Synthesis of Silica-Coated Magnetic Hydroxyapatite Composites for Drug Delivery Applications.

We have prepared a core-shell magnetic silica-coated hydroxyapatite, Fe3O4@SiO2@HAp composite materials for pH-responsive drug delivery applications. Captopril (Cap) and ibuprofen (Ibu) were chosen as model hydrophilic and hydrophobic drugs, respectively. The drugs were encapsulated into the Fe3O4@SiO2@HAp composite via electrostatic interactions with existing amine and carboxylic acid groups during calcium phosphate shell formation. The formation of calcium phosphate shell not only protects the encapsulated drugs from leaching but also controls the release rate of drugs from the composite system depending on various pH conditions. We have tested the release behavior of Cap and Ibu drugs under different pH conditions such as neutral pH (pH 7.4) and acidic pH (pH 5.0), respectively. The study result reveals that the synthesized Fe3O4@SiO2@HAp composite is suitable for release of both water soluble and water insoluble drugs based on a pH-responsive controlled manner.

Anti-EGFR Antibody Conjugation of Fucoidan-Coated Gold Nanorods as Novel Photothermal Ablation Agents for Cancer Therapy.

The development of novel photothermal ablation agents as cancer nanotheranostics has received a great deal of attention in recent decades. Biocompatible fucoidan (Fu) is used as the coating material for gold nanorods (AuNRs) and subsequently conjugated with monoclonal antibodies against epidermal growth factor receptor (anti-EGFR) as novel photothermal ablation agents for cancer nanotheranostics because of their excellent biocompatibility, biodegradability, nontoxicity, water solubility, photostability, ease of surface modification, strongly enhanced absorption in near-infrared (NIR) regions, target specificity, minimal invasiveness, fast recovery, and prevention of damage to normal tissues. Anti-EGFR Fu-AuNRs have an average particle size of 96.37 ± 3.73 nm. Under 808 nm NIR laser at 2 W/cm2 for 5 min, the temperature of the solution containing anti-EGFR Fu-AuNRs (30 µg/mL) increased by 52.1 °C. The anti-EGFR Fu-AuNRs exhibited high efficiency for the ablation of MDA-MB-231 cells in vitro. In vivo photothermal ablation exhibited that tumor tissues fully recovered without recurrence and finally were reconstructed with normal tissues by the 808 nm NIR laser irradiation after injection of anti-EGFR Fu-AuNRs. These results suggest that the anti-EGFR Fu-AuNRs would be novel photoablation agents for future cancer nanotheranostics.

Multifunctional biocompatible chitosan-polypyrrole nanocomposites as novel agents for photoacoustic imaging-guided photothermal ablation of cancer.

Cancer nanotechnology is emerging as one of the promising strategies combining photothermal therapy (PTT) and photoacoustic imaging (PAI) for the treatment of breast cancer and it has received considerable attention in the recent years because it is minimally invasive, prevents damage to non-targeted regions, permits fast recovery, and involves breast cancer imaging. The present study demonstrates multifunctional biocompatible chitosan-polypyrrole nanocomposites (CS-PPy NCs) as novel agents for photoacoustic imaging-guided photothermal ablation of cancer because of their biocompatibility, conductivity, stability, and strong near-infrared (NIR) absorbance. The CS-PPy NCs are spherical in shape and range 26-94 nm in size with a mean value of 50.54 ± 2.56 nm. The in vitro results demonstrated good biocompatibility of CS-PPy NCs, which can be used in PTT for cancer cells under 808-nm NIR laser irradiation. Tumor-bearing mice fully recovered after treatment with CS-PPy NCs and NIR 808-nm laser irradiation compared to the corresponding control groups. Our research highlights the promising potential of using CS-PPy NCs for photoacoustic imaging-guided photothermal ablation of cancer in preclinical animals, which should be verified in future clinical trials.

Astaxanthin conjugated polypyrrole nanoparticles as a multimodal agent for photo-based therapy and imaging.

Polymeric nanoparticles are emerging as promising candidates for photo-based therapy and imaging due to their versatile chemical properties and easy fabrication and functionalization. In the present study we synthesized polypyrrole nanoparticles by stabilization with astaxanthin conjugated bovine serum albumin polymer (PPy@BSA-Astx). The synthesized nanoparticles were biocompatible with MBA-MD-231 and HEK-293 cells. Interestingly, the fabricated nanoparticles produced reactive oxygen species under 808-nm laser exposure and exerted a hyperthermic effect when the power density of the laser was increased. The photodynamic efficiency of PPy@BSA-Astx was measured by DPBF assay, and it was found to generate sufficient amount of reactive radicals to kill the cells at a power density of 0.3W/cm2. In photothermal aspect, the temperature level was reached to 57°C within 5min at 1W/cm2 power density, at the concentration of 50µg/mL. The in vitro cell toxicity studies showed concentration dependent photothermal and photodynamic toxicity. Fluorescence microscopic investigation explored the cell death and intra-cellular organ destruction by photodynamic treatment. In addition, we observed a strong photoacoustic signal from a tissue mimicking phantom study of nanoparticle treated MBA-MD-231 cells. In conclusion, the fabricated PPy@BSA-Astx nanoparticles can be used as photoacoustic imaging based prognostic agents for photothermal or photodynamic treatment.

Doxorubicin-loaded fucoidan capped gold nanoparticles for drug delivery and photoacoustic imaging.

Polymer nanoparticles are emerging as a useful tool for a wide variety of biomedical and therapeutic applications. The present study demonstrates the multifunctional doxorubicin-loaded fucoidan capped gold nanoparticles (DOX-Fu AuNPs) for drug delivery and photoacoustic imaging (PAI). Biocompatible AuNPs were synthesized using a naturally occurring fucoidan (Fu) as a capping and reducing agent. The Fu AuNPs synthesis was determined using UV-visible spectrum, and it was further characterized using high resolution transmission electron microscopy, energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, and X-ray diffraction analysis. The release of DOX from DOX-Fu AuNPs was greater in acidic pH (4.5) than in neutral pH (7.4). The in vitro cytotoxic effect of fucoidan, Fu AuNPs, DOX, and DOX-Fu AuNPs inhibited the proliferation of human breast cancer cells with an inhibitory concentration of 35µg/mL, 30µg/mL, 15µg/mL, and 5µg/mL at 24h. DOX-Fu AuNPs induced both early and late apoptosis in a concentration-dependent manner compared with untreated control cells. The ability of DOX-Fu AuNPs as a contrast agent for in vitro breast cancer imaging with PAI has been evaluated. These results suggest that the multifunctional DOX-Fu AuNPs for drug delivery and PAI can soon provide considerable contribution to human health.

Cytotoxic Induction and Photoacoustic Imaging of Breast Cancer Cells Using Astaxanthin-Reduced Gold Nanoparticles.

Astaxanthin, a kind of photosynthetic pigment, was employed for gold nanoparticle formation. Nanoparticles were characterized using Ulteraviolet-Visible (UV-Vis) spectroscopy, transmission electron microscopy, and X-ray diffraction, and the possible presence of astaxanthin functional groups were analyzed by Fourier transform infrared spectroscopy (FTIR). The cytotoxic effect of synthesized nanoparticles was evaluated against MDA-MB-231 (human breast cancer cells) using a tetrazolium-based assay, and synthesized nanoparticles exhibited dose-dependent toxicity. The morphology upon cell death was differentiated through fluorescent microscopy using different stains that predicted apoptosis. The synthesized nanoparticles were applied in ultrasound-coupled photoacoustic imaging to obtain good images of treated cells. Astaxanthin-reduced gold nanoparticle has the potential to act as a promising agent in the field of photo-based diagnosis and therapy.

Intravascular ultrasonic-photoacoustic (IVUP) endoscope with 2.2-mm diameter catheter for medical imaging.

Intravascular ultrasound (IVUS) imaging is extremely important for detection and characterization of high-risk atherosclerotic plaques as well as gastrointestinal diseases. Recently, intravascular photoacoustic (IVPA) imaging has been used to differentiate the composition of biological tissues with high optical contrast and ultrasonic resolution. The combination of these imaging techniques could provide morphological information and molecular screening to characterize abnormal tissues, which would help physicians to ensure vital therapeutic value and prognostic significance for patients before commencing therapy. In this study, integration of a high-frequency IVUS imaging catheter (45MHz, single-element, unfocused, 0.7mm in diameter) with a multi-mode optical fiber (0.6mm in core diameter, 0.22 NA), an integrated intravascular ultrasonic-photoacoustic (IVUP) imaging catheter, was developed to provide spatial and functional information on light distribution in a turbid sample. Simultaneously, IVUS imaging was co-registered to IVPA imaging to construct 3D volumetric sample images. In a phantom study, a polyvinyl alcohol (PVA) tissue-mimicking arterial vessel phantom with indocyanine green (ICG) and methylene blue (MB) inclusion was used to demonstrate the feasibility of mapping the biological dyes, which are used in cardiovascular and cancer diagnostics. For the ex vivo study, an excised sample of pig intestine with ICG was utilized to target the biomarkers present in the gastrointestinal tumors or the atherosclerotic plaques with the proposed hybrid technique. The results indicated that IVUP endoscope with the 2.2-mm diameter catheter could be a useful tool for medical imaging.