Membrane cholesterol enrichment and folic acid functionalization lead to increased accumulation of erythrocyte-derived optical nano-constructs within the ovarian intraperitoneal tumor implants in mice.

Cytoreductive surgery remains as the gold standard to treat ovarian cancer, but with limited efficacy since not all tumors can be intraoperatively visualized for resection. We have engineered erythrocyte-derived nano-constructs that encapsulate the near infrared (NIR) fluorophore, indocyanine green (ICG), as optical probes for NIR fluorescence imaging of ovarian tumors. Herein, we have enriched the membrane of these nano-constructs with cholesterol, and functionalized their surface with folic acid (FA) to target the folate receptor-α. Using a mouse model, we show that the average fraction of the injected dose per tumor mass for nano-constructs with both membrane cholesterol enrichment and FA functionalization was ~ sixfold higher than non-encapsulated ICG, ~ twofold higher than nano-constructs enriched with cholesterol alone, and 33 % higher than nano-constructs with only FA functionalization at 24-h post-injection. These results suggest that erythrocyte-derived nano-constructs containing both cholesterol and FA present a platform for improved fluorescence imaging of ovarian tumors.

Near-infrared light activatable niosomes loaded with indocyanine green and plasmonic gold nanorods for theranostic applications.

Light-mediated theranostic platforms involve the use of agents (small molecules/nanomaterials), which can absorb light to produce either heat or reactive chemical species (RCS) and emit fluorescence. Such platforms are advantageous in the field of personalized medicine, as they provide enhanced diagnostic capabilities, improved therapeutic efficiencies, and can also simultaneously monitor the treatment outcomes using imaging modalities. Specifically, agents absorbing near-infrared (NIR) light can provide minimal scattering, low autofluorescence, superior spatio-temporal resolution, and deeper tissue penetration depths. Gold nanorods (GNR) and indocyanine green (ICG) are two agents known to absorb light in the NIR region. GNR can provide tunable plasmonic properties, while ICG is an FDA-approved NIR fluorophore. However, the use of ICG and GNR suffers from various limitations, such as photobleaching, non-specificity, toxicity, and aggregation in solution. To overcome these limitations, herein, we report on NIR light-activatable niosomes loaded with GNR and ICG for cancer theranostic applications. Both agents were encapsulated into non-ionic surfactant-based biocompatible niosomes to form ICG-GNR@Nio with superior loading efficiencies and enhanced properties. ICG-GNR@Nio offers excellent storage stability, photostability, elevated temperature rise and generation of reactive oxygen species (ROS) upon 1064 nm laser irradiation. Subsequently, the enhanced phototherapeutic capabilities mediated by ICG-GNR@Nio were validated in the in vitro cellular experiments. Overall, ICG-GNR@Nio-based theranostic platforms can provide a significant benchmark in the improved diagnosis and therapeutic capabilities for biomedical clinicians to tackle various diseases.

Facile Synthesis of Multifunctional Carbon Dots Derived from Camel Milk for Mn7+ Sensing and Antiamyloid and Anticancer Activities.

Carbon dots (CDs) are promising biocompatible fluorescent nanoparticles mainly used in bioimaging, drug delivery, sensing, therapeutics, and various other applications. The utilization of natural sources and green synthetic approaches is resulting in highly biocompatible and nontoxic nanoparticles. Herein, we report an unprecedented facile and green synthesis of highly luminescent carbon dots derived from camel milk (CM) for sensing manganese (Mn7+) ions and for identifying the anticancer potential and antiamyloid activity against α-synuclein amyloids. α-Synuclein amyloid formation due to protein misfolding (genetic and environmental factors) has gained significant attention due to its association with Parkinson's disease and other synucleinopathies. The as-synthesized CM-CDs possess an average hydrodynamic diameter ranging from 3 to 15 nm and also exhibit strong photoluminescence (PL) emission in the blue region. The CM-CDs possess good water dispersibility, stable fluorescence under different physical states, and outstanding photostability. Moreover, the CM-CDs are validated as an efficient sensor for the detection of Mn7+ ions in DI water and in metal ion-polluted tap water. In addition, the CM-CDs have demonstrated a very good quantum yield (QY) of 24.6% and a limit of detection (LOD) of 0.58 µM for Mn7+ ions with no incubation time. Consequently, the exceptional properties of CM-CDs make them highly suitable for a diverse array of biomedical applications.

A Label-Free and Ultrasensitive Prussian Blue-Based Dipstick Sensor for Bacterial and Biofilm Detection.

Water and food contamination has become the major contributor to infections and deaths. However, rapid and sensitive bacterial detection still remains an unmet demand that has attracted widespread attention. Often water and food samples are sent out for laboratory testing to detect the presence of contamination, which is time-consuming and laborious. Herein, we have developed a highly sensitive, tenable, affordable, and robust (STAR) paper-based colorimetric dipstick sensor based on the principle of Prussian blue (PB) synthesis as an indicator of bacterial contamination. In the presence of bacteria, it leads to the formation of PB, a dye that acts as a colorimetric indicator. The intensity of the PB is the direct measure of the degree of contamination. The fabrication of the STAR dipstick sensor involves a simple and cost-effective process. The STAR dipstick sensor is ultrasensitive and can detect up to 101 CFU/mL of bacteria within minutes of contact with the test sample. The STAR dipstick sensor is fabricated using biodegradable components, which is speculated to facilitate quick and environmentally friendly degradation after each use. The sensor has been validated for its properties and capabilities at different pH to detect both Gram-positive and Gram-negative bacterial strains in real-time samples. The stability and degradation were also monitored. Comprehensively, the proposed STAR dipstick sensor can serve as a point-of-care device to detect bacterial contamination in a swift and sensitive manner.

Cellular metabolic activity and electrochemical stability assay of embedded oxidoreductase enzyme confined in the nanospace of a framework exoskeleton.

In the present study, we sought to reveal how embedding oxidoreductase enzymes in a metal-organic framework influences restoring the biofunctionality when encapsulated within zeolitic imidazolate framework (ZIF-8 and ZIF-90), wherein these biocomposites were explored for their cellular metabolic activity using the (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) (MTT) assay on A549 lung cancer cells and NIH3T3 (mouse fibroblasts) cells. We chose two biocomposites, namely catalase-encapsulated ZIF-8 and ZIF-90, wherein the enzyme was encapsulated at varied loadings through a rapid self-triggered nucleation around the protein surfaces of the enzyme. Interestingly, this embedding pattern of catalase in both ZIF-8 and ZIF-90 depended on the surface chemistry of the enzyme. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy analysis revealed the stability of the encapsulated enzyme in the nanospace of the ZIF-8 and ZIF-90 frameworks. Investigation of the cellular metabolic activity by the MTT assay of Cat@ZIF-8 and Cat@ZIF-90 on the lung cancer cell A549 showed cell viability enhancement in the case of Cat@ZIF-8 at a higher percentage compared to that of Cat@ZIF-90. A similar metabolic activity assay was performed with the internalization of Cat@ZIF-90 for NIH3T3 (mouse fibroblasts) cells. The revealed difference between the MOF compounds was due to the nano-confinement effect in ZIF-8 compared to ZIF-90, which can accelerate the utilization in cellar metabolic activity.

Effects of the aspect ratio of plasmonic gold nanorods on the inhibition of lysozyme amyloid formation.

Amyloid formation due to altered protein folding and aggregation has gained significant attention due to its association with neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and systemic lysozyme amyloidosis. Amyloids are characterized by parallel and anti-parallel cross-ß-strands arranged to form stacks of sheets that provide stability and rigidity to the amyloid core. The prototypic protein Hen Egg White Lysozyme (HEWL) has been extensively used to understand protein hydrolysis, fragmentation, folding, misfolding, and amyloid formation. In the present study, we have examined the efficacy of plasmonic gold nanorods (GNRs) as an anti-amyloid agent against HEWL amyloids. Our results reveal that (i) the amyloid inhibition by plasmonic GNRs is dependent on their aspect ratio, (ii) the large aspect ratio GNRs ameliorate amyloid assembly completely, and (iii) GNRs interfere at several stages along the lysozyme fibril-formation pathway and block the conversion of monomeric and oligomeric intermediates into mature fibrils. Using a multi-parametric approach, we demonstrate that GNRs drive HEWL into off-pathway and amyloid-incompetent forms. To establish GNRs as generic amyloid inhibitors, we extended our studies to another archetypal protein, Bovine Serum Albumin (BSA), and observed similar results of GNRs inhibiting BSA aggregation. We believe that our results will pave the way for the potential use of GNRs with current therapeutics to reduce the burden of amyloid-related diseases.

Optical Characteristics of Indocyanine Green J-Aggregates Induced by Cisplatin for Phototheranostic Applications.

The development of an optical system for combinatorial theranostics is of significant interest. Clinical translation of such theranostic agents need to cross several barriers. Herein, we have developed a facile method for the preparation of J-aggregates using FDA approved agents, namely, NIR fluorophore indocyanine green (ICG) and a chemotherapeutic drug, cisplatin (CDDP), which induces ICG to form indocyanine green J-aggregates (IJAs). The formation of IJAs has been characterized by the formation of a new absorption peak centered at ∼896 nm. The existing methods to synthesize IJAs have used several harsh reaction conditions, such as elevated temperatures, for a prolonged time duration (∼60 days). To the best of our knowledge, for the first time, we have reported the formation of IJAs assisted by CDDP at 37 °C temperature within 12 h. The presence of CDDP in ICG favors IJA formation and thereby reduces the harshness of the reaction conditions in the conventionally followed protocols. Moreover, the presence of CDDP can facilitate photoactivated combinatorial therapy. The as synthesized IJA optical system has superior properties to those of free ICG, in terms of diagnostic and therapeutic capabilities (being activatable at ∼896 nm wavelength, which can achieve deeper tissue penetration) and excellent optical and storage stability. The facile synthesis proposed along with CDDP incorporation makes the optical system a clinically relevant one-component theranostic agent.

Erythrocyte-Derived Nanoparticles with Folate Functionalization for Near Infrared Pulsed Laser-Mediated Photo-Chemotherapy of Tumors.

Despite its common side effects and varying degrees of therapeutic success, chemotherapy remains the gold standard method for treatment of cancer. Towards developing a new therapeutic approach, we have engineered nanoparticles derived from erythrocytes that contain indocyanine green as a photo-activated agent that enables near infrared photothermal heating, and doxorubicin hydrochloride (DOX) as a chemotherapeutic drug. We hypothesize that milliseconds pulsed laser irradiation results in rapid heating and photo-triggered release of DOX, providing a dual photo-chemo therapeutic mechanism for tumor destruction. Additionally, the surface of the nanoparticles is functionalized with folate to target the folate receptor-α on tumor cells to further enhance the therapeutic efficacy. Using non-contract infrared radiometry and absorption spectroscopy, we have characterized the photothermal response and photostability of the nanoparticles to pulsed laser irradiation. Our in vitro studies show that these nanoparticles can mediate photo-chemo killing of SKOV3 ovarian cancer cells when activated by pulsed laser irradiation. We further demonstrate that this dual photo-chemo therapeutic approach is effective in reducing the volume of tumor implants in mice and elicits an apoptotic response. This treatment modality presents a promising approach in destruction of small tumor nodules.

Recent Progress in Red Blood Cells-Derived Particles as Novel Bioinspired Drug Delivery Systems: Challenges and Strategies for Clinical Translation.

Red Blood Cells (RBCs)-derived particles are an emerging group of novel drug delivery systems. The natural attributes of RBCs make them potential candidates for use as a drug carrier or nanoparticle camouflaging material as they are innately biocompatible. RBCs have been studied for multiple decades in drug delivery applications but their evolution in the clinical arena are considerably slower. They have been garnering attention for the unique capability of conserving their membrane proteins post fabrication that help them to stay non-immunogenic in the biological environment prolonging their circulation time and improving therapeutic efficiency. In this review, we discuss about the synthesis, significance, and various biomedical applications of the above-mentioned classes of engineered RBCs. This article is focused on the current state of clinical translation and the analysis of the hindrances associated with the transition from lab to clinic applications.

Membrane Cholesterol Enrichment of Red Blood Cell-Derived Microparticles Results in Prolonged Circulation.

Particles fabricated from red blood cells (RBCs) can serve as vehicles for delivery of various biomedical cargos. Flipping of phosphatidylserine (PS) from the inner to the outer membrane leaflet normally occurs during the fabrication of such particles. PS externalization is a signal for phagocytic removal of the particles from circulation. Herein, we demonstrate that membrane cholesterol enrichment can mitigate the outward display of PS on microparticles engineered from RBCs. Our in-vitro results show that the phagocytic uptake of cholesterol-enriched particles by murine macrophages takes place at a lowered rate, resulting in reduced uptake as compared to RBC-derived particles without cholesterol enrichment. When administered via tail-vein injection into healthy mice, the percent of injected dose (ID) per gram of extracted blood for cholesterol-enriched particles was ∼1.5 and 1.8 times higher than the particles without cholesterol enrichment at 4 and 24 h, respectively. At 24 h, ∼43% ID/g of the particles without cholesterol enrichment was eliminated or metabolized while ∼94% ID/g of the cholesterol-enriched particles were still retained in the body. These results indicate that membrane cholesterol enrichment is an effective method to reduce PS externalization on the surface of RBC-derived particles and increase their longevity in circulation.

Multifunctional CuO/Cu2O Truncated Nanocubes as Trimodal Image-Guided Near-Infrared-III Photothermal Agents to Combat Multi-Drug-Resistant Lung Carcinoma.

Despite the development of various therapeutic modalities to tackle cancer, multidrug resistance (MDR) and incomplete destruction of deep tissue-buried tumors remain as long-standing challenges responsible for tumor recurrence and low survival rates. In addition to the MDR and deep tissue photoactivation problems, most primary tumors metastasize to the lungs and lymph nodes to form secondary tumors. Therefore, it leaves a great challenge to develop theranostic approaches to combat both MDR and deep tissue photoactivation problems. Herein, we develop a versatile plasmonic CuO/Cu2O truncated nanocube-based theranostic nanomedicine to act as a triple modal near-infrared fluorescence (NIRF) imaging agent in the biological window II (1000-1500 nm)/photoacoustic imaging (PAI)/T1-weighted magnetic resonance (MR) imaging agents, sensitize the formation of singlet oxygen (1O2) to exert nanomaterial-mediated photodynamic therapeutic (NIR-II NmPDT), and absorb long NIR light (i.e., 1550 nm) in the biological window III (1500-1700 nm) to exert nanomaterial-mediated photothermal therapeutic (NIR-III NmPTT) effects for the effective destruction of multi-drug-resistant lung tumors. We found that H69AR lung cancer cells do not create drug resistance toward plasmonic CuO/Cu2O TNCs-based nanomedicines.

Recent advances in near infrared light responsive multi-functional nanostructures for phototheranostic applications.

Light-based theranostics have become indispensable tools in the field of cancer nanomedicine. Specifically, near infrared (NIR) light mediated imaging and therapy of deeply seated tumors using a single multi-functional nanoplatform have gained significant attention. To this end, several multi-functional nanomaterials have been utilized to tackle cancer and thereby achieve significant outcomes. The present review mainly focuses on the recent advances in the development of NIR light activatable multi-functional materials such as small molecules, quantum dots, and metallic nanostructures for the diagnosis and treatment of deeply seated tumors. The need for improved disease detection and enhanced treatment options, together with realistic considerations for clinically translatable nanomaterials will be the key driving factors for theranostic agent research in the near future. NIR-light mediated cancer imaging and therapeutic approaches offer several advantages in terms of minimal invasiveness, deeper tissue penetration, spatiotemporal resolution, and molecular specificities. Herein, we have reviewed the recent developments in NIR light responsive multi-functional nanostructures for phototheranostic applications in cancer therapy.

Near Infrared Fluorescence Imaging of Intraperitoneal Ovarian Tumors in Mice Using Erythrocyte-Derived Optical Nanoparticles and Spatially-Modulated Illumination.

Ovarian cancer is the deadliest gynecological cancer. Cytoreductive surgery to remove primary and intraperitoneal tumor deposits remains as the standard therapeutic approach. However, lack of an intraoperative image-guided approach to enable the visualization of all tumors can result in incomplete cytoreduction and recurrence. We engineered nano-sized particles derived from erythrocytes that encapsulate the near infrared (NIR) fluorochrome, indocyanine green, as potential imaging probes for tumor visualization during cytoreductive surgery. Herein, we present the first demonstration of the use of these nanoparticles in conjunction with spatially-modulated illumination (SMI), at spatial frequencies in the range of 0-0.5 mm-1, to fluorescently image intraperitoneal ovarian tumors in mice. Results of our animal studies suggest that the nanoparticles accumulated at higher levels within tumors 24 h post-intraperitoneal injection as compared to various other organs. We demonstrate that, under the imaging specifications reported here, use of these nanoparticles in conjunction with SMI enhances the fluorescence image contrast between intraperitoneal tumors and liver, and between intraperitoneal tumors and spleen by nearly 2.1, and 3.0 times, respectively, at the spatial frequency of 0.2 mm-1 as compared to the contrast values at spatially-uniform (non-modulated) illumination. These results suggest that the combination of erythrocyte-derived NIR nanoparticles and structured illumination provides a promising approach for intraoperative fluorescence imaging of ovarian tumor nodules at enhanced contrast.

Phototheranostics Using Erythrocyte-Based Particles.

There has been a recent increase in the development of delivery systems based on red blood cells (RBCs) for light-mediated imaging and therapeutic applications. These constructs are able to take advantage of the immune evasion properties of the RBC, while the addition of an optical cargo allows the particles to be activated by light for a number of promising applications. Here, we review some of the common fabrication methods to engineer these constructs. We also present some of the current light-based applications with potential for clinical translation, and offer some insight into future directions in this exciting field.

Virus-Mimicking Nanoparticles for Targeted Near Infrared Fluorescence Imaging of Intraperitoneal Ovarian Tumors in Mice.

Ovarian cancer is the most lethal malignancy affecting the female reproductive system. Identification and removal of all ovarian intraperitoneal tumor deposits during the intraoperative surgery is important towards preventing cancer recurrence and ultimately improving patient survival. Herein, we investigate the effectiveness of virus mimicking nanoparticles, derived from genome-depleted plant-infecting brome mosaic virus, and doped with near infrared (NIR) brominated cyanine dye BrCy106-NHS, for targeted NIR fluorescence imaging of intraperitoneal ovarian tumors. We refer to these nanoparticles as optical viral ghosts (OVGs). We functionalized the OVGs with antibodies against HER2 receptor, a biomarker over-expressed in ovarian cancers. We injected functionalized OVGs, non-functionalized OVGs, and non-encapsulated BrCy106-NHS intravenously in mice implanted with ovarian intraperitoneal tumors. Tumors were extracted at 2, 6, and 24 h post-injection, and quantitatively analyzed using NIR fluorescence imaging. Fluorescence emission from tumors associated with the injection of the functionalized OVGs continued to increase between 2 and 24 h post-injection. At 24 h timepoint, the average spectrally-integrated fluorescence emission from homogenized tumors containing functionalized-OVGs was about 3.5 and 19.5 times higher than those containing non-functionalized OVGs or non-encapsulated BrCy106-NHS, respectively. Similarly, by using the functionalized-OVGs, the imaging signal-to-noise ratio at 24 h timepoint was enhanced by approximately threefold and sevenfold as compared to non-functionalized OVGs and the non-encapsulated dye, respectively. These functionalized virus-mimicking NIR nano-constructs could potentially be used for intraoperative visualization of ovarian tumors implants.

Acute Immune Response of Micro- and Nanosized Erythrocyte-Derived Optical Particles in Healthy Mice.

Erythrocyte-derived particles activated by near-infrared (NIR) light present a platform for various phototheranostic applications. We have engineered such a platform with indocyanine green as the NIR-activated agent. A particular feature of these particles is that their diameters can be tuned from micro- to nanoscale, providing a potential capability for broad clinical utility ranging from vascular to cancer-related applications. An important issue related to clinical translation of these particles is their immunogenic effects. Herein, we have evaluated the early-induced innate immune response of these particles in healthy Swiss Webster mice following tail vein injection by measurements of specific cytokines in blood serum, the liver, and the spleen following euthanasia. In particular, we have investigated the effects of particle size and relative dose, time-dependent cytokine response for up to 6 h postinjection, functionalization of the nanosized particles with folate or Herceptin, and dual injections of the particles 1 week apart. Mean concentrations of interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, and monocyte chemoattractant protein (MCP)-1 in response to injection of microsized particles at the investigated relative doses were significantly lower than the corresponding mean concentrations induced by lipopolysaccharide (positive control) at 2 h. All investigated doses of the nanosized particles induced significantly higher concentrations of MCP-1 in the liver and the spleen as compared to phosphate buffer saline (PBS) (negative control) at 2 h. In response to micro- and nanosized particles at the highest investigated dose, there were significantly higher levels of TNF-α in blood serum at 2 and 6 h postinjection as compared to the levels associated with PBS treatment at these times. Whereas the mean concentration of TNF-α in the liver significantly increased between 2 and 6 h postinjection in response to the injection of the microsized particles, it was significantly reduced during this time interval in response to the injection of the nanosized particles. In general, functionalization of the nanosized particles was associated with a reduction of IL-6 and MCP-1 in blood serum, the liver, and the spleen, and TNF-α in blood serum. With the exception of IL-10 in the spleen in response to nanosized particles, the second injection of micro- or nanosized particles did not lead to significantly higher concentrations of other cytokines at the investigated dose as compared to a single injection.

Recent Advances of Polyaniline-Based Biomaterials for Phototherapeutic Treatments of Tumors and Bacterial Infections.

Conventional treatments fail to completely eradicate tumor or bacterial infections due to their inherent shortcomings. In recent years, photothermal therapy (PTT) has emerged as an attractive treatment modality that relies on the absorption of photothermal agents (PTAs) at a specific wavelength, thereby transforming the excitation light energy into heat. The advantages of PTT are its high efficacy, specificity, and minimal damage to normal tissues. To this end, various inorganic nanomaterials such as gold nanostructures, carbon nanostructures, and transition metal dichalcogenides have been extensively explored for PTT applications. Subsequently, the focus has shifted to the development of polymeric PTAs, owing to their unique properties such as biodegradability, biocompatibility, non-immunogenicity, and low toxicity when compared to inorganic PTAs. Among various organic PTAs, polyaniline (PANI) is one of the best-known and earliest-reported organic PTAs. Hence, in this review, we cover the recent advances and progress of PANI-based biomaterials for PTT application in tumors and bacterial infections. The future prospects in this exciting area are also addressed.

RBC-Derived Optical Nanoparticles Remain Stable After a Freeze-Thaw Cycle.

Nanosized carriers engineered from red blood cells (RBCs) provide a means for delivering various cargos, including drugs, biologics, and imaging agents. We have engineered nanosized particles from RBCs, doped with the near-infrared (NIR) fluorochrome, indocyanine green (ICG). An important issue related to clinical translation of RBC-derived nanocarriers, including these NIR nanoparticles, is their stability postfabrication. Freezing may provide a method for long-term storage of these and other RBC-derived nanoparticles. Herein, we have investigated the physical and optical stability of these particles in response to a single freeze-thaw cycle. Nanoparticles were frozen to -20 °C, stored frozen for up to 8 weeks, and then thawed at room temperature. Our results show that the hydrodynamic diameter, zeta potential, optical density, and NIR fluorescence emission of these nanoparticles are retained following the freeze-thaw cycle. The ability of these nanoparticles in NIR fluorescence imaging of ovarian cancer cells, as well as their biodistribution in reticuloendothelial organs of healthy Swiss Webster mice after the freeze-thaw cycle is similar to that for freshly prepared nanoparticles. These results indicate that a single cycle of freezing the RBC-derived nanoparticles to -20 °C followed by thawing at room temperature is an effective method to retain the physical and optical characteristics of the nanoparticles, and their interactions with biological systems without the need for use of cryoprotectants.

Photosensitized reactive chlorine species-mediated therapeutic destruction of drug-resistant bacteria using plasmonic core-shell Ag@AgCl nanocubes as an external nanomedicine.

Due to the rapid growth of drug-resistant bacterial infections, there is an urgent need to develop innovative antimicrobial strategies to conquer the bacterial antibiotic resistance problems. Although a few nanomaterial-based antimicrobial strategies have been developed, the sensitized formation of cytotoxic reactive chlorine species (RCS), including chlorine gas and chlorine free radicals, by photo-activatable plasmonic nanoparticles for evading drug-resistant bacterial infections has not yet been reported. To address this challenge, herein, we report the synthesis of an unprecedented plasmonic core-shell Ag@AgCl nanocrystal through an in situ oxidation route for the photo-induced generation of highly cytotoxic RCS. We present the detailed in vitro and in vivo investigations of visible light activated Ag@AgCl nanostructure-mediated evasion of drug-resistant bacteria. In particular, the in vivo results demonstrate the complete reepithelialization of the methicillin-resistant Staphylococcus aureus (MRSA) infected wounds on skin upon phototherapeutic treatment mediated Ag@AgCl NCs. To the best of our knowledge, this is the first unique example of using Ag@AgCl NCs as an external nanomedicine for photo-induced generation of RCS to mediate effective killing of both Gram-positive and Gram-negative drug resistance bacteria and healing of the subcutaneous abscesses in an in vivo mouse model.

Preparation, Cytotoxicity, and In Vitro Bioimaging of Water Soluble and Highly Fluorescent Palladium Nanoclusters.

Fluorescent probes offer great potential to identify and treat surgical tumors by clinicians. To this end, several molecular probes were examined as in vitro and in vivo bioimaging probes. However, due to their ultra-low extinction coefficients as well as photobleaching problems, conventional molecular probes limit its practical utility. To address the above mentioned challenges, metal nanoclusters (MNCs) can serve as an excellent alternative with many unique features such as higher molar extinction coefficients/light absorbing capabilities, good photostability and appreciable fluorescence quantum yields. Herein, we reported a green synthesis of water soluble palladium nanoclusters (Pd NCs) and characterized them by using various spectroscopic and microscopic characterization techniques. These nanoclusters showed excellent photophysical properties with the characteristic emission peak centered at 500 nm under 420 nm photoexcitation wavelength. In vitro cytotoxicity studies in human cervical cancer cells (HeLa) cells reveal that Pd NCs exhibited good biocompatibility with an IC50 value of >100 µg/mL and also showed excellent co-localization and distribution throughout the cytoplasm region with a significant fraction translocating into cell nucleus. We foresee that Pd NCs will carry huge potential to serve as a new generation bioimaging nanoprobe owing to its smaller size, minimal cytotoxicity, nucleus translocation capability and good cell labelling properties.