A molybdenum oxide-based degradable nanosheet for combined chemo-photothermal therapy to improve tumor immunosuppression and suppress distant tumors and lung metastases.

Molybdenum oxide (MoOx) nanosheets have drawn increasing attention for minimally invasive cancer treatments but still face great challenges, including complex modifications and the lack of efficient accumulation in tumor. In this work, a novel multifunctional degradable FA-BSA-PEG/MoOx nanosheet was fabricated (LA-PEG and FA-BSA dual modified MoOx): the synergistic effect of PEG and BSA endows the nanosheet with excellent stability and compatibility; the FA, a targeting ligand, facilitates the accumulation of nanosheets in the tumor. In addition, DTX, a model drug for breast cancer treatment, was loaded (76.49%, 1.5 times the carrier weight) in the nanosheets for in vitro and in vivo antitumor evaluation. The results revealed that the FA-BSA-PEG/MoOx@DTX nanosheets combined photothermal and chemotherapy could not only inhibit the primary tumor growth but also suppress the distant tumor growth (inhibition rate: 51.7%) and lung metastasis (inhibition rate: 93.6%), which is far more effective compared to the commercial Taxotere®. Exploration of the molecular mechanism showed that in vivo immune response induced an increase in positive immune responders, suppressed negative immune suppressors, and established an inflammatory tumor immune environment, which co-contributes towards effective suppression of tumor and lung metastasis. Our experiments demonstrated that this novel multifunctional nanosheet is a promising platform for combined chemo-photothermal therapy.

Synthesis, characterization, and evaluation of curcumin-loaded endodontic reparative material.

Curcumin (CUR) is an ancient therapeutic agent with remarkable antimicrobial and anti-inflammatory properties. The purpose of the current study was to synthesize and evaluate a curcumin-based reparative endodontic material to reduce infection and inflammation besides the induction of mineralization during the healing of the dentin-pulp complex. Poly-ɛ-caprolactone (PCL)/gelatin (Gel)/CUR scaffold was synthesized and assessed by scanning electron microscopy, Fourier transform infrared spectroscopy, and thermo-gravimetric analysis (TGA). Agar diffusion test was performed against E. coli, A. baumannii, P. aeruginosa, S. aureus, E. faecalis, and S. mutans. Moreover, proliferative, antioxidative, anti-inflammatory, and calcification properties of these scaffolds on human dental pulp stem cells (hDPSCs) were evaluated. The results showed that PCL/Gel/CUR scaffold had antibacterial effects. Also, these CUR-based scaffolds had significant inhibitory effects on the expression of tumor necrosis factor α and DCF from inflamed hDPSCs (p < 0.05). Moreover, the induction of mineralization in hDPSCs significantly increased after seeding on CUR-based scaffolds (p < 0.05). Based on these findings, the investigated CUR-loaded material was fabricated successfully and provided an appropriate structure for the attachment and proliferation of hDPSCs. It was found that these scaffolds had antimicrobial, antioxidant, and anti-inflammatory characteristics and could induce mineralization in hDPSCs, which is essential for healing and repairing the injured dentin-pulp complex.

An overview of chitosan and its application in infectious diseases.

Infectious diseases, such as the coronavirus disease-19, SARS virus, Ebola virus, and AIDS, threaten the health of human beings globally. New viruses, drug-resistant bacteria, and fungi continue to challenge the human efficacious drug bank. Researchers have developed a variety of new antiviral and antibacterial drugs in response to the infectious disease crisis. Meanwhile, the development of functional materials has also improved therapeutic outcomes. As a natural material, chitosan possesses good biocompatibility, bioactivity, and biosafety. It has been proven that the cooperation between chitosan and traditional medicine greatly improves the ability of anti-infection. This review summarized the application and design considerations of chitosan-composed systems for the treatment of infectious diseases, looking forward to providing the idea of infectious disease therapy.

Scalable dextran-polypyrrole nano-assemblies with photothermal/photoacoustic dual capabilities and enhanced biocompatibility.

Polypyrroles have shown great potential in photoacoustic imaging and photothermal therapy owing to its excellent photothermal conversion capabilities. However, the synthesis of polypyrrole-based nano-assemblies which have colloidal stability in biological buffers requires a number of steps, including the polymerization of pyrrole monomers, self-assembly of polypyrrole-based copolymers, and even an additional step to increase the biocompatibility of the nano-assemblies. Herein, a "polymerization/assembly" two-in-one synthesis is proposed for the first time to achieve the one-step synthesis of a new family of polypyrrole-based nano-assemblies, dextran-polypyrrole nano-assemblies (Dex-PPy NAs), under ambient conditions and in aqueous media. In addition, the approach employs tetravalent cerium ions as initiators which can initiate the polymerization of pyrrole monomers through the initiation of free radicals from dextran molecular chains. The resultant Dex-PPy NAs have a photothermal conversion efficiency reaching as high as 41 % and an excellent photostability. More importantly, the NAs with controllable nanoscale dimensions display no signs of cytotoxicity in both in vitro and in vivo studies owing to their biocompatible dextran "shell". An in vivo study further confirmed that the Dex-PPy NAs have excellent real-time photoacoustic imaging and photothermal therapy capabilities for malignant tumors. Therefore, this study represents an important step towards the scalable synthesis of polypyrrole-based nano-assemblies with photothermal/photoacoustic dual capabilities and enhanced biocompatibility.

In Vitro and In Vivo Evaluations of Mesoporous Iron Particles for Iron Bioavailability.

Chronic renal failure involving hemodialysis results in blood loss during filtration. Iron deficiency and iron deficiency anemia can result. A compensatory increase in iron dosage has many side effects including discomfort. Elemental iron is a highly-pure iron source, which reduces the frequency of dosages; the solubility decreases with increased particle size or pore size. In this study, synthesized mesoporous iron particles (MIPs) were used to relieve iron deficiency anemia. Their bioavailability was measured in vitro by a Caco-2 cell model and in vivo in iron-deficient rats. In vitro bioavailability of MIPs was examined by measuring ferritin content in the Caco-2 cell model. Iron uptake of MIPs was significantly higher than commercial iron particles, which were less porous. In vivo bioavailability of MIPs was examined by measuring body weight gain and red blood cell-related parameters, compared with the bioavailability of standard drug ferrous sulfate in iron-deficient anemic rats. Finally, average hemoglobin content and hemoglobin regeneration efficiency were significantly higher in anemic rats supplemented with commercial iron particles, compared to anemic controls. In the 28-day oral toxicity test, MIPs were not significantly toxic to rat physiology or tissue histopathology. Thus, MIPs may allow effective recovery of hemoglobin in iron deficiency anemia.

Facile preparation of a Ca(ii) carboxymethyl cellulose complex with enhanced calcium bioavailability for treatment of osteoporosis.

At present, though calcium (Ca) reagents with high calcium contents are widely synthesized, their wide application is limited due to their low absorption rates and poor bioavailability. Here we use a carboxymethyl cellulose (CMC) derivative with high water solubility and biocompatibility as a ligand to bind Ca2+. The resulting CaCMC complex exhibits remarkable solubility and absorbability under both basic and acidic conditions as well as in stomach mimicking and the gastrointestinal tract. Importantly, this Ca reagent shows high in vivo calcium bioavailability. Data from osteoporosis mouse models show that the CaCMC complex is superior to calcium carbonate in the treatment of osteoporosis. Therefore, the resulting CaCMC complex is used as a new, highly effective and desirable Ca supplement for daily life and clinical applications.

A murine model of cutaneous aspergillosis for evaluation of biomaterials-based local delivery therapies.

Cutaneous fungal infection is a challenging condition to treat that primarily afflicts immunocompromised patients. Local antifungal therapy may permit the delivery of high concentrations of antifungals directly to wounds while minimizing systemic toxicities. However, the field currently lacks suitable in vivo models. Therefore, a large cutaneous wound was created in immunosuppressed mice and inoculated with Aspergillus fumigatus. We fabricated biodegradable polymer microparticles (MPs) that were capable of locally delivering antifungal and characterized in vitro release kinetics. We compared wound bed size, fungal burden, and histological presence of fungi in mice treated with antifungal-loaded MPs. Mice with a cutaneous defect but no infection, mice with infected cutaneous defect but no treatment, and infected mice treated with blank MPs were used as controls. Infection of large wounds inhibited healing and resulted in tissue invasion in an inoculum-dependent manner. MPs were capable of releasing antifungals at concentrations above A. fumigatus Minimum Inhibitory Concentration (MIC) for at least 6 days. Wounds treated with MPs had significantly decreased size compared with no treatment (64.2% vs. 19.4% wound reduction, p = 0.002) and were not significantly different from uninfected controls (64.2% vs. 58.1%, p = 0.497). This murine model may serve to better understand cutaneous fungal infection and evaluate local biomaterials-based therapies. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1867-1874, 2019.

Photothermal-Controlled Generation of Alkyl Radical from Organic Nanoparticles for Tumor Treatment.

The therapeutic properties of light are well known for photodynamic or photothermal therapy, which could cause irreversible photodamage to tumor tissues. Although photodynamic therapy (PDT) has been proved in the clinic, the efficacy is not satisfactory because of complicated tumor microenvironments. For example, the hypoxia in solid tumor has a negative effect on the generation of singlet oxygen. To address the hypoxia issues in PDT, leveraging alkyl radical is an available option due to the oxygen-independent feature. In this work, a new kind of organic nanoparticles (tripolyphosphate (TPP)-NN NPs) from porphyrin and radical initiator is developed. Under near-infrared light irradiation, TPP-NN NPs will split and release alkyl radical, which could induce obvious cytotoxicity both in normal and hypoxia environment. The photothermal-controlled generation of alkyl radical could significantly inhibit the growth of cervical cancer and show ignorable systemic toxicity. This activatable radical therapy opens up new possibilities for the application of PDT in hypoxia condition.

[Assessment of changes in the lesions sizes and the incidence of complete epithelialization during the treatment of diabetic foot syndrome over a period of 4 weeks (multicenter study)]. / Otsenka dinamiki ploshchadi rany i chastoty sluchaev polnoi epitelizatsii pri lechenii sindroma diabeticheskoi stopy (rezul'taty mnogotsentrovogo issledovaniya).

AIM: To assess the effectiveness of the collagen biomaterial in treatment process in patients with DFS. MATERIAL AND METHODS: 71 patients 30-80 y.o. with diabetic foot syndrome of varying severity were included in prospective multicenter study. Patients were randomized into two homogeneous groups: control group (n=35) - standard therapy, other 36 patients (main group) were additionally treated with medical device (MD) Collost in accordance with the instructions for use. RESULTS: Biomaterial Collost using in complex treatment of diabetic foot syndrome resulted in more rapid and effective healing of the ulcer. The treatment success increased from 43% to 72%. Complete epithelialization was achieved by 2.6 times more rapidly in conjunction with reduction the incidence of unsuccessful treatment results by 4.1 times.

Engulfment of ceramic particles by fibroblasts does not alter cell behavior.

Despite many studies, the impact of ceramic particles on cell behavior remains unclear. The aim of the present study was to investigate the effects of nano-sized ceramic particles on fibroblastic cells. Fibroblasts (dermal fibroblasts freshly isolated from skin samples and WI26 fibroblastic cells) were cultured in a monolayer in the presence of alumina or cerium-zirconia particles (≈50 nm diameter) at two concentrations (100 or 500 µg ml-1). Fluorescent alumina particles were also used. The following properties were analyzed: cell morphology, cytoplasmic ceramic incorporation (using confocal and transmission electron microscopy) and migration (using a silicon insert). Sedimentation field-flow fractionation (SdFFF) was also used to evaluate the rate of incorporation of ceramic particles into the cells. Finally, after treatment with various concentrations of ceramic particles, fibroblasts were also included in a collagen type I lattice constituting a dermal equivalent (DE), and the collagen lattice retraction and cell proliferation were evaluated. In monolayer conditions, the presence of both alumina and cerium-zirconia ceramic particles did not cause any deleterious effects on cultured cells (dermal fibroblast and WI26 cells) and cell fate was not affected in any way by the presence of ceramic particles in the cytoplasm. Confocal (using fluorescent alumina particles) and electron microscopy (using both alumina and cerium-zirconia particles) showed that ceramic particles were internalized in the WI26 cells. Using fluorescent membrane labeling and fluorescent alumina particles, a membrane was observed around the particle-containing vesicles present in the cytoplasm. Electron microscopy on WI26 cells showed the presence of a classical bilayer membrane around the ceramic particles. Interestingly, SdFFF confirmed that some dermal fibroblasts contained many alumina ceramic particles while others contained very few; in WI26 cells, the uptake of alumina ceramic was more homogeneous. In DE, collagen lattice retraction and cell proliferation were unchanged when WI26 fibroblastic cells contained alumina or cerium-zirconia ceramic particles. Our data suggest that ceramic particles are internalized in the cells by endocytosis. The presence of ceramic particles in the cytoplasm has no affect on cell behavior, confirming the excellent biocompatibility of this material and anticipating a minimal harmful effect of potential wear debris.

In Vitro Release Kinetics of Microencapsulated Materials and the Effect of the Food Matrix.

Many biomaterials are encapsulated to preserve their health-promoting properties and promote targeted delivery. Numerous papers have been published about extraction and purification methods, encapsulation techniques, and release properties of encapsulated biomaterials. Despite the abundant information, the food applications of encapsulated materials are currently limited. One approach to increase the food applications is to investigate the mathematical aspects of release behavior and the effect of the food matrix. Such information is useful in evaluating suitable food matrices and predicting the extent of bioavailability of the biomaterial. This review aims to discuss the kinetic models of release, current efforts to promote sustained release, and food matrices currently used in in vitro investigations. Information from pharmaceutical studies is integrated and reviewed to determine possible food applications. Future research on microencapsulated biomaterials conducted along these aspects may hopefully hasten nutraceutical applications.

Biodegradable Photonic Melanoidin for Theranostic Applications.

Light-absorbing nanoparticles for localized heat generation in tissues have various biomedical applications in diagnostic imaging, surgery, and therapies. Although numerous plasmonic and carbon-based nanoparticles with strong optical absorption have been developed, their clearance, potential cytotoxicity, and long-term safety issues remain unresolved. Here, we show that "generally regarded as safe (GRAS)" melanoidins prepared from glucose and amino acid offer a high light-to-heat conversion efficiency, biocompatibility, biodegradability, nonmutagenicity, and efficient renal clearance, as well as a low cost for synthesis. We exhibit a wide range of biomedical photonic applications of melanoidins, including in vivo photoacoustic mapping of sentinel lymph nodes, photoacoustic tracking of gastrointestinal tracts, photothermal cancer therapy, and photothermal lipolysis. The biodegradation rate and renal clearance of melanoidins are controllable by design. Our results confirm the feasibility of biodegradable melanoidins for various photonic applications to theranostic nanomedicines.

Optimization of Surface Coating on Small Pd Nanosheets for in Vivo near-Infrared Photothermal Therapy of Tumor.

Palladium nanosheets with strong near-infrared absorption have been recently demonstrated as promising photothermal agents for photothermal therapy (PTT) of cancers. However, systematic assessments of their potential risks and impacts to biological systems have not been fully explored yet. In this work, we carefully investigate how surface coatings affect the in vivo behaviors of small Pd nanosheets (Pd NSs). Several biocompatible molecules such as carboxymethyl chitosan (CMC), PEG-NH2, PEG-SH, and dihydrolipoic acid-zwitterion (DHLA-ZW) were used to coat Pd NSs. The blood circulation half-lives, biodistribution, potential toxicity, clearance, and photothermal effect of different surface-coated Pd NSs in mice after intravenous injection were compared. PEG-SH-coated Pd NSs (Pd-HS-PEG) were found to have ultralong blood circulation half-life and show high uptake in the tumor. We then carry out the in vivo photothermal therapeutic studies on the Pd-HS-PEG conjugate and revealed its outstanding efficacy in in vivo photothermal therapy of cancers. Our results highlight the importance of surface coatings to the in vivo behaviors of nanomaterials and can provide guidelines to the future design of Pd NSs bioconjugates for other in vivo applications.

An effective approach to reduce inflammation and stenosis in carotid artery: polypyrrole nanoparticle-based photothermal therapy.

Photothermal therapy (PTT), as a promising treatment for tumours, has rarely been reported for application in artery restenosis, which is a common complication of endovascular management due to enduring chronic inflammation and abnormal cell proliferation. In our study, biodegradable polypyrrole nanoparticles (PPy-NPs) were synthesized and characterized, including their size distribution, UV-vis-NIR absorbance, molar extinction coefficients, and photothermal properties. We then verified that PPy-NP incubation followed by 915 nm near-infrared (NIR) laser irradiation could effectively ablate inflammatory macrophages in vitro, leading to significant cell apoptosis and cell death. Further, it was found that a combination of local PPy-NP injection with 915 nm NIR laser irradiation could significantly alleviate arterial inflammation by eliminating infiltrating macrophages and further ameliorating artery stenosis in an ApoE(-/-) mouse model, without showing any obvious toxic side effects. Thus, we propose that PTT based on PPy-NPs as photothermal agents and a 915 nm NIR laser as a power source can serve as a new effective treatment for reducing inflammation and stenosis formation in inflamed arteries after endovascular management.

Recent advances in characterization of nonviral vectors for delivery of nucleic acids: impact on their biological performance.

INTRODUCTION: Nucleic acid delivery is a complex process that requires transport across numerous extracellular and intracellular barriers, whose impact is often neglected during optimization studies. As such, the development of nonviral vectors for efficient delivery would benefit from an understanding of how these barriers relate to the physicochemical properties of lipoplexes and polyplexes. AREAS COVERED: This review focuses on the evaluation of parameters associated with barriers to delivery such as blood and immune cells compatibility which, as a collective, may serve as a useful prescreening tool for the advancement of nonviral vectors in vivo. An outline of the most relevant rationally developed polyplexes and lipoplexes for clinical application is also given. EXPERT OPINION: The evaluation of scientifically recognized parameters enabled the identification of systemic delivered nonviral vectors' behavior while in blood as one of the key determinants of vectors function and activity both in vitro and in vivo. This multiparametric approach complements the use of in vitro efficacy results alone for prescreening and improves in vitro-in vivo translation by minimizing false negatives. Further, it can aid in the identification of meaningful structure-function-activity relationships, improve the in vitro screening process of nonviral vectors before in vivo use and facilitate the future development of potent and safe nonviral vectors.

Plasmonic nanodiamonds: targeted core-shell type nanoparticles for cancer cell thermoablation.

Targeted biocompatible nanostructures with controlled plasmonic and morphological parameters are promising materials for cancer treatment based on selective thermal ablation of cells. Here, core-shell plasmonic nanodiamonds consisting of a silica-encapsulated diamond nanocrystal coated in a gold shell are designed and synthesized. The architecture of particles is analyzed and confirmed in detail using electron tomography. The particles are biocompatibilized using a PEG polymer terminated with bioorthogonally reactive alkyne groups. Azide-modified transferrin is attached to these particles, and their high colloidal stability and successful targeting to cancer cells overexpressing the transferrin receptor are demonstrated. The particles are nontoxic to the cells and they are readily internalized upon binding to the transferrin receptor. The high plasmonic cross section of the particles in the near-infrared region is utilized to quantitatively ablate the cancer cells with a short, one-minute irradiation by a pulse 750-nm laser.

Curcumin-loaded PLGA nanoparticles conjugated with anti- P-glycoprotein antibody to overcome multidrug resistance.

BACKGROUND: The encapsulation of curcumin (Cur) in polylactic-co-glycolic acid (PLGA) nanoparticles (Cur- NPs) was designed to improve its solubility and stability. Conjugation of the Cur-NPs with anti-P-glycoprotein (P-gp) antibody (Cur-NPs-APgp) may increase their targeting to P-gp, which is highly expressed in multidrug- resistance (MDR) cancer cells. This study determined whether Cur-NPs-APgp could overcome MDR in a human cervical cancer model (KB-V1 cells) in vitro and in vivo. MATERIALS AND METHODS: First, we determined the MDR- reversing property of Cur in P-gp-overexpressing KB-V1 cells in vitro and in vivo. Cur-NPs and Cur-NPs-APgp, in the range 150-180 nm, were constructed and subjected to an in vivo pharmacokinetic study compared with Cur. The in vitro and in vivo MDR-reversing properties of Cur-NPs and Cur-NPs-APgp were then investigated. Moreover, the stability of the NPs was determined in various solutions. RESULTS: The combined treatment of paclitaxel (PTX) with Cur dramatically decreased cell viability and tumor growth compared to PTX treatment alone. After intravenous injection, Cur-NPs-APgp and Cur-NPs could be detected in the serum up to 60 and 120 min later, respectively, whereas Cur was not detected after 30 min. Pretreatment with Cur-NPs-APgp, but not with NPs or Cur-NPs, could enhance PTX sensitivity both in vitro and in vivo. The constructed NPs remained a consistent size, proving their stability in various solutions. CONCLUSIONS: Our functional Cur-NPs-APgp may be a suitable candidate for application in a drug delivery system for overcoming drug resistance. The further development of Cur-NPs-APgp may be beneficial to cancer patients by leading to its use as either as a MDR modulator or as an anticancer drug.

PEG-modified carbon nanotubes in biomedicine: current status and challenges ahead.

Since their discovery at the end of the previous millennium, carbon nanotubes (CNTs) have been the object of thousands of papers describing their applications in fields ranging from physics to electronics, photonics, chemistry, biology, and medicine. The development of chemical approaches to modify their graphitic sidewalls enabled the generation of poly(ethylene glycol) (PEG)-modified CNTs and their exploration in multiple biomedical applications. Studies at the cellular and organism level revealed that PEG-modified CNTs have favorable pharmacokinetic and toxicology profiles. Recently, PEG-modified CNTs have been successfully tested in preclinical studies in the fields of oncology, neurology, vaccination, and imaging, suggesting that they are well suited for the generation of novel multifunctional nanodrugs. Here we will review published data about the application of PEG-modified CNTs as in vitro and in vivo therapeutic and imaging tools and describe what is known about the interaction between PEG-modified CNTs and biological systems. Although several pieces of the puzzle are still missing, we will also attempt to formulate a preliminary structure-function model for PEG-modified CNT cellular trafficking, disposition, and side effects.

Oxide and hybrid nanostructures for therapeutic applications.

The research on biomedical applications of nanoparticles has seen an upsurge in recent years due to their unique capabilities in treatment of ailments. Though there are ample reviews on the advances of nanoparticles right from their fabrication to applications, comparatively fewer reviews are available for the nanostructured materials particularly on oxides and hybrids. These materials possess unique physicochemical properties with an ability to get functionalized at molecular and cellular level for biochemical interactions. Keeping the enormosity of the nanostructures in mind, we intend to cover only the recent and most noteworthy developments in this area. We, particularly emphasize on iron oxide and its derivatives, zinc oxides, layered double hydroxides, silica and binary/ternary metal oxides and their applications in the area of therapeutics. This review also focuses on the designing of biodegradable and biocompatible nanocarriers and critical issues related to their therapeutic applications. Several representative examples discuss targeting strategies and stimuli responsive nanocarriers and their therapeutics.

Chitosan effect on dental enamel de-remineralization: an in vitro evaluation.

OBJECTIVES: The aim of this work was to evaluate the in vitro effect of chitosan (concentration and time of action) treatment on enamel de-remineralization behavior upon a pH cycling assay. METHODS: Different group of human tooth samples were exposed to de-remineralizing solutions of controlled pH using a random experimental design. Microhardness and phosphorus chemical analysis were employed to evaluate the loss of phosphorus from the samples. Optical coherence tomography (OCT) images were obtained for selected specimens in order to evaluate the degree of penetration of chitosan into enamel. RESULTS: Vickers microhardness results were higher for samples treated with chitosan for concentration between 2.5mg/mL and 5.0mg/mL and time of action between 60s and 90 s. A maximum inhibition of mineral loss of 81% was obtained. Chemical analysis indicated lower net pohosphorus loss (net P loss) for samples treated with chitosan. Best results were obtained in the same conditions found out with microhardness measurements. Chitosan had little effect on the remineralization process. OCT results indicated a correlation of chitosan penetration with chitosan concentration. For chitosan concentrations of 2.5 g/mL and 5.0 g/mL the penetration was up to the dentin-enamel junction. CONCLUSIONS: Chitosan interferes with the process of demineralization of the tooth enamel inhibiting the release of phosphorus in this laboratory study. Demineralization is influenced by the concentration and exposure time of the biopolymer to the enamel. Microhardness measurements may be used as an indication of mineral loss from tooth enamel. Additionally, OCT images support the idea that chitosan may act as a barrier against acid penetration, contributing to its demineralization inhibition.