Mucin-mediated mucosal retention via end-terminal modified Pluronic F127-based hydrogel to increase drug accumulation in the lungs.

Noninvasive lung drug delivery is critical for treating respiratory diseases. Pluronic-based copolymers have been used as multifunctional materials for medical and biological applications. However, the Pluronic F127-based hydrogel is rapidly degraded, adversely affecting the mechanical stability for prolonged drug release. Therefore, this study designed two thermosensitive copolymers by modifying the Pluronic F127 terminal groups with carboxyl (ADF127) or amine groups (EDF127) to improve the viscosity and storage modulus of drug formulations. ß-alanine and ethylenediamine were conjugated at the terminal of Pluronic F127 using a two-step acetylation process, and the final copolymers were characterized using 1H nuclear magnetic resonance (1H NMR) and Fourier-transform infrared spectra. According to the 1H NMR spectra, Pluronic F127 was functionalized to form ADF127 and EDF127 with 85 % and 71 % functionalization degrees, respectively. Rheological studies revealed that the ADF127 (15 wt%) and EDF127 (15 wt%) viscosities increased from 1480 Pa.s (Pluronic F127) to 1700 Pa.s and 1800 Pa.s, respectively. Furthermore, the elastic modulus of ADF127 and EDF127 increased, compared with that of native Pluronic F127 with the addition of 5 % mucin, particularly for ADF127, thereby signifying the stronger adhesive nature of ADF127 and EDF127 with mucin. Additionally, ADF127 and EDF127 exhibited a decreased gelation temperature, decreasing from 33 °C (Pluronic F127 at 15 wt%) to 24 °C. Notably, the in vitro ADF127 and EDF127 drug release was prolonged (95 %; 48 h) by the hydrogel encapsulation of the liposome-Bdph combined with mucin, and the intermolecular hydrogen bonding between the mucin and the hydrogel increased the retention time and stiffness of the hydrogels. Furthermore, ADF127 and EDF127 incubated with NIH-3T3 cells exhibited biocompatibility within 2 mg/mL, compared with Pluronic F127. The nasal administration method was used to examine the biodistribution of the modified hydrogel carrying liposomes or exosomes with fluorescence using the IVIS system. Drug accumulation in the lungs decreased in the following order: ADF127 > EDF127 > liposomes or exosomes alone. These results indicated that the carboxyl group-modified Pluronic F127 enabled well-distributed drug accumulation in the lungs, which is beneficial for intranasal administration routes in treating diseases such as lung fibrosis.

Preconditioning of exosomes derived from human olfactory ensheathing cells improved motor coordination and balance in an SCA3/MJD mouse model: A new therapeutic approach.

Exosome therapy is a novel trend in regeneration medicine. However, identifying a suitable biomarker that can associate the therapeutic efficacy of exosomes with SCA3/MJD is essential. In this study, parental cells were preconditioned with butylidenephthalide (Bdph) for exosome preparation to evaluate the therapeutic effect of SCA3/MJD. The therapeutic agent hsa-miRNA-6780-5p was enriched up to 98-fold in exosomes derived from butylidenephthalide (Bdph)-preconditioned human olfactory ensheathing cells (hOECs) compared with that in naïve hOECs exosomes. The particle sizes of exosomes derived from naïve hOECs and those derived from hOECs preconditioned with Bdph were approximately 113.0 ± 3.5 nm and 128.9 ± 0.7 nm, respectively. A liposome system was used to demonstrate the role of hsa-miRNA-6780-5p, wherein hsa-miRNA-6780-5p was found to enhance autophagy and inhibit the expression of spinocerebellar ataxia type 3 (SCA3) disease proteins with the polyglutamine (polyQ) tract. Exosomes with enriched hsa-miRNA-6780-5p were further applied to HEK-293-84Q cells, leading to decreased expression of polyQ and increased autophagy. The results were reversed when 3MA, an autophagy inhibitor, was added to the cells treated with hsa-miRNA-6780-5p-enriched exosomes, indicating that the decreased polyQ expression was modulated via autophagy. SCA3 mice showed improved motor coordination behavior when they intracranially received exosomes enriched with hsa-miRNA-6780-5p. SCA3 mouse cerebellar tissues treated with hsa-miRNA-6780-5p-enriched exosomes showed decreased expression of polyQ and increased expression of LC3II/I, an autophagy marker. In conclusion, our findings can serve as a basis for developing an alternative therapeutic strategy for SCA3 disease treatment using miRNA-enriched exosomes derived from chemically preconditioned cells.

Eco-benign synthesis of nano­gold chitosan-bacterial cellulose in spent ground coffee kombucha consortium: Characterization, microbiome community, and biological performance.

Biomaterials that are mediocre for cell adhesion have been a concern for medical purposes. In this study, we fabricated nano­gold chitosan-bacterial cellulose (CBC-Au) via a facile in-situ method using spent ground coffee (SGC) in a kombucha consortium. The eco-benign synthesis of monodispersed gold nanoparticles (Au NPs) in modified bacterial cellulose (BC) was successfully achieved in the presence of chitosan (CHI) and a symbiotic culture of bacteria and yeast (SCOBY). The dominant microbiome community in SGC kombucha were Lactobacillaceae and Saccharomycetes. Chitosan-bacterial cellulose (CBC) and CBC-Au affected the microfibril networks in the nano cellulose structures and decreased the porosity. The modified BC maintained its crystallinity up to 80 % after incorporating CHI and Au NPs. Depth profiling using X-ray photoelectron spectroscopy (XPS) indicated that the Au NPs were distributed in the deeper layers of the scaffolds and a limited amount on the surface of the scaffold. Aspergillus niger fungal strains validated the biodegradability of each scaffold as a decomposer. Bacteriostatically CBC-Au showed better antimicrobial activity than BC, in line with the adhesion of NIH-3T3 fibroblast cells and red blood cells (RBCs), which displayed good biocompatibility performance, indicating its potential use as a medical scaffold.

Fabrication of Ag nanostar and PEI-based SERS substrate for sensitive and rapid detection of SO2: Application for detection of sulfite residues in beer.

Because of sulfite's potential toxicity, there is a growing concern about detecting and controlling its concentration in foods, alcoholic beverages, pharmaceuticals, and environmental samples to ensure public health. A branched polyethyleneimine-coated silver nano-star (AgNS@PEI) surface-enhanced Raman scattering (SERS) substrate was synthesized in this study for use as a sensitive, simple, rapid, stable, and reproducible non-destructible sulfite detection analytical technique. The seed morphology of the nano-star was created by using hydroxylamine (NH2OH) solution as a primary reducing agent, followed by a slow secondary reduction by trisodium citrate dihydrate (HOC(COONa)(CH2COONa)2 2H2O), resulting in the complete growth of the silver nano-star. For extra stability and selective absorption of sulfur dioxide from the headspace extraction of SO2 from sulfites, the nano-stars were thin coated with branched polyethyleneimine (b-PEI). The results showed that the thin-coated plasmonic substrates selectively absorb sulfur dioxide molecules, allowing sulfites in beer samples to be detected with a detection limit of 0.48 mg/L. Furthermore, the PEI-coated silver nano-star demonstrated increased stability and reproducibility, allowing for longer use of the substrate. Recovery experiments with recovery rates ranging from 95 to 112% and relative standard deviations ranging from 1.55 to 8.1% demonstrated that headspace extraction, selective SO2 absorption by the synthesized substrate, and subsequent SERS detections were reliable and valid for practical applications. Finally, this study developed an SO2-sensitive, selective, and robust Si@AgNS@PEI substrate for effective SERS detection and monitoring of sulfite levels in real-world environmental samples.

Hofmeister effect-based soaking strategy for gelatin hydrogels with adjustable gelation temperature, mechanical properties, and ionic conductivity.

As a natural polymer with good biocompatibility, gelatin hydrogel has been widely used in the field of biomedical science for a long time. However, the lack of suitable gelation temperature and mechanical properties often limit the clinical applicability in diverse and complex environments. Here, we proposed a strategy based on the Hofmeister effect that gelatin hydrogels were soaked in the appropriate concentration of sodium sulfate solution, and the change in molecular chain interactions mainly guided by kosmotropic ions resulted in a comprehensive adjustment of multiple properties. A series of gelatin hydrogels treated with different concentrations of the salt solution gave rise to microstructural changes, which brought a decrease in the number and size of pores, a wide range of gelation temperature from 32 °C to 46 °C, a stress enhancement of about 40 times stronger to 0.8345 MPa, a strain increase of about 7 times higher to 238.05 %, and a certain degree of electrical conductivity to be utilized for versatile applications. In this regard, for example, we prepared microneedles and obtained a remarkable compression (punctuation) strength of 0.661 N/needle, which was 55 times greater than those of untreated ones. Overall, by integrating various characterizations and suggesting the corresponding mechanism behind the phenomenon, this method provides a simpler and more convenient performance control procedure. This allowed us to easily modulate the properties of the hydrogel as per the intended purpose, revealing its vast potential applications such as smart sensors, electronic skin, and drug delivery.

Plasmonic nanoparticle-based surface-enhanced Raman spectroscopy-guided photothermal therapy: emerging cancer theranostics.

Optical imaging modalities have emerged as a keystone in oncological research, capable of providing molecular and cellular information on cancer with the advantage of being minimally invasive toward healthy tissues. Photothermal therapy (PTT) has shown great potential, with the exceptional advantages of high specificity and noninvasiveness. Combining surface-enhanced Raman spectroscopy (SERS)-based optical imaging with PTT has shown tremendous potential in cancer theranostics (therapeutics + diagnosis). This comprehensive review article provides up-to-date information by exploring recent works focused mainly on the development of plasmonic nanoparticles for medical applications using SERS-guided PTT, including the fundamental principles behind SERS and the plasmon heating effect for PTT.

Multifunctional thermosensitive hydrogel based on alginate and P(NIPAM-co-HEMIN) composites for accelerated diabetic wound healing.

Non-healing wounds in patients with diabetes are a concerning issue associated with amputation and a high mortality rate. These wounds are exacerbated by oxidative stress and microbial infections resulting from hyperglycemia. Therefore, advanced materials for repairing wound beds must be identified urgently. This paper introduces a topically applicable composite hydrogel with thermosensitive properties and presents the antibacterial and antioxidant activities in mice with diabetes-induced wounds. This composite is developed by combining poly N-isopropyl acrylamide (NIPAM)-copolymerized HEMIN (NIPAM-co-HEMIN) and amine-modified alginate (ALG-EDA) biomaterials, with Ag nanoparticles (AgNPs) incorporated into the system as an antibacterial agent. Results of antibacterial tests show that the p(NIPAM-co-HEMIN)/ALG-EDA/AgNP composite system is effective against E. coli and S. aureus. Additionally, the AgNP composite exhibits low cellular toxicity in NIH3T3 and CT-2A cell lines. The wounds in diabetic mice treated with the composite system healed in <12 days, and the composite system accelerated the healing process by increasing collagen synthesis. In conclusion, the biocomposite reported herein is highly promising for repairing diabetic skin wounds and treating infections caused by bacterial microbes.

Plasmonic surface-enhanced Raman scattering nano-substrates for detection of anionic environmental contaminants: Current progress and future perspectives.

Surface-enhanced Raman scattering spectroscopy (SERS) is a powerful technique of vibrational spectroscopy based on the inelastic scattering of incident photons by molecular species. It has unique properties such as ultra-sensitivity, selectivity, non-destructivity, speed, and fingerprinting properties for analytical and sensing applications. This enables SERS to be widely used in real-world sample analysis and basic plasmonic mechanistic studies. However, the desirable properties of SERS are compromised by the high cost and low reproducibility of the signals. The development of multifunctional, stable and reusable nano-engineered SERS substrates is a viable solution to circumvent these drawbacks. Recently, plasmonic SERS active nano-substrates with various morphologies have attracted the attention of researchers due to promising properties such as the formation of dense hot spots, additional stability, tunable and controlled morphology, and surface functionalization. This comprehensive review focused on the current advances in the field of SERS active nanosubstrates suitable for the detection and quantification of anionic environmental pollutants. The common fabrication methods, including the techniques for morphological adjustments and surface modification, substrate categories, and the design of nanotechnologically fabricated plasmonic SERS substrates for anion detection are systematically presented. Here, the need for the design, synthesis, and functionalization of SERS nano-substrates for anions of great environmental importance is explained in detail. In addition, the broad categories of SERS nano-substrates, namely colloid-based SERS substrates and solid-support SERS substrates are discussed. Moreover, a brief discussion of SERS detection of certain anionic pollutants in the environment is presented. Finally, the prospects in the fabrication and commercialization of pilot-scale handheld SERS sensors and the construction of smart nanosubstrates integrated with novel amplifying materials for the detection of anions of environmental and health concern are proposed.

Fabrication and characterization of hybrid eco-friendly high methoxyl pectin/gelatin/TiO2/curcumin (PGTC) nanocomposite biofilms for salmon fillet packaging.

Hybrid eco-friendly nanocomposite films were fabricated by blending high-methoxyl pectin, gelatin, TiO2, and curcumin through the solution casting method. Various concentrations (0-5 wt%) of TiO2 nanoparticles (TNPs) and curcumin as an organic filler were added to the blend solutions. A high TNP concentration affected the surface morphology, roughness, and compactness of the films. Additionally, 3D mapping revealed the nanoparticle distribution in the film layers. Moisture content, water solubility, and light transmittance reduced dramatically with increasing TNP content, in accordance with the water vapor and oxygen permeabilities. X-ray diffraction revealed that the films were semicrystalline nanocomposites, and the thermal properties of the films increased when 5 wt% of TNPs was incorporated into the blend solution. Fourier-transform infrared and Raman analyses revealed interactions among biopolymers, nanoparticles, and organic fillers through hydrogen bonding. The shelf life of fresh salmon fillets was prolonged to six days for all groups, revealed by total viable counts and psychrotrophic bacteria counts, and the pH of the salmon fillets could be extended until the sixth day for all groups. Biodegradation assays demonstrated a significant weight loss in the nanocomposite films. Therefore, a nanocomposite film with 5 wt% TNPs could potentially be cytotoxic to NIH 3T3 cells.

Antiblood Cell Adhesion of Mussel-Inspired Chondroitin Sulfate- and Caffeic Acid-Modified Polycarbonate Membranes.

We fabricated a mussel-inspired hemocompatible polycarbonate membrane (PC) modified by the cross-linking of chondroitin sulfate and caffeic acid polymer using CA-CS via a Schiff base and Michael addition reaction and named it CA-CS-PC. The as-fabricated CA-CS-PC membrane shows excellent hydrophilicity with a water contact angle of 0° and a negative surface charge with a zeta potential of -32 mV. The antiadhesion property of the CA-CS-modified PC membrane was investigated by enzyme-linked immunosorbent assay (ELISA), using human plasma protein fibrinogen adsorption studies, and proved to have excellent antiadhesion properties, because of the lower fibrinogen adsorption. In addition, the CA-CS-PC membrane also shows enhanced hemocompatibility. Finally, blood cell attachment tests of the CA-CS-PC membrane were observed by CLSM and SEM, and the obtained results proved that CA-CS-PC effectively resisted cell adhesion, such as platelets and leucocytes. Therefore, this work disclosed a new way to design a simple and versatile modification of the membrane surface by caffeic acid and chondroitin sulfate and apply it for cell adhesion.

Sustainable, biocompatible, and mass-producible superwetting water caltrop shell biochars for emulsion separations.

The separation of oily wastewater, specifically emulsions, is a crucial global issue. Possible strategies for the efficient separation of emulsified oil/water mixtures through sustainable and environmentally friendly materials have recently drawn considerable attention. In our study, we prepared superwetting water caltrop shell biochar (WCSB) via a top-lit-updraft carbonization procedure. The as-prepared WCSB was characterized by superhydrophilicity, underwater superoleophobicity, underoil superhydrophilicity, and underoil water adsorption ability. Because of its superwetting properties, WCSB was used for the separation of both surfactant-stabilized oil-in-water emulsions (SOIWEs) and surfactant-stabilized water-in-oil emulsions (SWIOEs) with very high fluxes (up to 74,700 and 241,000 L m-2 h-1 bar-1 for SOIWE and SWIOE, respectively). The separation performances were excellent, with oil contents in all SOIWE filtrates lower than 10 ppm and oil purities in all SWIOE filtrates higher than 99.99 wt%. Moreover, WCSB was applied to separate dye-spiked emulsions. Due to their high emulsion separation ability, sustainability, good biocompatibility, and ease of mass production, the as-prepared WCSBs have notable potential for utilitarian applications.

pH/redox-responsive core cross-linked based prodrug micelle for enhancing micellar stability and controlling delivery of chemo drugs: An effective combination drug delivery platform for cancer therapy.

Core-crosslinking of micelles (CCMs) appears to be a favorable strategy to enhance micellar stability and sustained release of the loaded drug. In this study, the DOX-conjugated pH-sensitive polymeric prodrug Methoxy Poly (ethylene oxide)-b-Poly (Aspartate-Hydrazide) (mPEG-P [Asp-(Hyd-DOX)] was created using ring-opening polymerization. To further enhance the micellar system, 3,3'-diselanediyldipropanoic acid (DSeDPA) was applied to link the hydrophobic segment via click reaction to form pH/redox-responsive CCMs. Dual anti-cancer drugs, DOX as a pro-drug and SN-38 as a targeting drug, were used to enhance inhibition. DLS confirmed that the non-cross-linked micelle (NCMs) showed a higher (96.43 nm) particle size compared to the CCMs (72.63 nm). Due to micellar shrinkage after crosslinking, CCMs displayed SN-38 drug loading (7.32 %) and encapsulation efficiency (86.23 %). The mPEG-P(Asp-Hyd) copolymer's in vitro cytotoxicity on HeLa and HaCaT cell lines found that 84.52 % of the cells are alive, and zebrafish (Danio rerio) embryos and larvae are highly biocompatible. The DOX/SN-38@CCMs had a sustained discharge profile in vitro, unlike the DOX/SN-38@NCMs. In DOX/SN-38@CCMs, HeLa cells were inhibited 50.90 % more than HaCaT (14.25 %) at the maximum drug dose (10 µg/mL). The CCMs successfully targeted and supplied DOX/SN-38 in HeLa cells rather than HaCaT cells, based on cellular uptake of 2D cell culture. CCMs, unlike NCMs, inhibit the growth of spheroids for extended periods of time due to the prolonged release of the loaded drug. Overall, CCMs are good-looking for use as regulated delivery of DOX/SN-38 in cancer cells because of all of these appealing characteristics.

PAMAM Dendritic Nanoparticle-Incorporated Hydrogel to Enhance the Immunogenic Cell Death and Immune Response of Immunochemotherapy.

The efficiency of chemotherapy is frequently affected by its multidrug resistance, immune suppression, and severe side effects. Its combination with immunotherapy to reverse immune suppression and enhance immunogenic cell death (ICD) has emerged as a new strategy to overcome the aforementioned issues. Herein, we construct a pH-responsive PAMAM dendritic nanocarrier-incorporated hydrogel for the co-delivery of immunochemotherapeutic drugs. The stepwise conjugation of moieties and drug load was confirmed by various techniques. In vitro experimental results demonstrated that PAMAM dendritic nanoparticles loaded with a combination of drugs exhibited spherical nanosized particles, facilitated the sustained release of drugs, enhanced cellular uptake, mitigated cell viability, and induced apoptosis. The incorporation of PAB-DOX/IND nanoparticles into thermosensitive hydrogels also revealed the formation of a gel state at a physiological temperature and further a robust sustained release of drugs at the tumor microenvironment. Local injection of this formulation into HeLa cell-grafted mice significantly suppressed tumor growth, induced immunogenic cell death-associated cytokines, reduced cancer cell proliferation, and triggered a CD8+ T-cell-mediated immune response without obvious systemic toxicity, which indicates a synergistic ICD effect and reverse of immunosuppression. Hence, the localized delivery of immunochemotherapeutic drugs by a PAMAM dendritic nanoparticle-incorporated hydrogel could provide a promising strategy to enhance antitumor activity in cancer therapy.

Poly(vinylidene fluoride) Intestinal Sleeve Implants for the Treatment of Obesity and Type 2 Diabetes.

Currently, treatment of diabetes and associated obesity involves Roux-en-Y gastric bypass or sleeve gastrectomy to reduce the absorption of nutrients from the intestine to achieve blood glucose control. However, the surgical procedure and subsequent recovery are physically and psychologically burdensome for patients, with possible side effects, so alternative treatments are being developed. In this study, two methods, solution casting and machine direction orientation (MDO), were used to prepare intestinal implants made of poly(vinylidene fluoride) (PVDF) film and implant them into the duodenum of type 2 diabetic rats for the treatment of obesity and blood glucose control. The PVDF film obtained by the MDO process was characterized by FT-IR, Raman spectroscopy, XRD and piezoelectricity tests, which showed higher composition of ß crystalline phase and better elongation and mechanical strength in specific directions. Therefore, the material was finally tested on rats after it was proven to be non-toxic by biological toxicity tests. The PVDF was implanted into alloxan-induced diabetic rats, which were used as a model of impaired insulin secretion due to pancreatic beta cell destruction rather than obesity-induced diabetes, and rats were tracked for 24 days, showing significantly improved body weight and blood glucose levels. As an alternative therapeutic option, intestinal sleeve implant showed future potential for application.

Fluorine-Free Superhydrophobic Covalent-Organic-Polymer Nanosheet Coating for Selective Dye and Emulsion Separation.

Covalent organic polymer nanosheets (COPNs) endowed with porous networks and large surface areas in their structures offer great advantages over other materials in addressing environmental problems. In this study, fluorine-free superhydrophobic COPNs were designed and applied to selective dye absorption. Notably, COPNs selectively adsorb dyes with a high hydrophobic index (HI) and reject low HI dyes with maximum adsorption capacities of 361 and 263 mg/g for crystal violet and methylene blue, respectively. The adsorption isotherm model showed that the COPNs follow the Langmuir adsorption isotherm model and pseudo-second-order kinetics. Next, we explored the superhydrophobicity of the COPNs by in situ fabrication with melamine sponge (COPNs-MS), which incorporates the superhydrophobicity of COPNs [water contact angle (WCA) of >150°] with the structure and flexibility of the MS skeleton. The COPNs-MS shows various oil-adsorbing properties with good adsorption capacity (from 60 to 120 g/g) and also effectively separates various surfactant-stabilized emulsions with a separation efficiency of over 99%. The as-fabricated COPNs-MS retains its superhydrophobicity in various solvents and hazardous conditions (WCA ≥ 150°) and exhibits good flame retardancy and excellent compression properties with excellent antifouling property due to the superhydrophobic COPN coating. Furthermore, COPNs-MS also demonstrates excellent recyclability because the strong COPN coating in the MS skeleton retains its hydrophobicity. Therefore, our fluorine-free superhydrophobic COPNs are not only capable of selective dye adsorption but also exhibit very good oil adsorption and surfactant-stabilized emulsion separation performance.

Protein-assisted biomimetic synthesis of nanoscale gadolinium-integrated polypyrrole for synergetic and ultrasensitive electrochemical assays of nicardipine in biological samples.

Electrically conductive polymer nanomaterials signify a promising class of sensing platforms in the field of electrochemistry, but their applications as electrocatalysts are commonly limited by their poor colloidal stability in aqueous media and large particle sizes. Inspired by biomineralization approaches for integrating nanoscale materials, herein, a gadolinium (Gd)-integrated polypyrrole (PPy) electrocatalyst (namely, BSA@PPy-Gd) was successfully prepared by choosing bovine serum albumin (BSA) as a stabilizer for biomimetic mineralization and polymerization in a "one-step" manner. BSA@PPy-Gd possesses outstanding water dispersibility, nanoscale morphology, and improved electrical conductivity. The electrocatalytic competency of the electrochemical (EC) sensing platform fabricated for the sensitive detection of nicardipine (NCD) was assessed. The synergy of remarkable conductivity, superior active surface area, and electrostatic interactions stimulated by the combination of BSA with the NH group of PPy on BSA@PPy-Gd and Gd increases the fast electron transfer at the analyte-electrode junction. The fabricated EC sensor, BSA@PPy-Gd/glassy carbon electrode (GCE), exhibits a current intensity greater than that of PPy/GCE, BSA/GCE, and bare GCE in terms of peak height at a pH of 7.0 in phosphate buffer solution. The newly fabricated EC sensing platform shows excellent electrocatalytic activities for the electroreduction of NCD in terms of a low detection limit (2 nM), good sensitivity, linear dynamic detection ranges (0.01-575 µM), operational stability, and repeatability and was also tested on rat and human serum specimens.

Combination of ovalbumin-coated iron oxide nanoparticles and poly(amidoamine) dendrimer-cisplatin nanocomplex for enhanced anticancer efficacy.

Enhancement of drug efficacy is essential in cancer treatment. The immune stimulator ovalbumin (Ova)-coated citric acid (AC-)-stabilized iron oxide nanoparticles (AC-IO-Ova NPs) and enhanced permeability and retention (EPR)-based tumor targeted 4.5 generation poly(amidoamine) dendrimer(4.5GDP)-cisplatin (Cis-pt) nanocomplex (NC) (4.5GDP-Cis-pt NC) were used for enhanced anticancer efficiency. The formations of 4.5GDP-Cis-pt NC, AC-IO, and AC-IO-Ova NPs were examined via FTIR spectroscopy, X-ray diffraction, Raman spectroscopy, and X-ray photoelectron spectroscopy. The conjugation of Cis-pt with 4.5GDP was confirmed using carbon NMR spectroscopy. The tumor-specific 4.5GDP-Cis-pt NC provided 45%and 28% cumulative cisplatin release in 72 h at pH 6.5 and 7.4, respectively. A significant immune response with high TNF-α and IL-6 cytokine secretion was confirmed for the co-incubation of AC-IO-Ova with RAW 264.7 or HaCaT cells. AC-IO-Ova NPs were biocompatible with different cell lines, even at a high concentration (200 µg mL-1). However, AC-IO-Ova NPs mixed with 4.5GDP-Cis-pt NC (Cis-pt at 15 µg mL-1) significantly increased the cytotoxicity against the cancer cells in a dose-dependent manner with the increasing AC-IO-Ova NPs concentrations. The increased anticancer effects may be attributed to the generation of reactive oxygen species (ROS). Moreover, AC-IO-Ova NPs might assist the efficiency of anticancer cells, inducing an innate immune response via M1 macrophage polarization. We provide a novel synergistic chemoimmunotherapeutic strategy to enhance the anticancer efficacy of cisplatin via a chemotherapeutic agent 4.5GDP-Cis-pt NC and induce proinflammatory cytokines stimulating innate immunity through AC-IO-Ova NPs against tumors.

Preparation of physically crosslinked polyelectrolyte Gelatin-Tannic acid-κ-Carrageenan (GTC) microparticles as hemostatic agents.

In humans, excessive bleeding during civilian accidents, and surgery account for 40% of the mortality worldwide. Hence, the development of biocompatible hemostatic materials useful for rapid hemorrhage control has become a fundamental research problem in the biomedicine community. In this study, we prepared biocompatible gelatin-tannic acid-κ-carrageenan (GTC) microparticles using a facile Tween 80 stabilized water-in-oil (W/O) emulsion method for rapid hemostasis. The formation of GTC microparticles occurs via polyelectrolyte interactions between gelatin and k-carrageenan as well as hydrogen bonding from tannic acid. In addition, the GTC microparticles formulated in our study showed high water adsorption ability with a low volume-swelling ratio for a particle size of 46 µm. In addition, the GTC microparticles displayed >80% biocompatibility in NIH 3T3 cells and <5% hemocompatibility in hemolysis ratio tests. Notably, the GTC microparticles induced rapid blood clotting in 50 s and blood loss of approximately 46 mg in the femoral artery of BALB/c female mice with a 100% survival rate that was significantly better than the control group (blood clot time:250 s; blood loss: 259 mg). Thus, the findings from our study collectively suggest that GTC microparticles may play a promising clinical role in medical applications to tackle hemorrhage control.

Recent developments in selenium-containing polymeric micelles: prospective stimuli, drug-release behaviors, and intrinsic anticancer activity.

Selenium is capable of forming a dynamic covalent bond with itself and other elements and can undergo metathesis and regeneration reactions under optimum conditions. Its dynamic nature endows selenium-containing polymers with striking sensitivity towards some environmental alterations. In the past decade, several selenium-containing polymers were synthesized and used for the preparation of oxidation-, reduction-, and radiation-responsive nanocarriers. Recently, thioredoxin reductase, sonication, and osmotic pressure triggered the cleavage of Se-Se bonds and swelling or disassembly of nanostructures. Moreover, some selenium-containing nanocarriers form oxidation products such as seleninic acids and acrylates with inherent anticancer activities. Thus, selenium-containing polymers hold promise for the fabrication of ultrasensitive and multifunctional nanocarriers of radiotherapeutic, chemotherapeutic, and immunotherapeutic significance. Herein, we discuss the most recent developments in selenium-containing polymeric micelles in light of their architecture, multiple stimuli-responsive properties, emerging immunomodulatory activities, and future perspectives in the delivery and controlled release of anticancer agents.