Magnetic graphene oxide functionalized alginate-g-poly(2-hydroxypropylmethacrylamide) nanoplatform for near-infrared light/pH/magnetic field-sensitive drug release and chemo/phototherapy.

Multifunctional nanoplatforms developed from natural polymers and graphene oxide (GO) with enhanced biological/physicochemical features have recently attracted attention in the biomedical field. Herein, a new multifunctional near-infrared (NIR) light-, pH- and magnetic field-sensitive hybrid nanoplatform (mGO@AL-g-PHPM@ICG/EP) is developed by combining iron oxide decorated graphene oxide nanosheets (mGO) and poly(2-hydroxypropylmethacrylamide) grafted alginate (AL-g-PHPM) copolymer loaded with indocyanine green (ICG) and etoposide (EP) for chemo/phototherapy. The functional groups, specific crystal structure, size, morphology, and thermal stability of the nanoplatform were fully characterized by XRD, UV, FTIR, AFM/TEM/FE-SEM, VSM, DSC/TG, and BET analyses. In this platform, the mGO and ICG, as phototherapeutic agents, demonstrate excellent thermal effects and singlet oxygen production under NIR-light (808 nm) irradiation. The XRD and DSC analysis confirmed the amorphous state of the ICG/EP in the nanoparticles. In vitro photothermal tests proved that the mGO@AL-g-PHPM@ICG/EP nanoparticles had outstanding light stability and photothermal conversion ability. The in vitro release profiles presented NIR light-, pH- and magnetic field-controlled EP/ICG release behaviors. In vitro experiments demonstrated the excellent antitumor activity of the mGO@AL-g-PHPM@ICG/EP against H1299 tumor cells under NIR laser. Benefiting from its low-cost, facile preparation, and good dual-modal therapy, the mGO@AL-g-PHPM@ICG/EP nanoplatform holds great promise in multi-stimuli-sensitive drug delivery and chemo/phototherapy.

Design and development of pH-responsive alginate-based nanogel carriers for etoposide delivery.

Recently, pH-responsive nanogels are playing progressively important roles in cancer treatment. The present study focuses on designing and developing pH-responsive alginate-based nanogels to achieve a controlled release of etoposide (Et) while enhancing its hydrophilicity. Alginate (ALG) is grafted with 2-hydroxypropyl methacrylamide (HPMA) through a microwave-supported method, and the chemical structure of the graft copolymer (ALG-g-PHPMA) was verified by 1H/13C NMR and FTIR techniques. The ALG-g-PHPMA and anticancer drug-loaded ALG-g-PHPMA@Et nanogels were obtained using an emulsion method, and their structures were characterized through FTIR, TG/DSC, AFM/TEM, BET, and DLS analyses. The ALG-g-PHPMA nanogels demonstrated a good drug encapsulation efficiency (79.60 %), displaying a pH-dependent release profile and an in vitro accelerated release of Et compared to the ALG nanogels. Thermal and BET analyses revealed enhanced stability, surface area, and porosity volume of the alginate nanogels. The grafting of PHPMA chains onto alginate altered the surface topology of the ALG nanogels, resulting in lower surface roughness. Furthermore, cytotoxicity tests showed the high biocompatibility of the ALG-g-PHPMA copolymer and its nanogels. The ALG-g-PHPMA@Et nanogels exhibited a higher anticancer effect on lung cancer (H1299) cells than free etoposide. These results suggest that the ALG-g-PHPMA nanogels can be applied as a pH-dependent nanoplatform for delivering anticancer drugs.

Preparation, characterization, and evaluation of antibacterial and cytotoxic activity of chitosan-polyethylene glycol nanoparticles loaded with amoxicillin as a novel drug delivery system.

In this study, nanoparticles of amoxicillin (AMX) were prepared using chitosan (CHI) and polyethylene glycol (PEG). The physicochemical properties of the particles were investigated by FT-IR, DSC, SEM, and zeta potential analyses. The nanoparticles showed a spherical shape, and the average size of formulations was within the range of 696.20 ± 24.86 - 359.53 ± 7.41 nm. Zeta potential data demonstrated that the formulations had positive surface charges with a zeta potential range of 21.38 ± 2.28 - 7.73 ± 1.66 mV. FTIR analysis showed that the drug was successfully entrapped in the nanoparticles. DSC results suggested that the drug was present in amorphous form in the polymer matrix. In vitro release studies demonstrated that the release pattern consisted of two phases, with an initial burst release followed by a controlled and sustained release. The MTT assay results on mouse fibroblast cell line indicated that the prepared formulations did not affect the viability of the cells. In the in vitro antibacterial activity test, it was found that the drug-loaded nanoparticles have AMX-equivalent antibacterial activity against E. coli, and S. aureus. These findings revealed that the obtained nanoparticles might be a promising and safe nanocarrier system for efficient delivery of AMX.

Amoxicillin has been encapsulated in PEG-CHI nanoparticles.The structure of nanoparticles was investigated by SEM, FTIR, and DSC studies.The nanoparticles showed an initial fast release followed by a slow release.PEG-CHI nanoparticles displayed equivalent antibacterial activity to amoxicillin, and a non-cytotoxic profile in healthy cells.

Design and fabrication of hybrid triple-responsive κ-carrageenan-based nanospheres for controlled drug delivery.

In the last two decades, the utilization of magnetic nanospheres in intelligent polymeric structures have received increased attention of researchers in numerous biomedical applications. Here, hybrid nanostructured triple-responsive magnetic nanospheres (κ-Car-g-P(AA/DMA)@Fe3O4) containing inorganic iron oxide core (Fe3O4) and organic graft copolymeric shell based on κ-carrageenan (κ-Car) and poly(acrylic acid/dimethylaminoethyl methacrylate) (P(AA/DMA)) were synthesized by microwave induced co-precipitation technique. The structure, size, surface morphology, magnetic property and stability of synthesized κ-Car-g-P(AA/DMA)@Fe3O4 magnetic nanospheres were characterized using FTIR, UV, XRD, TEM, Zeta-sizer, and VSM. κ-Car-g-P(AA/DMA)@Fe3O4 nanospheres were loaded with 5-Fluorouracil (5-FU) as an antineoplastic drug, and their 5-FU release behavior was explored in diverse graft yields, pH values, temperatures and in the existence of an alternating magnetic field. The κ-Car-g-P(AA/DMA)@Fe3O4 nanospheres demonstrated pH-, thermo-, and magnetic field-responsive 5-FU release with good biocompatibility and excellent anticancer activity. In addition, 5-FU release under 50 mT magnetic field reached to 100% within 4 h. This work exhibits that hybrid nanospheres have a triple stimuli-responsive influence, which is of principal importance for the future design and application of multi-functional responsive platforms to develop externally stimulated release of active agents and their healthcare capability.

Synthesis and characterization of thermo/pH-sensitive pectin-graft-poly(dimethylaminoethyl methacrylate) coated magnetic nanoparticles.

Herein, thermo- and pH-sensitive pectin-graft-poly(dimethylaminoethyl methacrylate) copolymer-coated magnetic nanoparticles were synthesized via a green and rapid synthetic approach based on microwave irradiation. Firstly, a novel thermo- and pH-sensitive pectin-graft-poly(dimethylaminoethyl methacrylate) copolymer (Pec-g-PolyDMAEMA) was synthesized and then, Pec-g-PolyDMAEMA based magnetic nanoparticles (Pec-g-PolyDMAEMA@Fe3O4) were produced via microwave-assisted co-precipitation method. The thermo/pH/magnetic field multi-sensitive hybrid nanoparticle was characterized by techniques like TEM, VSM, FT-IR, and TGA/DSC. In vitro release studies of 5-Fluorouracil (FL) were carried out by altering the temperature (37 and 44°C), pH (5.5 and 7.4) and presence of an AMF. The FL release of Pec-g-PolyDMAEMA@Fe3O4@FL exhibited pH-sensitive behavior. They showed thermo/pH-sensitive FL release features with the greatest release of FL at 37°C (56%) than at 44°C (40%) and at pH of 7.4 (63%) than at pH of 5.5 (45%) within 48h. The FL release was also significantly increased (100%) with the presence of a 50 mT magnetic field. These results indicate that the developed Pec-g-PolyDMAEMA@Fe3O4 nanoparticles are promising in the application of multi-stimuli-sensitive delivery of drugs.

Pectin-conjugated magnetic graphene oxide nanohybrid as a novel drug carrier for paclitaxel delivery.

Recent studies have shown that graphene oxide (GO) drug carrier functionalized with biocompatible natural polymers lead to higher loading efficacy and better stability with diminished cellular toxicity. Pectin (PEC) is one of the polysaccharide natural polymers, which has the potential to be used for drug delivery. In this work, we have successfully developed a novel PEC-conjugated magnetic GO nanocarrier for effective delivery of paclitaxel. The structure, surface morphology and thermal stability of the nanohybrid were investigated using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), transmission electron microscopy (TEM) and zeta-sizer. Moreover, drug loading and release performance were studied by UV-vis absorption spectra. The cytotoxicity test was also performed by MTT test using L-929 fibroblast normal cell and MCF-7 cancer lines. The prepared nanocarrier showed an improved stability with enhanced drug loading capacity. Additionally, pH-responsive release analysis of the nanohybrid illustrated higher drug release at endosomal pH of cancer cell than that of normal physiological environment. Besides, cytotoxicity test demonstrated the synthesized nanohybrid is biocompatible, having very high relative cell viability. Bearing in mind these findings, the designed multifunctional nanohybrid drug carrier will be a good candidate for cancer drug delivery.

ICG-conjugated Magnetic Graphene Oxide for Dual Photothermal and Photodynamic Therapy.

Aptamer-functionalized magnetic graphene oxide conjugates loaded with indocyanine green (ICG) dye, or Apt@ICG@mGO, have been successfully developed for dual-targeted photothermal and photodynamic therapy. In general, a drug or its carrier or their dosage can be imprtant important issues in terms of toxicity. However, in this system, each component used is quite safe, biocompatibe and clean. For instance, ICG, a Food and Drug Administration (FDA) approved near-infrared (NIR) dye, serves as both a photothermal and photodynamic agent. It is immobilized on the surface of mGO via a physical interaction called "π-π stacking". The mGO, as a most biocomptible member of the carbo family, is selected for use as a platform for aptamer and ICG dye conjugation, as well as as a photothermal agent. The light in the near-infrared region (NIR) was chosen as a harmless light source for activating the agents for photothermal therapy (PTT) and photodynamic therapy (PDT). The magnetic properties of mGO are also used for separation of Apt@ICG@mGO conjugates from the reaction medium. Aptamer sgc8 acts as a targeting ligand to selectively and specifically bind to a protein on the membrane of cancer cell line CCRF-CEM. After the aptamer- functionalized ICG@mGO conjugates are incubated with target CEM cells at 37 °C for 2 hours, they are bound to cells or they may be internalized into the cell via endocytosis. More significantly, we demonstrated that the Apt@ICG@mGO conjugates produce heat for photothermal therapy (PTT) and singlet oxygen for photodynamic therapy (PDT) upon NIR laser irradiation at 808 nm. Thus, remarkably efficient cancer cell destructions with ~41% and ~60% and ~82% cell killing using 10, 50 and 100 ppm Apt@ICG@mGO, respectively are achieved in 5 min light exposure.