload release from macrocycle-based Azo-containing polymer nanocapsules.

Reactive oxygen species (ROS) overproduction is involved in many pathological processes, particularly in inflammatory diseases. Therefore, ROS-responsive nanocarriers for specific drug release have been highly sought after. Herein we developed a ROS-responsive drug delivery system based on covalently self-assembled polymer nanocapsules (Azo-NCs) formed via crosslinking macrocyclic cucurbit[6]urils by a photo-sensitive azobenzene derivative (Azo). Luminol, a chemiluminescent molecule activatable by ROS, was co-loaded into Azo-NCs together with a therapeutic payload. When exposed to high ROS concentration that is typically encountered in inflammatory cells or tissues, the ROS-initiated blue chemiluminescence of luminol drives photoisomerization of the Azo groups within Azo-NCs, leading to Azo-NCs' surface transformation and distortion of the nanostructure, and subsequent payload release. As a proof-of-concept, ROS-responsive payload release from luminol-loaded Azo-NCs in inflammatory cells and zebrafish was demonstrated, showing promising anti-inflammatory effects in vitro and in vivo.

Cyanine Nanocage Activated by Near-IR Light for the Targeted Delivery of Cyclosporine A to Traumatic Brain Injury Sites.

More than 2.8 million annually in the United States are afflicted with some form of traumatic brain injury (TBI), where 75% of victims have a mild form of TBI (MTBI). TBI risk is higher for individuals engaging in physical activities or involved in accidents. Although MTBI may not be initially life-threatening, a large number of these victims can develop cognitive and physical dysfunctions. These late clinical sequelae have been attributed to the development of secondary injuries that can occur minutes to days after the initial impact. To minimize brain damage from TBI, it is critical to diagnose and treat patients within the first or "golden" hour after TBI. Although it would be very helpful to quickly determine the TBI locations in the brain and direct the treatment selectively to the affected sites, this remains a challenge. Herein, we disclose our novel strategy to target cyclosporine A (CsA) into TBI sites, without the need to locate the exact location of the TBI lesion. Our approach is based on TBI treatment with a cyanine dye nanocage attached to CsA, a known therapeutic agent for TBI that is associated with unacceptable toxicities. In its caged form, CsA remains inactive, while after near-IR light photoactivation, the resulting fragmentation of the cyanine nanocage leads to the selective release of CsA at the TBI sites.

Addressing the Biochemical Foundations of a Glucose-Based "Trojan Horse"-Strategy to Boron Neutron Capture Therapy: From Chemical Synthesis to In Vitro Assessment.

Boron neutron capture therapy (BNCT) for cancer is on the rise worldwide due to recent developments of in-hospital neutron accelerators which are expected to revolutionize patient treatments. There is an urgent need for improved boron delivery agents, and herein we have focused on studying the biochemical foundations upon which a successful GLUT1-targeting strategy to BNCT could be based. By combining synthesis and molecular modeling with affinity and cytotoxicity studies, we unravel the mechanisms behind the considerable potential of appropriately designed glucoconjugates as boron delivery agents for BNCT. In addition to addressing the biochemical premises of the approach in detail, we report on a hit glucoconjugate which displays good cytocompatibility, aqueous solubility, high transporter affinity, and, crucially, an exceptional boron delivery capacity in the in vitro assessment thereby pointing toward the significant potential embedded in this approach.