Magnetic and Thermal-sensitive Poly(<em>N</em>-isopropylacrylamide)-based Microgels for Magnetically Triggered Controlled Release

Magnetically and thermally sensitive poly(N-isopropylacrylamide) (PNIPAAm)/Fe3O4-NH2 microgels with the encapsulated anti-cancer drug curcumin (Cur) were ...

Bandung Institute of Technology and Science

Nanoscaled polymer composites were prepared from polysaccharide chitosan (CS) and Ca-deficient hydroxyapatite (CDHA). CS-CDHA nanocomposites were synthesized by in situ precipitation at pH 9, and the CS-CDHA carriers were then fabricated by ionic cross-linking methods using tripolyphosphate and chemical cross-linking methods by glutaraldehyde and genipin. Certain biomolecules such as vitamin B12, cytochrome c, and bovine serum albumin were loaded into the CS-CDHA carriers, and their release behaviors were investigated. Furthermore, these CS-CDHA carriers were examined by transmission electron microscopy, electron spectroscopy for chemical analysis, and X-ray diffraction. The release behavior of the biomolecules was controlled by the CS/CDHA ratios and cross-linked agents. By increasing the concentration of CS and the concentration of the cross-linking agents, cross-linking within carriers increases, and the release rate of the biomolecules is decreased. Moreover, the release rate of the biomolecules from the CS-CDHA carriers at pH 4 was higher than that at pH 10, displaying a pH-sensitive behavior. Therefore, these CS-CDHA hydrogel beads may be useful for intelligent drug release and accelerate bone reconstruction.

Nanohybrid structure analysis and biomolecule release behavior of polysaccharide-CDHA drug carriers.

In this study, we developed the cancer treatment through the combination of chemotherapy and thermotherapy using doxorubicin-loaded magnetic liposomes. The citric acid-coated magnetic nanoparticles (CAMNP, ca. 10 nm) and doxorubicin were encapsulated into the liposome (HSPC/DSPE/cholesterol = 12.5:1:8.25) by rotary evaporation and ultrasonication process. The resultant magnetic liposomes (ca. 90 to 130 nm) were subject to characterization including transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray diffraction (XRD), zeta potential, Fourier transform infrared (FTIR) spectrophotometer, and fluorescence microscope. In vitro cytotoxicity of the drug carrier platform was investigated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using L-929 cells, as the mammalian cell model. In vitro cytotoxicity and hyperthermia (inductive heating) studies were evaluated against colorectal cancer (CT-26 cells) with high-frequency magnetic field (HFMF) exposure. MTT assay revealed that these drug carriers exhibited no cytotoxicity against L-929 cells, suggesting excellent biocompatibility. When the magnetic liposomes with 1 μM doxorubicin was used to treat CT-26 cells in combination with HFMF exposure, approximately 56% cells were killed and found to be more effective than either hyperthermia or chemotherapy treatment individually. Therefore, these results show that the synergistic effects between chemotherapy (drug-controlled release) and hyperthermia increase the capability to kill cancer cells.

Magnetic liposomes for colorectal cancer cells therapy by high-frequency magnetic field treatment.

In the present work, we prepare thermo- and pH-sensitive polymer-based nanoparticles incorporating with magnetic iron oxide as the remote-controlled, stimuli-response nanocarriers. Well-defined, dual functional tri-block copolymer poly[(acrylic acid)-block-(N-isopropylacrylamide)-block-(acrylic acid)], was synthesized via reversible addition-fragmentation chain-transfer (RAFT) polymerization with S,S'-bis(α,α'-dimethyl-α″-acetic acid)trithiocarbonate (CMP) as a chain transfer agent (CTA). With the aid of using 3-aminopropyltriethoxysilane, the surface-modified iron oxides, Fe3O4-NH2, was then attached on the surface of self-assembled tri-block copolymer micelles via 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride/N-hydroxysuccinamide (EDC/NHS) crosslinking method in order to furnish not only the magnetic resources for remote control but also the structure maintenance for spherical morphology of our nanocarriers. The nanocarrier was characterized by transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FT-IR), and ultraviolet-visible (UV/Vis) spectral analysis. Rhodamine 6G (R6G), as the modeling drugs, was encapsulated into the magnetic nanocarriers by a simple swelling method for fluorescence-labeling and controlled release monitoring. Biocompatibility of the nanocarriers was studied via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, which revealed that neither the pristine nanocarrier nor the R6G-loaded nanocarriers were cytotoxic to the normal fibroblast cells (L-929 cells). The in vitro stimuli-triggered release measurement showed that the intelligent nanocarriers were highly sensitive to the change of pH value and temperature rising by the high-frequency magnetic field (HFMF) treatment, which provided the significant potential to apply this technology to biomedical therapy by stimuli-responsive controlled release.

Self-assembly behaviors of thermal- and pH- sensitive magnetic nanocarriers for stimuli-triggered release.

In this research, graphene nanosheets were functionalized with cationic poly (diallyldimethylammonium chloride) (PDDA) and citrate-capped gold nanoparticles (AuNPs) for surface-enhanced Raman scattering (SERS) bio-detection application. AuNPs were synthesized by the traditional citrate thermal reduction method and then adsorbed onto graphene-PDDA nanohybrid sheets with electrostatic interaction. The nanohybrids were subject to characterization including X-ray diffraction (XRD), transmission electron microscopy (TEM), zeta potential, and X-ray photoelectron spectroscopy (XPS). The results showed that the diameter of AuNPs is about 15-20 nm immobilized on the graphene-PDDA sheets, and the zeta potential of various AuNPs/graphene-PDDA ratio is 7.7-38.4 mV. Furthermore, the resulting nanohybrids of AuNPs/graphene-PDDA were used for SERS detection of small molecules (adenine) and microorganisms (Staphylococcus aureus), by varying the ratios between AuNPs and graphene-PDDA. AuNPs/graphene-PDDA in the ratio of AuNPs/graphene-PDDA = 4:1 exhibited the strongest SERS signal in SERS detection of adenine and S. aureus. Thus, it is promising in the application of rapid and label-free bio-detection of bacteria or tumor cells.

Fabrication of Gold Nanoparticles/Graphene-PDDA Nanohybrids for Bio-detection by SERS Nanotechnology.

In this study, multifunctional hybrid nanoparticles composed of iron platinum (FePt), silica (SiO2), and gold nanoparticles (AuNPs) had been developed for surface-enhanced Raman scattering (SERS) application. Core-shell structure of SiO2 and FePt nanoparticles (FePt@SiO2) was fabricated through sol-gel process and then immobilized gold nanoparticles onto the surface of FePt@SiO2, which displays huge Raman enhancement effect and magnetic separation capability. The resulting core-shell nanoparticles were subject to evaluation by transmission electron microscopy (TEM), Energy-dispersive X-ray spectroscopy (EDX), zeta potential measurement, and X-ray photoelectron spectroscopy (XPS). TEM observation revealed that the particle size of resultant nanoparticles displayed spherical structure with the size ~30 nm and further proved the successful immobilization of Au onto the surface of FePt@SiO2. Zeta potential measurement exhibited the successful reaction between FePt@SiO2 and AuNPs. The rapid SERS detection and identification of small biomolecules (adenine) and microorganisms (gram-positive bacteria, Staphylococcus aureus) was conducted through Raman spectroscopy. In summary, the novel core-shell magnetic nanoparticles could be anticipated to apply in the rapid magnetic separation under the external magnetic field due to the core of the FePt superparamagnetic nanoparticles and label-free SERS bio-sensing of biomolecules and bacteria.

Core-shell of FePt@SiO2-Au magnetic nanoparticles for rapid SERS detection.

Magnetic silica core/shell nanovehicles presenting atherosclerotic plaque-specific peptide-1 (AP-1) as a targeting ligand (MPVA-AP1 nanovehicles) have been prepared through a double-emulsion method and surface modification. Amphiphilic poly(vinyl alcohol) was introduced as a polymer binder to encapsulate various drug molecules (hydrophobic, hydrophilic, polymeric) and magnetic iron oxide (Fe3O4) nanoparticles. Under a high-frequency magnetic field, magnetic carriers (diameter: ca. 50 nm) incorporating the anti-cancer drug doxorubicin collapsed, releasing approximately 80% of the drug payload, due to the heat generated by the rapidly rotating Fe3O4 nanoparticles, thereby realizing rapid and accurate controlled drug release. Simultaneously, the magnetic Fe3O4 themselves could also kill the tumor cells through a hyperthermia effect (inductive heating). Unlike their ungrafted congeners (MPVA nanovehicles), the AP1-grafted nanovehicles bound efficiently to colorectal cancer cells (CT26-IL4Rα), thereby displaying tumor-cell selectivity. The combination of remote control, targeted dosing, drug-loading flexibility, and thermotherapy and chemotherapy suggests that magnetic nanovehicles such as MPVA-AP1 have great potential for application in cancer therapy.

Magnetically triggered nanovehicles for controlled drug release as a colorectal cancer therapy.

Less targeted and limited solubility of hydrophobic-based drug are one of the serious obstacles in drug delivery system. Thus, new strategies to enhance the solubility of hydrophobic drug and controlled release behaviors would be developed. Herein, curcumin, a model of hydrophobic drug, has been loaded into PEGylated magnetic liposomes as a drug carrier platform for drug controlled release system. Inductive magnetic heating (hyperthermia)-stimulated drug release, in vitro cellular cytotoxicity assay of curcumin-loaded PEGylated magnetic liposomes and cellular internalization-induced by magnetic guidance would be investigated. The resultant of drug carriers could disperse homogeneously in aqueous solution, showing a superparamagnetic characteristic and could inductive magnetic heating with external high-frequency magnetic field (HFMF). In vitro curcumin release studies confirmed that the drug carriers exhibited no significant release at 37 °C, whereas exhibited rapid releasing at 45 °C. However, it would display enormous (three times higher) curcumin releasing under the HFMF exposure, compared with that without HFMF exposure at 45 °C. In vitro cytotoxicity test shows that curcumin-loaded PEGylated magnetic liposomes could efficiently kill MCF-7 cells in parallel with increasing curcumin concentration. Fluorescence microscopy observed that these drug carriers could internalize efficiently into the cellular compartment of MCF-7 cells. Thus, it would be anticipated that the novel hydrophobic drug-loaded PEGylated magnetic liposomes in combination with inductive magnetic heating are promising to apply in the combination of chemotherapy and thermotherapy for cancer therapy.

Andri Hardiansyah

Department of Metallurgy and Materials Engineering

Bandung Institute of Technology and Science

Magnetic and Thermal-sensitive Poly(N-isopropylacrylamide)-based Microgels for Magnetically Triggered Controlled Release

Andri Hardiansyah

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Metallurgy and Materials Engineering

Bandung Institute of Technology and Science

Magnetic and Thermal-sensitive Poly(N-isopropylacrylamide)-based Microgels for Magnetically Triggered Controlled Release

Department of Metallurgy and Materials Engineering