Anticancer Platform Research Articles

Peptide-coated DNA nanostructures as a platform for control of lysosomal function in cells

DNA nanotechnology is a rapidly growing field that provides exciting tools for biomedical applications. Targeting lysosomal functions with nanomaterials, such as DNA nanostructures (DNs), represents a rational and systematic way to control cell functionality. Here we present a versatile DNA nanostructure-based platform that can modulate a number of cellular functions depending on the concentration and surface decoration of the nanostructure. Utilizing different peptides for surface functionalization of DNs, we were able to rationally modulate lysosomal activity, which in turn translated into the control of cellular function, ranging from changes in cell morphology to modulation of immune signaling and cell death. Low concentrations of decalysine peptide-coated DNs induced lysosomal acidification, altering the metabolic activity of susceptible cells. In contrast, DNs coated with an aurein-bearing peptide promoted lysosomal alkalization, triggering STING activation. High concentrations of decalysine peptide-coated DNs caused lysosomal swelling, loss of cell–cell contacts, and morphological changes without inducing cell death. Conversely, high concentrations of aurein-coated DNs led to lysosomal rupture and mitochondrial damage, resulting in significant cytotoxicity. Our study holds promise for the rational design of a new generation of versatile DNA-based nanoplatforms that can be used in various biomedical applications, like the development of combinatorial anti-cancer platforms, efficient systems for endolysosomal escape, and nanoplatforms modulating lysosomal pH.

ROS-Responsive and Self-Tumor Curing Methionine Polymer Library Based Nanoparticles with Self-Accelerated Drug Release and Hydrophobicity/Hydrophilicity Switching Capability for Enhanced Cancer Therapy.

The applications of amino acid-based polymers are impeded by their limited structure and functions. Herein, a small library of methionine-based polymers (Met-P) with programmed structure and reactive oxygen species (ROS)-responsive properties is developed for tumor therapy. The Met-P can self-assemble into sub-100nm nanoparticles (NPs) and effectively load anticancer drugs (such as paclitaxel (PTX) (P@Met-P NPs)) via the nanoprecipitation method. The screened NPs with superior stability and high drug loading are further evaluated in vitro and in vivo. When encountering with ROS, the Met-P polymers will be oxidized and then switch from a hydrophobic to a hydrophilic state, triggering the rapid and self-accelerated release of PTX. The in vivo results indicated that the screened P@2Met10 NPs possessed significant anticancer performance and effectively alleviated the side effects of PTX. More interestingly, the blank 2Met10 NPs displayed an obvious self-tumor inhibiting efficacy. Furthermore, the other Met-P NPs (such as 2Met8, 4Met8, and 4Met10) are also found to exhibit varied self-anti-cancer capabilities. Overall, this ROS-responsive Met-P library is a rare anticancer platform with hydrophobic/hydrophilic switching, controlled drug release, and self-anticancer therapy capability.

Emergence of in vitro antimicrobial photodynamic activities of perylene-dopamine and enhancement of its phototoxicity properties via chelating with FeIII and encapsulating in CMC-based safe hydrogel film

In the present work, we achieved a multifunctional antioxidant, antimicrobial, and anti-cancer platform by designing and encapsulating phenolic PDT drug/FeIII complex (PBI-DOPA/FeIII) into the CMC-based biocompatible hydrogel film matrix. The photosensitive CMC-CA/PBI-DOPA/FeIII system was synthesized via a one-pot process, in which the PBI-DOPA/FeIII complex can be trapped during the CMC cross-linking process by citric acid. The phenolic groups of PBI-DOPA can play a dual role, either being chelated by iron ions or otherwise imparting antioxidant properties to the hydrogel film. The presence of metal ions exerts an advantageous effect on oxygen production and phototoxicity of the photosensitive system by facilitating ISC (intersystem crossing). In vitro PDT potential of CMC-CA/PBI-DOPA/Fe (III) film and free PBI-DOPA was assessed on cancerous MCF-7 and non-cancerous MCF10A cell lines. As we expected, the PDT efficiency of encapsulated PBI-DOPA was dramatically enhanced compared to the free form and could induce up to 65% cancer cell apoptosis. Moreover, the photosensitive system proved effective antimicrobial activity against S.aureus (ATCC 6538) that greatly killed and inhibited the growth of microbes. Therefore, the innovative multifunctional CMC-CA/PBI-DOPA/Fe (III) hydrogel film with superior antioxidant, antimicrobial, and anticancer properties, which achieved enhanced cytotoxicity through PBI-DOPA/FeIII complexes, could serve as a promising efficient weapon in PDT against breast cancer and bacterial infections by minimizing side effects.

Preclinical Assessment of Enhanced Chemodynamic Therapy by an FeMnOx-Based Nanocarrier: Tumor-Microenvironment-Mediated Fenton Reaction and ROS-Induced Chemotherapeutic for Boosted Antitumor Activity.

In recent studies, iron-containing Fenton nanocatalysts have demonstrated significant promise for clinical use due to their effective antitumor activity and low cytotoxicity. A new approach was reported in this work utilizing cation exchange synthesis to fabricate FeMnOx nanoparticles (NPs) that boost Fenton reactions and responses to the tumor microenvironment (TME) for chemodynamic therapy (CDT) and chemotherapy (CT). Within the TME, the redox metal pair of Fe2+/Mn2+ helps break down endogenous hydrogen peroxide (H2O2) into very harmful hydroxyl radicals (•OH) while simultaneously deactivating glutathione (GSH) to boost CDT performance. To further enhance the therapeutic potential, FeMnOx NPs were encapsulated with thioketal-linked camptothecin (CPT-TK-COOH), a reactive oxygen species (ROS)-responsive prodrug, achieving a high CPT-loading capacity of up to 51.1%. Upon ROS generation through the Fenton reaction, the prodrug TK linkage was disrupted, releasing 80% of the CPT payload within 48 h. Notably, FeMnOx@CPT exhibited excellent dual-modal imaging capabilities, enabling magnetic resonance and fluorescence imaging for image-guided therapy. In vitro studies showed the cytocompatibility of FeMnOx NPs using MDA-Mb-231 and 4T1 cells, but in the presence of H2O2, they induced significant cytotoxicity, resulting in 80% cell death through CDT and CT effects. Upon intravenous administration, FeMnOx@CPT displayed remarkable tumor accumulation, which enhanced tumor suppression in xenografts through improved CDT and CT effects. Moreover, no significant adverse effects were observed in the FeMnOx NP-treated animals. In the current study, the FeMnOx@CPT anticancer platform, with its boosted •OH-producing capability and ROS-cleavable drug release, has been validated utilizing in vitro and animal studies, suggesting its capacity as a viable strategy for clinical trials.

Synthesis and characterization of bio-nanocomposite hydrogel beads based on magnetic hydroxyapatite and chitosan: a pH-sensitive drug delivery system for potential implantable anticancer platform

Synthesis and characterization of bio-nanocomposite hydrogel beads based on magnetic hydroxyapatite and chitosan: a pH-sensitive drug delivery system for potential implantable anticancer platform

Core-shell iron oxide-platinium@metal organic framework/epirubicin nanospheres: Synthesis, characterization and anti-breast cancer activity

Potential cancer therapy can be accomplished by utilizing nano-based platforms that supply facilitated drug penetration inside cancer cells. In this paper, an intelligent therapeutic nano-based system derived from metal–organic framework (MOF) core–shell hybrids with the capacity of potential drug loading, tumor microenvironment-triggered drug release as well as promising cell penetration was developed. The core–shell iron oxide-platinium@MOF/epirubicin (Fe3O4-Pt@MOF/EPI) nanospheres were constructed, where these nanoplatforms endow the system with the capability of pH-responsive drug release. The synthesized Fe3O4-Pt@MOF/EPI nanoparticles were characterized using different well-known techniques. The Fe3O4-Pt@MOF/EPI nanospheres were shown to have a dried size of around 50 nm (evidenced by SEM analysis), a spherical/core–shell/porous structure (evidenced by TEM), and an average hydrodynamic size of 92.89 nm (evidenced by DLS). Additionally, TGA analysis revealed that Fe3O4-Pt@MOF/EPI nanospheres had a weight loss at temperatures between 220 and 450 °C associated with the removal of MOF and EPI from the structure of core–shell nanospheres. The N2 adsorption–desorption data also reflected the porosity of core–shell Fe3O4-Pt@MOF nanospheres by indicating type IV behavior with an apparent hysteresis loop in the range of 0.38–0.98. Furthermore, XRD analysis disclosed the changes in the peak intensity at positions of 57.2° and 39.5°, which indicated the effects of loaded MOF on Fe3O4-Pt nanosphere. Moreover, core–shell Fe3O4-Pt@MOF/EPI nanospheres showed high loading capacity and drug release in a pH-responsive manner. Cell viability and cellular uptake assays on mouse fibroblast (NIH3T3) and triple-negative 4 T1 breast (TNFB) tumors showed that the core–shell Fe3O4-Pt@MOF/EPI nanospheres effectively inhibited TNFB cancer cells proliferation through inducing higher cell penetration compared to free EPI while having good biocompatibility against NIH3T3 cells. In conclusion, the present study may provide useful information about the development of efficient anticancer platforms against breast cancer cells, while further in vivo and pre-clinical assays are required to support this study.

Exploring the interaction of calycosin with cyclin D1 protein as a regulator of cell cycle progression in lung cancer cells

Cyclin D1 has been shown to play a pivotal role in the proliferation of lung cancer cells through regulation of cell cycle progression. Therefore, targeting this protein can be used as a potential strategy in lung cancer treatment. Calycosin has been reported to show potential anticancer effects, however, its possible anticancer mechanisms remain unclear. Therefore, in this study we aimed to explore the interaction of cyclin D1 and calycosin to determine the binding properties and probable structural changes of cyclin D1. We carried out in-depth experimental and computational binding assays of calycosin with cyclin D1 under simulated physiological environment, using intrinsic, extrinsic, synchronous fluorescence, circular dichroism, and differential scanning calorimetry (DSC) analysis. The results showed a spontaneous static mechanism driven from hydrogen bonding and van der Waals forces between hydrophilic residues of cyclin D1 with hydroxyl groups of calycosin. We determined that calycosin led to secondary and tertiary structural changes of cyclin D1 through exposure of hydrophobic residues. Also, it was determined that calycosin resulted in an apparent decrease in the heat capacity changes (ΔCp) and midpoint of unfolding transition (Tm) values of cyclin D1. Cellular studies also indicated that calycosin caused the inhibition of lung cancer cell proliferation through cell cycle arrest at G1 phase, which may be due to denaturation of cyclin D1, although it needs further investigation in the future studies. In general, this study may provide useful preliminary data about the development of calycosin-based anticancer platforms.

Surface engineered iron oxide nanozyme for synergistic chemodynamic/photodynamic therapy with glutathione depletion and hypoxia relief

Reactive oxygen species (ROS)-based therapies, such as photodynamic therapy (PDT) and chemodynamic therapy (CDT), hold great promise to cancer treatment. However, their efficacies are subject to hypoxia and overexpressed glutathione (GSH) in tumor microenvironment (TME). Herein, we develop Mn (II) ions and pyropheophorbide (PPa) engineered iron oxide nanoparticles (IMOP) to regulate tumor hypoxia and deplete GSH for synergistic CDT/PDT. In the TME, IMOP could catalytically decompose hydrogen peroxide (H2O2) to hydroxyl radicals (·OH) as a CDT agent. Significantly, IMOP exhibits high catalase-like and glutathione peroxidase-like activities simultaneously. Once enriching into tumor, IMOP could catalyze H2O2 to oxygen (O2) to overcome hypoxic TME for improved 1O2 generation via PPa-mediated PDT. Meanwhile, the glutathione peroxidase-like activity ensure IMO to reduce the intratumoral GSH concentration and further reduce the consumption of active ROS during therapy. We demonstrated that the regulation by IMOP elicited synergistic CDT/PDT efficacy for enhanced ROS-based cancer treatment both in vitro and in vivo. Moreover, the existence of Mn (II) allowed IMO with T1 contrast behavior to monitor the progress of CDT/PDT in magnetic resonance imaging. This work provides a new guidance for designing TME-based anticancer platform for effective and precise cancer treatment.

Ultrathin tellurium nanosheets for simultaneous cancer thermo-chemotherapy

The emerging two-dimensional monoelemental materials (2D Xenes) have been commonly supposed as promising drug delivery carriers, photothermal and photodynamic therapeutic agents, biosensors, theranostics, and some other candidates for biomedical applications. Here, high-performance and bioactive ultrathin 2D Tellurium nanosheets (Te NSs) are prepared by a simple but efficient liquid-phase exfoliation approach. The as-obtained Te NSs possess a mean size of ∼90 nm and a mean thickness of ∼5.43 nm. The pegylation Te NSs (Te-PEG NSs) possess excellent biocompatibility and stability. The Te-PEG NSs could generate local hyperthermia with a remarkable photothermal conversion efficiency of about 55% under 808 nm laser irradiation. Additionally, Te-PEG NSs exhibit an extremely high loading capacity of chemo drug (∼162%) owing to their ultra-high surface area and tumor microenvironment-triggered drug release superiority. The results of in vivo experiments show that the Te-PEG NSs have higher tumor elimination efficiency via the combination of photothermal and chemotherapy, comparing to any other single therapeutic modalities. Therefore, our work not only highlights the promising potentials of tellurene as an ideal anti-cancer platform but also expands the application of 2D Te for cancer nanomedicine.

Human small intestine cancer cell membrane-camouflaged quercetin-melanin for antibacterial and antitumor activity.

E. coli has become an important factor that can lead to cancer because of its ability to cause diverse intestinal changes. Nano-polymer materials provide ideal drug delivery systems for preparing antibacterial and anti-cancer drugs because of their unique structure, easy modification, and high drug loading. The modified natural melanin has the potential to be an excellent nano-carrier. By improving the water-solubility and biocompatibility of the loaded natural drug quercetin, the antibacterial effect of quercetin can be fully played. Here, natural melanin was extracted from frozen squid to synthesize carrier polydopamine (PDA) nanoparticles, and the natural drug quercetin (Q) was modified on the surface of PDA by π-π bond and covalent bond action to produce melanin-quercetin (PDA-Q). We also developed human small intestinal cancer cells (HIC) membrane-camouflaged melanin-Quercetin (PDA-Q) nanoparticles as an anti-cancer platform in vivo. The potential bacteriostatic mechanism was likely driven by the penetration of PDA-Q in E. coli cells, damaging the integrity of the membranes of E. coli and inducing cell death. The mice wound experiment and bacteremia model experiment revealed that C@PDA-Q had a strong inhibitory effect on E. coli in vivo. In addition, the results of the in vitro tumor test also revealed that C@PDA-Q had strong anti-tumor activity against HIC cells of human small intestinal cancer, and the IC50 value was 12.3 ± 0.7 μg/ml, which was slightly better than that for cisplatin. As both melanin nanoparticles and HIC membrane are natural biomaterials, the synthesized C@PDA-Q nano-polymer material shows great potential for use in anti-cancer nano-drug loading.

Thermodynamic and anticancer properties of inorganic zinc oxide nanoparticles synthesized through co-precipitation method

In this paper, inorganic zinc oxide nanoparticles (ZnO NPs) were synthesized through co-precipitation method and after evaluating their physicochemical properties by using TEM and XRD techniques, the bio-thermodynamic and structural parameters upon interaction of ZnO NPs with human serum albumin (HSA) were determined by using fluorescence, UV–vis, CD and molecular docking studies. Also, the selective anticancer effects of ZnO NPs on leukemia (K562) cells were explored by using different cellular and molecular assays. It was determined that the crystalline structure of ZnO NPs has a diameter of about 30 nm. Thermodynamic parameters and docking analysis indicated that the hydrophobic forces mediate the formation of static complex between ZnO NPs and HSA molecules. UV–vis and CD spectroscopic methods showed that the melting temperature (Tm) and secondary structure of HSA, respectively remain substantially unchanged by increase of ZnO NPs. Anticancer assays demonstrated that ZnO NPs trigger an inhibitory impact on the proliferation of K562 cells while being safe against lymphocyte normal cells. Exposure of K562 cells to ZnO NPs resulted in membrane leakage, activation of caspase-9, -3, overexpression of Bax/Bcl-2 mRNA ratio, increase in the level of ROS, cell cycle arrest, and apoptosis/necrosis. In conclusion, it may be suggested that ZnO NPs can be utilized as potential agents in the development of anticancer platforms.

Ruthenium Complexes as Anticancer Agents: A Brief History and Perspectives.

Platinum (Pt)-based anticancer drugs such as cisplatin have been used to treat various cancers. However, they have some limitations including poor selectivity and toxicity towards normal cells and increasing chemoresistance. Therefore, there is a need for novel metallo-anticancers, which has not been met for decades. Since the initial introduction of ruthenium (Ru) polypyridyl complex, a number of attempts at structural evolution have been conducted to improve efficacy. Among them, half-sandwich Ru-arene complexes have been the most prominent as an anticancer platform. Such complexes have clearly shown superior anticancer profiles such as increased selectivity toward cancer cells and ameliorating toxicity against normal cells compared to existing Pt-based anticancers. Currently, several Ru complexes are under human clinical trials. For improvement in selectivity and toxicity associated with chemotherapy, Ru complexes as photodynamic therapy (PDT), and photoactivated chemotherapy (PACT), which can selectively activate prodrug moieties in a specific region, have also been investigated. With all these studies on these interesting entities, new metallo-anticancer drugs to at least partially replace existing Pt-based anticancers are anticipated. This review covers a brief description of Ru-based anticancer complexes and perspectives.

Dual stimuli-responsive ursolic acid-embedded nanophytoliposome for targeted antitumor therapy.

The hindrances in achieving clinically translatable anticancer platforms are being tackled through nanotechnology-based formulations. In this study, stimuli-responsive, phytoactive constituent-loaded nanophytoliposomes were fabricated for designing a specific antitumor platform. Ursolic acid (UA)-loaded nanophytoliposomes (UA-PLL-HA.P) enwrapped in a poly-L-lysine (PLL) coat and hyaluronic acid (HA) were nanosized; these nanophytoliposomes had spherical morphology, slightly negative charge, and an in-range polydispersity index (~0.25). Successful fabrication of the nanosystem was proven through several characterization methods and the pH- and enzyme-responsiveness of the nanosystem was assessed through a release study. The cellular internalization in CD44 receptor-expressing cell lines was amplified by enhanced permeation and retention as well as by active targeting. In vitro antitumor behavior was confirmed through in vitro cytotoxic and apoptotic activity of the nanosystem. Similarly, in vivo imaging showed exceptional biodistribution in the tumor in agreement with the in vitro findings. Moreover, the tumor inhibitory rate of UA-PLL-HA.P was significantly higher, and was ascribed to the targeting potential and stimuli-responsiveness. In summary, UA-PLL-HA.P exhibited pronounced anticancer effect and could open a number of possibilities for discovering novel phytoconstituent-incorporated nanoformulations.

PVP-stabilized tungsten oxide nanoparticles: pH sensitive anti-cancer platform with high cytotoxicity.

Photochromic tungsten oxide (WO3) nanoparticles stabilized by polyvinylpyrrolidone (PVP) were synthesized to evaluate their potential for biomedical applications. PVP-stabilized tungsten oxide nanoparticles demonstrated a highly selective cytotoxic effect on normal and cancer cells in vitro. WO3 nanoparticles were found to induce substantial cell death in osteosarcoma cells (MNNG/HOS cell line) with a half-maximal inhibitory concentration (IC50) of 5mg/mL, while producing no, or only minor, toxicity in healthy human mesenchymal stem cells (hMSc). WO3 nanoparticles induced intracellular oxidative stress, which led to apoptosis type cell death. The selective anti-cancer effects of WO3 nanoparticles are due to the pH sensitivity of tungsten oxide and its capability of reactive oxygen species (ROS) generation, which is expressed in the modulation of genes involved in reactive oxygen species metabolism, mitochondrial dysfunction, and apoptosis.

Core/Shell Structured Fe₃O₄@TiO₂-DNM Nanospheres as Multifunctional Anticancer Platform: Chemotherapy and Photodynamic Therapy Research.

The dose-dependent toxicity and low specificity against cancerous cells have restricted the clinical use of daunomycin (DNM). Titanium dioxide (TiO2) has been wildly used as an inorganic photodynamic therapy (PDT) agent and drug carrier. To facilitate the targeted drug delivery and combined therapy, in the present study, TiO2-coated Fe3O4 nanoparticles (Fe3O4@TiO2 NPs) were employed to load DNM and the drug-loaded Fe3O4@TiO2-DNM Nps exhibited smart pH-controlled releasing and satisfactory cytotoxicity as well as photocytotocity. The combination of prussian blue staining and fluorescence methods evidenced the effortless cell internalization of the fabricated Fe3O4@TiO2-DNM Nps for the cancer cells. The cell cycle status experiments indicated that the as-prepared nanospheres arrested the S and G2/M periods of the cancer cell proliferation in the dark, and further induced the apoptosis under the irradiation of ultraviolet light. The cell apoptotic results revealed that the apoptosis induced by the Fe3O4@TiO2-DNM Nps was in the early stage. The constructed Fe3O4@TiO2-DNM NPs have been endowed with multifunctions that allow them to selectively deliver combinatorial therapeutic payload and exhibit integrated therapeutic effectiveness to tumors.

Ag-carried CMC/functional copolymer/ODA-Mt wLED-treated NC and their responses to brain cancer cells

The subject of this work is synthesis and characterization of novel multifunctional nanocomposite (8/2A-NC) consisting (1) carboxymethyl cellulose (CMC) as a matrix biopolymer and poly (maleic acid-alt-acrylic acid) as a reactive synthetic partner matrix polymer; (2) octadecyl amine montmorillonite (ODA-MMT) reactive organoclay provide intercalated silicate layers structures and aqueous colloidal dispersing medium, and MMT as carriers and targeting agents for anticancer agents in drug delivery systems, respectively. ODA as a intercalated surfactant finely dispersed 8/2A NC and its compatibility with matrix polymers via the interfacial polarization (complexing) and functionalization of matrix polymers by amine (ODA) and carboxylic acids from both the CMC and copolymer; (3) silver nanoparticles (AgNPs) as in-situ generated onto matrix polymers with unique nano-size and morphology parameters was synthesized. Important material science and bioengineering aspects of these investigations included (a) novel approach in synthetic pathways; (b) effects of physical and chemical structural rearrangements; (c) effects of Light Emitting Dioda (LED)-treatment on the FT-IR spectra, XRD reflection parameters, SEM-TEM morphology and nano-size and diameter distribution of AgNPs onto matrix polymers; (d) positive effect of LED-treatment of 8/2A nanocomposite and its response to the MIAPaCa-2 and U87 human brain cancer cell lines were evaluated. Novel 8/2A-NC multifunctional drug consisting unique positive, intercalating and encapsulated core-shell morphology structures, nano-size (5.6 nm) and narrow diameter distribution (94%) of AgNPs onto matrix polymers [silver NPs (0.25%) in 8/2A NC (25%)] with highest volume of contact area compared with used cancer micro-cells show lowest cell viability as an excellent anticancer platform. 8/2A-NC is a novel multifunctional drug with intercalating and encapsulated core-shell morphology structures consisting of positively charged, non-randomly distributed AgNPs with a large contact area and low diameters (5–6 nm). The anticancer properties of (This factor is not conformed experimentally in work) this drug can be explained by the following structural factors: 8/2A-NC contains a combination of active sites from protonated hydroxyl, carboxyl and amine groups; Ag+-cations and ODA-MMT with high physical and chemical surface areas. We suggest this material be further explored for anti-cancer testing.

Oncolytic Viruses: The Best is Yet to Come.

Oncolytic viruses are a promising anti-cancer platform, achieving significant pre-clinical and clinical milestones in recent years. A full arsenal of selective, safe, and effective viruses has been developed with some emerging pre-clinical research focusing on optimizing these therapies in the face of remaining challenges, both in the bloodstream and in the tumour microenvironment. Herein we discuss the recent progress in pre-clinical virotherapy research to address these challenges, with special focus on innovative strategies that seek to complement the current strengths of virotherapy, ensuring an optimal multi-faceted attack on cancer. This review highlights the research areas that we believe provide the most potential to increase the efficacy of this exciting biotherapy platform: cell carriers, tumour vascular destruction, microenvironment modulation, combination therapies, and virus-mediated anti-tumour immune responses.

Novel colloidal poly(MA-alt-1-dodecene)-g-PEO/ODA-MMT/AgNPs nanohybrid composites as antimicrobial, antifungal and anticancer platforms

Novel colloidal poly(MA-alt-1-dodecene)-g-PEO/ODA-MMT/AgNPs nanohybrid composites as antimicrobial, antifungal and anticancer platforms

Surface modification and characterization of GO/polymer thin coatings as excellent bio-active platforms for tissue regeneration

Osteo-integration and tissue regeneration are vital for the longevity, durability, and unremitting functionality of medical implants/scaffolds implanted in vivo. It's essential for biomaterials used for in vivo implantation to induce the cellular secretion of growth factors, necessary for the desired tissue generation, since the administration of artificial growth factors, in vivo, is largely prohibited. Plasma functionalized (N2 and O2) and stabilized Graphene Oxide (GO) thin layers in a hybrid with amorphous carbon (aC) induced the expression of vascular endothelial growth factor (VEGF) and osteoprotegerin (OPG) growth factors in fibroblasts (hGF) and, more remarkably, in osteoblasts (hFOB) cells confirming the suitability for tissue regeneration and osteo-integration applications. We also observed a negative trend between hGF fibroblasts, but not hFOB osteoblasts, cellular viability and GO presence in the hybrid films that might indicate the phenomenon of oxidative stress. We traced that back to the presence of higher concentrations of carboxyl and the carbonyl groups on the surface of the GO rich coatings. The above described properties provided by GO coatings might be desirable for bio-selectivity applications and for the reduction of the undesired fibrosis process that is associated with medical implants in vivo environment. Moreover, novel plasma functionalized GO/polymer hybrid thin coating hybrid compositions are promising candidates for tissue engineering and bioengineering applications as excellent antimicrobial and anticancer platforms.

Magnetic metal-complex-conducting copolymer core\u2013shell nanoassemblies for a single-drug anticancer platform

Nanoparticulate agents for magnetic drug delivery systems (DDSs) have extensive applications in targeted drug delivery, contrast imaging and therapeutics. However, no simple synthetic method for magnetic DDS agents has been developed without the need to add magnetic nanoparticles. Here, we describe the one-step fabrication of ‘all-in-one’ magneto-assemblies using an ‘inorganic-metal-salt-free’ method, involving spontaneous self-assembly of the water-insoluble prodrug μ-oxo-bis(N,N′-ethylenebis(salicylideniminato)iron) [Fe(salen)] (magnetic core) with polypyrrole (PPy)-b-polycaprolactone (PCL) smart diblock copolymers. In the system, PCL serves as a heat-responsive core scaffold, and PPy serves as an electronic core-size controller and pH-responsive shell. This core–shell nanocomposite has a high-loading capacity (~90%), and the core size is tunable by incorporating albumin or gum arabic as bio-coating agents, which also provide colloidal stability, biocompatibility and thermo-stability. Fe(salen), which has intrinsic antitumor activity, also has ubiquitous magnetic properties, which are dramatically enhanced in these molecular assemblies with magnetic coupling. Moreover, these multifunctional nanoassemblies can be delivered magnetically, can serve as magnetic resonance imaging contrast agents, can generate magneto-hyperthermal effects and can enable magnetic field-triggered release of Fe(salen) molecules under acidic conditions.