Co-Assembly of Cancer Drugs with Cyclo-HH Peptides: Insights from Simulations and Experiments.

Peptide-based nanomaterials can serve as promising drug delivery agents, facilitating the release of active pharmaceutical ingredients while reducing the risk of adverse reactions. We previously demonstrated that Cyclo-Histidine-Histidine (Cyclo-HH), co-assembled with cancer drug Epirubicin, zinc, and nitrate ions, can constitute an attractive drug delivery system, combining drug self-encapsulation, enhanced fluorescence, and the ability to transport the drug into cells. Here, we investigated both computationally and experimentally whether Cyclo-HH could co-assemble, in the presence of zinc and nitrate ions, with other cancer drugs with different physicochemical properties. Our studies indicated that Methotrexate, in addition to Epirubicin and its epimer Doxorubicin, and to a lesser extent Mitomycin-C and 5-Fluorouracil, have the capacity to co-assemble with Cyclo-HH, zinc, and nitrate ions, while a significantly lower propensity was observed for Cisplatin. Epirubicin, Doxorubicin, and Methorexate showed improved drug encapsulation and drug release properties, compared to Mitomycin-C and 5-Fluorouracil. We demonstrated the biocompatibility of the co-assembled systems, as well as their ability to intracellularly release the drugs, particularly for Epirubicin, Doxorubicin, and Methorexate. Zinc and nitrate were shown to be important in the co-assembly, coordinating with drugs and/or Cyclo-HH, thereby enabling drug-peptide as well as drug-drug interactions in successfully formed nanocarriers. The insights could be used in the future design of advanced cancer therapeutic systems with improved properties.

Peptide Self-Assembled Nanocarriers for Cancer Drug Delivery.

The design of novel cancer drug nanocarriers is critical in the framework of cancer therapeutics. Nanomaterials are gaining increased interest as cancer drug delivery systems. Self-assembling peptides constitute an emerging novel class of highly attractive nanomaterials with highly promising applications in drug delivery, as they can be used to facilitate drug release and/or stability while reducing side effects. Here, we provide a perspective on peptide self-assembled nanocarriers for cancer drug delivery and highlight the aspects of metal coordination, structure stabilization, and cyclization, as well as minimalism. We review particular challenges in nanomedicine design criteria and, finally, provide future perspectives on addressing a portion of the challenges via self-assembling peptide systems. We consider that the intrinsic advantages of such systems, along with the increasing progress in computational and experimental approaches for their study and design, could possibly lead to novel classes of single or multicomponent systems incorporating such materials for cancer drug delivery.

Synthesis of Doped/Hybrid Carbon Dots and Their Biomedical Application.

Carbon dots (CDs) are a novel type of carbon-based nanomaterial that has gained considerable attention for their unique optical properties, including tunable fluorescence, stability against photobleaching and photoblinking, and strong fluorescence, which is attributed to a large number of organic functional groups (amino groups, hydroxyl, ketonic, ester, and carboxyl groups, etc.). In addition, they also demonstrate high stability and electron mobility. This article reviews the topic of doped CDs with organic and inorganic atoms and molecules. Such doping leads to their functionalization to obtain desired physical and chemical properties for biomedical applications. We have mainly highlighted modification techniques, including doping, polymer capping, surface functionalization, nanocomposite and core-shell structures, which are aimed at their applications to the biomedical field, such as bioimaging, bio-sensor applications, neuron tissue engineering, drug delivery and cancer therapy. Finally, we discuss the key challenges to be addressed, the future directions of research, and the possibilities of a complete hybrid format of CD-based materials.

Exploring the Effect of Iron Metal-Organic Framework Particles in Polylactic Acid Membranes for the Azeotropic Separation of Organic/Organic Mixtures by Pervaporation.

A microporous carboxylate metal-organic framework MIL-100 Fe was prepared as submicron particles by microwave-assisted hydrothermal synthesis (Fe-MOF-MW). This product was explored, for the first time, for the preparation of polylactic acid (PLA) mixed matrix membranes. The produced MOF was characterised by powder X-ray diffraction (PXRD), environmental scanning electron microscopy (ESEM) as well as by thermogravimetric analysis (TGA) and nitrogen adsorption/desorption. The effect of different Fe-MOF-MW concentrations (0.1 and 0.5 wt%) on the membrane properties and performance were evaluated. These membranes were used in the pervaporation process for the separation of methanol/methyl tert-butyl-ether mixtures at the azeotropic point. The influence of the feed temperature and vacuum pressure on the membrane performance was evaluated and the results were compared with PLA pristine membranes. Moreover, the produced membranes have been characterised in terms of morphology, MOF dispersion in the polymeric membrane matrix, wettability, thickness, mechanical resistance and swelling propensity. The presence of Fe-MOF-MW was found to have a beneficial effect in improving the selectivity of mixed matrix membranes towards methanol at both concentrations. The highest selectivity was obtained for the PLA membranes embedded with 0.5 wt% of Fe-MOF-MW and tested at the temperature of 25 °C and vacuum pressure of 0.09 mbar.

AS101-Loaded PLGA-PEG Nanoparticles for Autoimmune Regulation and Chemosensitization.

The in vivo delivery of therapeutic nanoparticles (NPs) represents a potentially powerful tool that can significantly alter the biological effects of pharmaceutically active compounds. Here, we report on sensitization of tumors to chemotherapy by ammonium trichloro(dioxoethylene-o,o')tellurate (AS101) encapsulated in NPs, termed AS101-NPs, developed as a composite with the biocompatible and biodegradable copolymer of poly(d,l-lactic-co-glycolic acid)-block-poly(ethylene glycol) (PLGA-b-PEG). AS101 is a potent immunomodulating agent (both in vitro and in vivo) currently undergoing phase II clinical trials for antitumor activity and sensitization of tumors to chemotherapy. Approaches that can control the pharmacokinetic parameters to regulate its clearance from the administered drug delivery system and minimize side effects are of prodigious importance. A strategy to synthesize AS101-NPs by nanoprecipitation is presented, along with their physical characterization. The influence of AS101 encapsulation on its properties was evaluated in vivo. The AS101-NPs demonstrated a significantly enhanced peritoneal macrophage count compared with AS101 administered in vivo at a conventional dosage in mouse models. Moreover, AS101 inhibited B16 melanoma lung metastasis in mice when given intraperitoneally, before or after tumor cell inoculation. A bell-shaped dose-response was observed. The frequency of AS101 administration appears to be an important factor for achieving an optimal antimetastatic effect.

Fluorescent metal-doped carbon dots for neuronal manipulations.

There is a growing need for biocompatible nanocomposites that may efficiently interact with biological tissues through multiple modalities. Carbon dots (CDs) could serve as biocompatible fluorescence nanomaterials for targeted tissue/cell imaging. Important goals toward this end are to enhance the fluorescence quantum yields of the CDs and to increase their targetability to cells. Here, sonochemistry was used to develop a one-pot synthesis of CDs, including metal-doped CDs (M@CDs), demonstrating how various experimental parameters, such as sonication time, temperature, and power of sonication affect the size of the CDs (2-10 nm) and their fluorescence properties. The highest measured quantum yield of emission was ∼16%. Similarly, we synthesized CDs doped with different metals (M@CDs) including Ga, Sn, Zn, Ag, and Au. The interaction of M@CDs with neuron-like cells was examined and showed efficient uptake and low cytotoxicity. Moreover, the influence of the M@CDs on the improvement of neurites during initiation and elongation growth phases were compared with pristine CDs. Our research demonstrates the use of M@CDs for imaging and for neuronal interactions. The M@CD nanocomposites are promising due to their biocompatibility, photo-stability and potential selective affinity, paving the way for multifunctional biomedical applications.

Formation of metallic silver and copper in non-aqueous media by ultrasonic radiation.

Concentrated suspensions of silver and copper salts in silicone oil were heated to 200 °C and irradiated with ultrasonic energy for different time durations. Characterization of the products was done using X-ray powder diffraction. In most cases, metallic Ag or Cu were obtained, together with their oxide forms Ag2O and Cu2O. The salts, used as precursors, do not dissolve in silicone oil but rather form a heterogeneous system, and we assume that local heating, caused by the acoustic cavitation, enhanced their thermal decomposition and the formation of metallic particles. It was found that the presence of silver particles enhances the formation of metallic copper. This phenomenon was observed in the experiment with the acetate salts mixture.

Kinetics, Isotherm, and Thermodynamic Studies of Methylene Blue Adsorption on Polyaniline and Polypyrrole Macro-Nanoparticles Synthesized by C-Dot-Initiated Polymerization.

This work unraveled kinetics, isotherm, and thermodynamic properties of methylene blue (MB) adsorbed on polyaniline (PANI) and polypyrrole (PPY). The two polymers, PANI and PPY, synthesized by a facile C-dot (CD)-initiated polymerization method have been proven as the effective adsorbent materials to remove MB from wastewater. This dye model is also generally employed as a redox indicator in analytical chemistry and exhibits blue in an oxidizing environment, but it is colorless when exposed to a reducing agent. The effects of temperature, adsorbent amount contact time, and dye concentration were consistently examined. The adsorption capacity of the polymers at 28 °C could reach 19.2 mg/g. The adsorption equilibrium of the dye was attained after 90 and 120 min of contact time with PANI and PPY, respectively. The equilibrium details were well described by Freundlich and Langmuir isotherms. Results showed that PANI and PPY prepared using CD-initiated polymerization are better adsorbents compared to the commercial PANI powder for the removal of MB from water.

A hydrothermal reaction of an aqueous solution of BSA yields highly fluorescent N doped C-dots used for imaging of live mammalian cells.

In the current study, we present a new and facile synthesis of N doped C-dots (N@C-dots) by hydrothermally reacting an aqueous solution of Bovine Serum Albumin (BSA). The as-prepared quantum dots (QDs) exhibited high quantum yield (44%), high photostability, colloidal stability, and high functionalization efficiency. In addition to their low cost, the N@C-dots have demonstrated a non-toxic and long-lasting effect when applied for imaging human cells (human osteosarcoma U2OS cells). Importantly, with high physiological stability, excellent biocompatibility, and homogenous distribution, the N@C-dot suspension was exploited for high quality cell imaging and to model the biological effects at the nuclear level. Moreover, the water-soluble N@C-dots are nontoxic to the selected cell line in our preliminary evaluation.

Facile synthesis of self-assembled spherical and mesoporous dandelion capsules of ZnO: efficient carrier for DNA and anti-cancer drugs.

This work presents a new facile strategy to fabricate self-assembled spherical and mesoporous submicron-sized capsules, 'dandelions', of ZnO nanorods and nanoparticles. Self-assembled 'dandelion' capsules have been synthesized from Zn(Ac)2 and Igepal CO-520, and the mechanistic approach for the growth of self-assembled ZnO capsules has been elucidated. Physical characteristics of the novel capsules responsible for biomedical applications have been studied through XRD, Raman spectroscopy, UV-Vis-NIR spectroscopy, XPS and EPR. The mechanical stability of the capsules has been characterized using high energy ultrasound with time in 10% PBS buffer. The biocompatibility of the capsules has been investigated with a cell-based study using normal lymphocyte and K562 cancer cells through MTT assay. The loading and release efficiency of the fluorescent molecules (Rhodamine 6G), anti-cancer drugs (doxorubicin hydrochloride, DOX), and deoxyribonucleic acid (DNA) have been investigated. All the results indicate the high potential of self-assembled ZnO 'dandelion' capsules in relevant applications, such as for sustained drug delivery with the formation of a {(ZnO)n δ+-(DOX)m} complex and gene delivery with the formation of a {(ZnO)n δ+-(DNA)m complex, in medical biotechnology. The fabrication of such self-assembled idiosyncratic capsules is very simple, feasible, and cost effective; moreover, it demonstrates improved performance in drug and gene delivery applications.