Magnetic and pH-responsive magnetite/chitosan (core/shell) nanoparticles for dual-targeted methotrexate delivery in cancer therapy.

Methotrexate successful therapy encounters various challenges in chemotherapy, such as poor oral bioavailability, low specificity, side effects and the development of drug resistances. In this study, it is proposed a dual-targeted nanocarrier comprising magnetite/chitosan nanoparticles for an efficient Methotrexate delivery. The formation of the particles was confirmed through morphological analysis using electron microscopy and elemental mappings via energy dispersive X-ray spectroscopy. These nanoparticles exhibited a size of ≈ 270 nm, a zeta potential of ≈ 24 mV, and magnetic responsiveness, as demonstrated by hysteresis cycle analysis and visual observations under a magnetic field. In addition, these particles displayed high stability, as evidenced by size and surface electric charge measurements, during storage at both 4 ºC and 25 ºC for at least 30 days. Electrophoretic properties were examined in relation to pH and ionic strength, confirming these core/shell nanostructure. The nanoparticles demonstrated a pH-responsive drug release as observed by a sustained Methotrexate release over the next 90 h under pH ≈ 7.4, while complete release occurred within 3 h under acidic conditions (pH ≈ 5.5). In the biocompatibility assessment, the magnetite/chitosan particles showed excellent hemocompatibility ex vivo and no cytotoxic effects on normal MCF-10 A and cancer MCF-7 cells. Furthermore, the Methotrexate-loaded nanoparticles significantly enhanced the antitumor activity reducing the half-maximal inhibitory concentration by ≈ 2.7-fold less compared to the free chemotherapeutic.

Anti-quorum sensing activity of α-amidoamides against Agrobacterium tumefaciensNT1: Insights from molecular docking and dynamic investigations to synergistic approach of metronidazole release from gel formulations.

A unique approach is imperative for the development of drugs aimed at inhibiting various stages of infection, rather than solely focusing on bacterial viability. Among the array of unconventional targets explored for formulating novel antimicrobial medications, blocking the quorum-sensing (QS) system emerges as a highly effective and promising strategy against a variety of pathogenic microbes. In this investigation, we have successfully assessed nine α-aminoamides for their anti-QS activity using Agrobacterium tumefaciensNT1 as a biosensor strain. Among these compounds, three (2, 3and, 4) have been identified as potential anti-QS candidates. Molecular docking studies have further reinforced these findings, indicating that these compounds exhibit favorable pharmacokinetic profiles. Additionally, we have assessed the ligand's stability within the protein's binding pocket using molecular dynamics (MD) simulations and MMGBSA analysis. Further, combination of antiquorum sensing properties with antibiotics viaself-assembly represents a promising approach to enhance antibacterial efficacy, overcome resistance, and mitigate the virulence of bacterial pathogens. The release study also reflects a slow and gradual release of the metronidazole at both pH 6.5 and pH 7.4, avoiding the peaks and troughs associated with more immediate release formulations.

Dendritic polymer prodrug-based unimolecular micelles for pH-responsive co-delivery of doxorubicin and camptothecin with synergistic controlled drug release effect.

Combination chemotherapy has been recognized as a more powerful strategy for tumor treatment rather than the single chemotherapy. However, the interactive mechanism of the two hydrophobic chemotherapeutic drugs has not been explored by now. Aiming for a better synergistic effect, such interactive mechanism was investigated in the present work, by designing CPT@DOX-DPUTEA-PEG nanomedicine with encapsulated camptothecin (CPT) and conjugated doxorubicin (DOX). The synergistic controlled drug release effect was found for the two drugs loaded on the different sites of the dendritic polyurethane core. Synergism was achieved on the HepG2 cells with a combination index (CI) of 0.58 in the in vitro cellular experiments. The results demonstrated the promising application of the unimolecular micelles-based nanomedicine with independently loading of two hydrophobic chemotherapeutic drugs.

Preparation of pH-responsive polyurethane nano micelles and their antibacterial application.

Considering the differences in pH between bacterial infection microenvironment and normal tissues, a series of pH-responsive drug-release amphiphilic polyurethane copolymers (DPU-g-PEG) have been prepared in this work. Fourier transform infrared (FT-IR) spectroscopy and 1H NMR was selected to detect the structure of the condensed polymers. The DPU-g-PEG amphiphilic copolymers could form stable micelles with a hydrophilic shell of polyethylene glycol (PEG) and a hydrophobic core of polylactic acid (PLA). We loaded a model drug called triclosan onto DPU-g-PEG micelles and studied how pH affects their particle size, Zeta potential, and drug release performance. The results revealed that when exposed to acidic conditions, the surface potential of DPU-g-PEG micelles changed, the micelles' particle size increased, and the drug release performance was significantly enhanced. These results suggested that the micelles prepared in this study can release more antibacterial substances at sites of bacterial infection. Meanwhile, we also investigated the impact of different ratios of soft and hard segments on the properties of micelles, and the results showed that the pH responsiveness of micelles was strongest when the ratio of soft segments (PLLA diol + PEG 2000): 1,6-hexamethylene diisocyanate (HDI): 2,6-Bis-(2-hydroxy-ethyl)-pyrrolo[3,4-f]isoindole-1,3,5,7-tetraone (DMA) = 1: 1.2: 0.2. Furthermore, the results of inhibition zone test, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) all confirmed the antibacterial activity of triclosan-load DPU-g-PEG micelles. In conclusion, the DPU-g-PEG micelles produced in this study have the potential to be used as intelligent drug delivery systems in the biomedical field.

Carfilzomib-Loaded Ternary Polypeptide Nanoparticles Stabilized by Polycationic Complexation.

Carfilzomib (CFZ) is a second-generation proteasome inhibitor showing great efficacy in multiple myeloma treatment, yet its clinical applications for other diseases such as solid cancers are limited due to low aqueous solubility and poor biostability. Ternary polypeptide nanoparticles (tPNPs) are drug carriers that we previously reported to overcome these pharmaceutical limitations by entrapping CFZ in the core of the nanoparticles and protecting the drugs from degradation in biological media. However, preclinical studies revealed that tPNPs would require further improvement in particle stability to suppress initial burst drug release and thus achieve prolonged inhibition of proteasome activity with CFZ against tumor cells in vivo. In this study, CFZ-loaded tPNPs are stabilized by polycations which have varying pKa values and thus differently modulate nanoparticle stability in response to solution pH. Through polyion complexation, the polycations appeared to stabilize the core of tPNPs entrapping CFZ-cyclodextrin inclusion complexes while allowing for uniform particle size before and after freeze drying. Interestingly, CFZ-loaded tPNPs (CFZ/tPNPs) showed pH-dependent drug release kinetics, which accelerated CFZ release as solution acidity increased (pH < 6) without compromising particle stability at the physiological condition (pH 7.4). In vitro cytotoxicity and proteasome activity assays confirmed that tPNPs stabilized with cationic polymers improved bioactivity of CFZ against CFZ-resistant cancer cells, which would be greatly beneficial in combination with pH-dependent drug release for treatment of solid cancers with drug resistance and tumor microenvironment acidosis by using CFZ and other proteasome inhibitors.

A mesoporous polydopamine-derived nanomedicine for targeted and synergistic treatment of inflammatory bowel disease by pH-Responsive drug release and ROS scavenging.

Repurposing clinically approved drugs to construct novel nanomedicines is currently a very attractive therapeutic approach. Selective enrichment of anti-inflammatory drugs and reactive oxygen species (ROS) scavenging at the region of inflammation by stimuli-responsive oral nanomedicine is an effective strategy for the treatment of inflammatory bowel disease (IBD). This study reports a novel nanomedicine, which is based on the excellent drug loading and free radical scavenging ability of mesoporous polydopamine nanoparticles (MPDA NPs). By initiating polyacrylic acid（PAA）polymerization on its surface, a "core-shell" structure nano-carrier with pH response is constructed. Then, under alkaline conditions, using the π-π stacking and hydrophobic interaction between the anti-inflammatory drug sulfasalazine (SAP) and MPDA, the nanomedicines (PAA@MPDA-SAP NPs) loaded efficiently (928 µ g mg-1) of SAP was successfully formed. Our results reveal that PAA@MPDA-SAP NPs can pass through the upper digestive tract smoothly and finally accumulate in the inflamed colon. Through the synergistic effect of anti-inflammation and antioxidation, it can effectively reduce the expression of pro-inflammatory factors and enhance the intestinal mucosal barrier, and finally significantly alleviate the symptoms of colitis in mice. Furthermore, we confirmed that PAA@MPDA-SAP NPs have good biocompatibility and anti-inflammatory repair ability under inflammation induction through human colonic organoids. In summary, this work provides a theoretical basis for the development of nanomedicines for IBD therapy.

A pH-Responsive Asymmetric Microfluidic/Chitosan Device for Drug Release in Infective Bone Defect Treatment.

Bacterial infection is currently considered to be one of the major reasons that leads to the failure of guided bone regeneration (GBR) therapy. Under the normal condition, the pH is neutral, while the microenvironment will become acid at the sites of infection. Here, we present an asymmetric microfluidic/chitosan device that can achieve pH-responsive drug release to treat bacterial infection and promote osteoblast proliferation at the same time. On-demand release of minocycline relies on a pH-sensitive hydrogel actuator, which swells significantly when exposed to the acid pH of an infected region. The PDMAEMA hydrogel had pronounced pH-sensitive properties, and a large volume transition occurred at pH 5 and 6. Over 12 h, the device enabled minocycline solution flowrates of 0.51-1.63 µg/h and 0.44-1.13 µg/h at pH 5 and 6, respectively. The asymmetric microfluidic/chitosan device exhibited excellent capabilities for inhibiting Staphylococcus aureus and Streptococcus mutans growth within 24 h. It had no negative effect on proliferation and morphology of L929 fibroblasts and MC3T3-E1 osteoblasts, which indicates good cytocompatibility. Therefore, such a pH-responsive drug release asymmetric microfluidic/chitosan device could be a promising therapeutic approach in the treatment of infective bone defects.

Enzymatic PCL-grafting to NH2-end grouped silica and development of microspheres for pH-stimulated release of a hydrophobic model drug.

This study set out to evaluate novel PCL-based silica containing nanohybrids as the polymer matrix in a hydrophobic drug-loaded microsphere system. Nanohybrids were synthesized by PCL-grafting to NH2-end grouped silica by in situ enzymatic ring opening polymerization of ε-caprolactone. Molecular weight and monomer conversion, PCL grafting percentage, thermal properties and crystallinity of the nanohybrids were determined by 1H NMR, TGA, DSC and XRD. Synthesized nanohybrids had low crystallinity percentage (32 and 39 %) and molecular weight (4800 and 8700 g/mol), promising for controlled drug release applications. The nanohybrids were used for fabrication of trans-chalcone-loaded microspheres by O/W single emulsion solvent evaporation. Mean particle diameter of the microspheres were between 15 and 30 µm. The result of release studies showed that optimum microsphere formulations (AP4 and A2, respectively) had 61 and 64 % encapsulation efficiency. One of the more significant findings to emerge from this investigation is that TC release was extended to 16 and 37 days, in a controlled manner. TC release was significantly enhanced in acidic pH media (pH 3.6 and 5.6) indicating pH-dependent release from nanohybrid microspheres; releasing 80-100 % of the loaded drug in 4-14 days. Drug/polymer interactions and molecular structures were investigated by FT-IR spectroscopy and DSC analysis. According to the results obtained, enzymatically synthesized nanohybrids have potential for pH-dependent release of the model drug, trans-chalcone.

Engineered Magnetic Polymer Nanoparticles Can Ameliorate Breast Cancer Treatment Inducing Pyroptosis-Starvation along with Chemotherapy.

Nanotechnology has shown a revolution in cancer treatments, including breast cancers. However, there remain some challenges and translational hurdles. Surgery, radiotherapy, and chemotherapy are the primary treatment methods for breast cancer, although drug combinations showed promising results in preclinical studies. Herein we report the development of a smart drug delivery system (DDS) to efficiently treat breast cancer by pyroptosis-starvation-chemotherapeutic combination. Cancer-starvation agent glucose oxidase was chemically attached to synthesized iron oxide nanoparticles which were entrapped inside poly(lactic-co-glycolic acid) along with apoptosis-associated speck-like protein containing a caspase recruitment domain plasmid and paclitaxel (PTX). An emulsion solvent evaporation method was used to prepare the DDS. The surface of the DDS was modified with chitosan to which aptamer was attached to achieve site-specific targeting. Hence, the prepared DDS could be targeted to a tumor site by both external magnet and aptamer to obtain an enhanced accumulation of drugs at the tumor site. The final size of the aptamer-decorated DDS was less than 200 nm, and the encapsulation efficiency of PTX was 76.5 ± 2.5%. Drug release from the developed DDS was much higher at pH 5.5 than at pH 7.4, ensuring the pH sensitivity of the DDS. Due to efficient dual targeting of the DDS, in vitro viability of 4T1 cells was reduced to 12.1 ± 1.6%, whereas the nontargeted group and free PTX group could reduce the viability of cells to 29.2 ± 2.4 and 46.2 ± 1.6%, respectively. Our DDS showed a synergistic effect in vitro and no severe side effects in vivo. This DDS has strong potential to treat various cancers.

pH-responsive graphene oxide loaded with targeted peptide and anticancer drug for OSCC therapy.

Oral squamous cell carcinoma (OSCC) is the most common type of cancer occurring in the oral and maxillofacial regions. Despite of the advances in the diagnosis and treatment, the overall 5-year survival rate has remained about 40%-50% in the past decades. Various nanotechnology-based carrier systems have been investigated for their potentials in the OSCC treatment. However, because of the lack of active targeting of tumors, their application is limited. Studies have shown that gastrin-releasing peptide receptors (GRPRs) are overexpressed on many human cancers, including head and neck squamous cell carcinoma. Herein, we aimed to develop a GRPR-targeted nano-graphene oxide (NGO) nanoprobe drug delivery system for OSCC therapy. DOX@NGO-BBN-AF750 was synthesized by the non-covalent bonding method to couple carboxylated NGO with BBN-AF750 (bombesin antagonist peptides conjugated to Alexa Fluor 750) and DOX (doxorubicin) through π-π and hydrogen bonding. Internalization and antitumor activities were carried out in human HSC-3 cancer cells. The tumor pH microenvironment was simulated to study the release of antitumor drug DOX from the DOX@NGO-ant BBN-AF750 complex under different pH conditions. DOX@NGO-BBN-AF750 showed internalization into HSC-3 cells. The IC50 (50% inhibitory concentration) was 5 µg/ml for DOX@NGO-BBN-AF750 in HSC-3 cells. Furthermore, DOX@NGO-BBN-AF750 showed a pH-sensitive drug release rate, and a dose-dependent and pH-responsive cytotoxicity in HSC-3 cells. DOX@NGO-BBN-AF750 presents the characteristics ensuring a slow release of DOX from the nanoprobe, thereby protecting the drug from degradation and prolonging the half-life of the drug. This report provides a versatile strategy to achieving targeted and imaging-guided therapy of OSCC.

Gold Nanoparticle Embedded Stimuli-Responsive Functional Glycopolymer: A Potential Material for Synergistic Chemo-Photodynamic Therapy of Cancer Cells.

Photodynamic therapy has emerged as a noninvasive treatment modality for several types of cancers. However, conventional hydrophobic photosensitizers (PS) suffer from low water solubility and poor tumor-targeting ability. Therefore, PS modified with glycopolymers can offer adequate water solubility, biocompatibility, and tumor-targeting ability due to the presence of multiple sugar units. In this study, a well-defined block copolymer poly(3-O-methacryloyl-d-glucopyranose)-b-poly(2-(4-formylbenzoyloxy)ethylmethacrylate) (PMAG-b-PFBEMA) containing pendant glucose and aldehyde units is synthesized via reversible addition-fragmentation chain transfer polymerization method. A water-soluble PS (toluidine blue O; TBO) and a potent anticancer drug, Doxorubicin (Dox) are introduced to the polymer backbone via acid-labile Schiff-base reaction (PMAG-b-PFBEMA_TBO_Dox). The PMAG-b-PFBEMA_TBO_Dox is then anchored on the surface of gold nanoparticles (AuNPs) via electrostatic interaction. This hybrid system exhibits excellent reactive oxygen species (ROS) generating ability under exposure of 630 nm light-emitting diode along with triggered release of Dox under the acidic pH of tumor cells. The in vitro cytotoxicity study on human breast cancer cell line, MDA MB 231, for this hybrid system shows promising results due to the synergistic effect of ROS and Dox released. Thus, this glycopolymer-based dual (chemo-photodynamic) therapy model can work as potential material for future therapeutics.

Injectable, self-healable and adhesive hydrogels using oxidized Succinoglycan/chitosan for pH-responsive drug delivery.

We prepared chitosan (CS) based multifunctional hydrogels using oxidized succinoglycan (OSG) with a semi-dissolving acidified sol-gel transition method. OSG cross-linked CS hydrogels (OSG/CS) was prepared by aldehyde-amine Schiff-base reaction. OSG/CS increased not only thermal stability but also improved mechanical strength by 5.75 times. Through the tensile and strain sweep test, OSG/CS showed excellent self-healing properties by 98.82% and 99.89%, respectively. It showed the high compressive stress of 173 kPa at 60% strain, the adhesive strength of 2763 kPa, and the antibacterial effect of 90%. Furthermore, OSG/CS showed a pH-controlled drug release pattern, where a change of pH from 7.4 to 2.0 accelerated for 5-fluorouracil release from 60% to 90%. WST-8 assay demonstrated that OSG/CS maintained 97.30% cell viability and 98.84% cell proliferation after 7 days, indicating the potential as biocompatible hydrogel materials such as wound healing, tissue engineering and drug release systems.

A Tri-Stimuli Responsive (Maghemite/PLGA)/Chitosan Nanostructure with Promising Applications in Lung Cancer.

A (core/shell)/shell nanostructure (production performance ≈ 50%, mean diameter ≈ 330 nm) was built using maghemite, PLGA, and chitosan. An extensive characterization proved the complete inclusion of the maghemite nuclei into the PLGA matrix (by nanoprecipitation solvent evaporation) and the disposition of the chitosan shell onto the nanocomposite (by coacervation). Short-term stability and the adequate magnetism of the nanocomposites were demonstrated by size and electrokinetic determinations, and by defining the first magnetization curve and the responsiveness of the colloid to a permanent magnet, respectively. Safety of the nanoparticles was postulated when considering the results from blood compatibility studies, and toxicity assays against human colonic CCD-18 fibroblasts and colon carcinoma T-84 cells. Cisplatin incorporation to the PLGA matrix generated appropriate loading values (≈15%), and a dual pH- and heat (hyperthermia)-responsive drug release behaviour (≈4.7-fold faster release at pH 5.0 and 45 °C compared to pH 7.4 and 37 °C). The half maximal inhibitory concentration of the cisplatin-loaded nanoparticles against human lung adenocarcinoma A-549 cells was ≈1.6-fold less than that of the free chemotherapeutic. Such a biocompatible and tri-stimuli responsive (maghemite/PLGA)/chitosan nanostructure may found a promising use for the effective treatment of lung cancer.

Enzymatic/Magnetic Hybrid Micromotors for Synergistic Anticancer Therapy.

Micro/nanomotors (MNMs), which propel by transforming various forms of energy into kinetic energy, have emerged as promising therapeutic nanosystems in biomedical applications. However, most MNMs used for anticancer treatment are only powered by one engine or provide a single therapeutic strategy. Although double-engined micromotors for synergistic anticancer therapy can achieve more flexible movement and efficient treatment efficacy, their design remains challenging. In this study, we used a facile preparation method to develop enzymatic/magnetic micromotors for synergetic cancer treatment via chemotherapy and starvation therapy (ST), and the size of micromotors can be easily regulated during the synthetic process. The enzymatic reaction of glucose oxidase, which served as the chemical engine, led to self-propulsion using glucose as a fuel and ST via a reduction in the energy available to cancer cells. Moreover, the incorporation of Fe3O4 nanoparticles as a magnetic engine enhanced the kinetic power and provided control over the direction of movement. Inherent pH-responsive drug release behavior was observed owing to the acidic decomposition of drug carriers in the intracellular microenvironment of cancer cells. This system displayed enhanced anticancer efficacy owing to the synergetic therapeutic strategies and increased cellular uptake in a targeted area because of the improved motion behavior provided by the double engines. Therefore, the demonstrated micromotors are promising candidates for anticancer biomedical microsystems.

ß-Cyclodextrin-grafted hyaluronic acid as a supramolecular polysaccharide carrier for cell-targeted drug delivery.

ß-Cyclodextrin (ß-CD) was grafted onto hyaluronic acid (HA) in a single step to generate a supramolecular biopolymer (HA-ß-CD) that was explored for targeted drug delivery applications. Along with its excellent biocompatibility, the prepared HA-ß-CD exhibits not only exceptionally high loading capacity for the model drugs doxorubicin and Rhodamine B through the formation of inclusion complexes with the ß-CD component, but also the capability of targeted drug delivery to cancerous cells with a high level of expression of CD44 receptors, attributable to its HA component. The polymer can release the drug under slightly acidic conditions. With all its attributes, HA-ß-CD may be a promising cancer-cell-targeting drug carrier.

Conjugated Polymer Nanoparticles Based on Copper Coordination for Real-Time Monitoring of pH-Responsive Drug Delivery.

Metal coordination-driven composite systems have excellent stability and pH-responsive ability, making them suitable for specific drug delivery in physiological conditions. In this study, an anionic conjugated polymer PPEIDA with a poly(p-phenylene ethynylene) backbone and iminodiacetic acid (IDA) side chains is used as a drug carrier to construct a class of pH-responsive nanoparticles, PPEIDA-Cu-DOX conjugated polymer nanoparticles (CPNs), by taking advantage of the metal coordination interaction of Cu2+ with PPEIDA and the drug doxorubicin (DOX). PPEIDA-Cu-DOX CPNs have high drug loading and encapsulation efficiency (EE), calculated to be 54.30 ± 1.10 and 95.80 ± 0.84%, respectively. Due to the good spectral overlap, Förster resonance energy transfer (FRET) takes place between PPEIDA and the drug DOX, which enables the observation of the loading and the release of DOX from CPNs in an acidic environment by monitoring fluorescence emission changes. Therefore, PPEIDA-Cu-DOX CPNs can also be used in real-time cell imaging to monitor drug release in addition to delivering DOX targeting tumor cells. Compared with free DOX, PPEIDA-Cu-DOX CPNs show a similar inhibition to tumor cells and lower toxicity to normal cells. Our results demonstrate the feasibility and potential of constructing pH-responsive CPNs via metal-ligand coordination interactions for cancer treatment.

A dual-targeting Fe3O4@C/ZnO-DOX-FA nanoplatform with pH-responsive drug release and synergetic chemo-photothermal antitumor in vitro and in vivo.

Designing a proper intelligent platform to target cancer cells accurately and reducing its toxic side effects on normal tissues remain a challenge in medicine application. Herein, a novel dual-targeted and tumor microenvironment-triggered Fe3O4@carbon(C)/ZnO-doxorubicin (DOX) -folic acid (FA) drug delivery system with porous structure was designed and fabricated for the first time. The co-presence of Fe3O4 core and FA molecules functioned successfully could successfully realize the magnetic targeting and cancer cell-specific targeting. In addition, pH-responsive ZnO and porous carbon both derived directly from zinc-2-methylimidazolate complex (Zn-ZIF) could play the roles of "gatekeeper" and photothermal agent, respectively. The former could efficiently block the drug within mesoporous in blood environment for decreasing the damage to the normal tissues and achieving the controlled DOX release in the simulated and real acidic tumor microenvironment. And the latter could exhibit the intrinsic photothermal conversion efficiency upon 638 nm laser irradiation. Therefore, the Fe3O4@C/ZnO-DOX-FA nanoplatform integrated dual targeting, controlled chemotherapy with photothermal therapy (PTT) for cancer, displaying a significantly superior synergistic anticancer efficiency both in vitro and in vivo experiments to either monotherapy. Above results suggested the prepared nanoplatforms might be a promising candidate for effectively synergetic therapeutics to cancers.

Gemcitabine-Loaded Magnetically Responsive Poly(ε-caprolactone) Nanoparticles against Breast Cancer.

A reproducible and efficient interfacial polymer disposition method has been used to formulate magnetite/poly(ε-caprolactone) (core/shell) nanoparticles (average size ≈ 125 nm, production performance ≈ 90%). To demonstrate that the iron oxide nuclei were satisfactorily embedded within the polymeric solid matrix, a complete analysis of these nanocomposites by, e.g., electron microscopy visualizations, energy dispersive X-ray spectroscopy, Fourier-transform infrared spectroscopy, electrophoresis, and contact angle goniometry was conducted. The magnetic responsive behaviour of these nanoparticles was quantitatively characterized by the hysteresis cycle and qualitatively investigated by visualization of the colloid under exposure to a 0.4 T magnet. Gemcitabine entrapment into the polymeric shell reported adequate drug loading values (≈11%), and a biphasic and pH-responsive drug release profile (≈ four-fold faster Gemcitabine release at pH 5.0 compared to pH 7.4). Cytotoxicity studies in MCF-7 human breast cancer cells proved that the half maximal inhibitory concentration of Gem-loaded nanocomposites was ≈ two-fold less than that of the free drug. Therefore, these core/shell nanoparticles could have great possibilities as a magnetically targeted Gemcitabine delivery system for breast cancer treatment.

Carbon Nano-Onions Reinforced Multilayered Thin Film System for Stimuli-Responsive Drug Release.

Herein, poly (N-(4-aminophenyl) methacrylamide))-carbon nano-onions (PAPMA-CNOs = f-CNOs) and anilinated-poly (ether ether ketone) (AN-PEEK) have synthesized, and AN-PEEK/f-CNOs composite thin films were primed via layer-by-layer (LbL) self-assembly for stimuli-responsive drug release. The obtained thin films exhibited pH-responsive drug release in a controlled manner; pH 4.5 = 99.2% and pH 6.5 = 59.3% of doxorubicin (DOX) release was observed over 15 days. Supramolecular π-π stacking interactions between f-CNOs and DOX played a critical role in controlling drug release from thin films. Cell viability was studied with human osteoblast cells and augmented viability was perceived. Moreover, the thin films presented 891.4 ± 8.2 MPa of the tensile strength (σult), 43.2 ± 1.1 GPa of Young's modulus (E), and 164.5 ± 1.7 Jg-1 of toughness (K). Quantitative scrutiny revealed that the well-ordered aligned nanofibers provide critical interphase, and this could be responsible for augmented tensile properties. Nonetheless, a pH-responsive and mechanically robust biocompatible thin-film system may show potential applications in the biomedical field.

Rational design and engineering of carbon nano-onions reinforced natural protein nanocomposite hydrogels for biomedical applications.

In the current study, poly 4-hydroxyphenyl methacrylate-carbon nano-onions (PHPMA-CNOs = f-CNOs) are synthesized and reinforced with natural protein gelatin (GL) to engineer GL/f-CNOs composite hydrogels under the sonochemical method. The influence of f-CNOs content on the mechanical properties of hydrogels is examined. Cytotoxicity of hydrogels is measured with the human osteoblast cells. The results revealed good cell viability, cell growth, and attachment on the surface of the hydrogels, and results are f-CNOs dose-dependent. Specifically, the GL/f-CNOs (2 mg/mL) hydrogel showed the highest cell viability, enhanced tensile strength, elastic modulus, and yield strength as compared to pristine GL and GL/f-CNOs (1 mg/mL) hydrogels. It reveals the extent of physisorption and degree of colloidal stability of f-CNOs within the gel matrix. Furthermore, GL/f-CNOs hydrogels efficiently load the 5-fluorouracil (5-FU) and show a pH-responsive sustained drug release over 15 days. Nevertheless, these CNOs based composite hydrogels offer a potential prospect to use them in diverse biomedical applications.