Madhappan Santha Moorthy

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.

Synthesis of amine-polyglycidol functionalised Fe3O4@SiO2 nanocomposites for magnetic hyperthermia, pH-responsive drug delivery, and bioimaging applications

The combined chemotherapy and thermal therapy is mainly considered in clinical applications in cancer therapy. However, the preparation of multifunctional nanomaterials is an attractive approach for cancer treatment. In this report, we present the synthesis of amine-polyglycidol functional shell modified-silica coated-magnetic iron oxide nanocomposites (Fe3O4@SiO2@APG-F) for a FITC conjugated drug carrier system and/or hyperthermia agent in cancer therapy. The Fe3O4@SiO2@APG-F nanocomposite exhibits superparamagnetic properties with a magnetic saturation value of approximately 17.2 emu g−1. The magnetic hyperthermia experiment shows a very fast temperature increase within a short time (45 °C in 4.5 min) when applying an alternating magnetic field (AMF), which is considered to be an appropriate temperature for the localized hyperthermia treatment in cancer therapy. Further, the fluorescein isothiocyanate (FITC), a model fluoropore, was conjugated with the terminal amine groups of the Fe3O4@SiO2@APG to endow the green fluorescent behavior that may be desirable for biological imaging applications. The Fe3O4@SiO2@APG-F material shows high drug loading efficiency and the MTT assay results evidenced that the synthesised Fe3O4@SiO2@APG-F nanocomposites are biocompatible. The fluorescence microscopic images show the particles can be effectively taken up by cancer cells. Therefore, the FITC conjugated Fe3O4@SiO2@APG-F nanocomposites that possess a magnetic core covered by silica coating, organic APG functional shell, and FITC fluorophore together in a single entity could serve as a good hyperthermia agent, drug delivery carrier, and fluorescent contrast agent for bioimaging. Thus, the Fe3O4@SiO2@APG-F nanocomposite could be considered as a promising material to be used in multimodal cancer therapy.

Chlorin e6 conjugated silica nanoparticles for targeted and effective photodynamic therapy

Photodynamic therapy (PDT) using photosensitizer drug has become an important therapeutic modality. However, the stability and targeted delivery of photosensitizer remain a critical challenge for efficient PDT treatment. In the present study, we developed chlorin e6 (Ce6)-conjugated and folic acid (FA)-decorated silica nanoparticles (silica-Ce6-FA) for targeted delivery of photosensitizer to the cancer cells. The synthesized NPs exhibited excellent stability and biocompatibility with MDA-MB-231 cells. The formulated particles were efficiently taken up by folate receptor-positive MDA-MB-231 cells, which were confirmed by comparative analysis with folate receptor-negative HepG2 cells. The folate receptor-targeted silica-Ce6-FA was highly accumulated inside the MDA-MB-231 cells than free Ce6. The obtained NPs produced singlet oxygen efficiently under 670-nm laser exposure. The cell-killing effect of silica-Ce6-FA was higher when compared with free Ce6 under PDT treatment. The PDT-induced mitochondrial damage and apoptotic cell death were detected in silica-Ce6-FA-treated cells.

pH and NIR-light-responsive magnetic iron oxide nanoparticles for mitochondria-mediated apoptotic cell death induced by chemo-photothermal therapy

Recently, various therapeutic strategies in anticancer drug development are focused to reduce adverse side effects and to enhance the therapeutic efficacy. Mostly, the iron oxide (Fe3O4) nanoparticles have widely been utilized as an efficient drug delivery system towing to their unique properties such as excellent magnetic behavior, considerably low toxicity, easy surface modification and high drug-loading efficacy. In the present study, we synthesized a multifunctional, DMSA coated, water soluble Fe3O4 nanoparticles (Fe3O4@DMSA/DOX) for an effective pH and NIR-light triggered delivery of anticancer drug (DOX) in cancer therapy. The combination of photothermal therapy combined with chemotherapy results demonstrated that the synthesized Fe3O4@DMSA/DOX is an excellent candidate for pH- and NIR-light induced phothothermal agent for an effective delivery of anticancer drug (DOX) into the target sub-cellular level into the human breast cancer (MDA-MB-231) cells. Furthermore, the Fe3O4@DMSA/DOX nanoparticles induced an excellent temperature elevation upon NIR light irradiation and controlled DOX release in vitro. The Fe3O4@DMSA/DOX nanoparticles exhibited synergistic effect when combining chemotherapy with photothermal therapy and showed an excellent cell toxicity to MDA-MB-231 cells. In addition, the combined chemo-photothermal therapy of Fe3O4@DMSA/DOX nanoparticles promoted an effective cell death by mitochondrial disruption mediated by ROS generation. Thus, the synthesized Fe3O4@DMSA/DOX nanoparticles could be utilized as potential anticancer agents for breast cancer treatment.

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.

Marine Biopolymer-Based Nanomaterials as a Novel Platform for Theranostic Applications

ABSTRACT Marine biopolymer-based nanomaterials are one of the most active research areas in recent decades for theranostic applications. Marine biopolymers are interesting biomaterials for clinical applications because of their good biocompatibility, biodegradability, inexpensiveness, abundance, stability, ease of surface modification, and nontoxic nature. New nanoparticles in development are coated with marine polymers to combine therapeutic and diagnostic (theranostic) applications because of the strongly enhanced absorption and scattering in near-infrared (NIR) regions. In this review, the use of marine biopolymer-based nanomaterials for theranostic applications is evaluated, addressing potential applications in drug delivery, photothermal therapy (PTT), photodynamic therapy (PDT), hyperthermia therapy, photoacoustic imaging (PAI), magnetic resonance imaging (MRI), and computed tomography (CT). In addition, the most recent progress in the biocompatibility of marine biopolymer-based nanomaterials in vitro and in vivo are discussed, along with a promising future scope for the treatment of major life-threatening diseases such as cancer.

In Vitro Photodynamic Effect of Phycocyanin against Breast Cancer Cells.

C-phycocyanin, a natural blue-colored pigment-protein complex was explored as a novel photosensitizer for use in low-level laser therapy under 625-nm laser illumination. C-phycocyanin produced singlet oxygen radicals and the level of reactive oxygen species (ROS) were raised in extended time of treatment. It did not exhibit any visible toxic effect in the absence of light. Under 625-nm laser irradiation, c-phycocyanin generated cytotoxic stress through ROS induction, which killed MDA-MB-231 breast cancer cells depending on concentrations. Different fluorescent staining of laser-treated cells explored apoptotic cell death characteristics like the shrinking of cells, cytoplasmic condensation, nuclei cleavage, and the formation of apoptotic bodies. In conclusion, phycocyanin is a non-toxic fluorescent pigment that can be used in low-level light therapy.

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.

In vivo photoacoustic monitoring using 700-nm region Raman source for targeting Prussian blue nanoparticles in mouse tumor model

Photoacoustic imaging (PAI) is a noninvasive imaging tool to visualize optical absorbing contrast agents. Due to high ultrasonic resolution and superior optical sensitivity, PAI can be used to monitor nanoparticle-mediated cancer therapy. The current study synthesized Food and Drug Administration-approved Prussian blue (PB) in the form of nanoparticles (NPs) with the peak absorption at 712 nm for photoacoustically imaging tumor-bearing mouse models. To monitor PB NPs from the background tissue in vivo, we also developed a new 700-nm-region stimulated Raman scattering (SRS) source (pulse energy up to 200 nJ and repetition rate up to 50 kHz) and implemented optical-resolution photoacoustic microscopy (OR-PAM). The SRS-assisted OR-PAM system was able to monitor PB NPs in the tumor model with micrometer resolution. Due to strong light absorption at 712 nm, the developed SRS light yielded a two-fold higher contrast from PB NPs, in comparison with a 532-nm pumping source. The proposed laser source involved cost-effective and simple system implementation along with high compatibility with the fiber-based OR-PAM system. The study highlights the OR-PAM system in conjunction with the tunable-color SRS light source as a feasible tool to assist NP-mediated cancer therapy.

Multimodal tumor-homing chitosan oligosaccharide-coated biocompatible palladium nanoparticles for photo-based imaging and therapy

Palladium, a near-infrared plasmonic material has been recognized for its use in photothermal therapy as an alternative to gold nanomaterials. However, its potential application has not been explored well in biomedical applications. In the present study, palladium nanoparticles were synthesized and the surface of the particles was successfully modified with chitosan oligosaccharide (COS), which improved the biocompatibility of the particles. More importantly, the particles were functionalized with RGD peptide, which improves particle accumulation in MDA-MB-231 breast cancer cells and results in enhanced photothermal therapeutic effects under an 808-nm laser. The RGD peptide-linked, COS-coated palladium nanoparticles (Pd@COS-RGD) have good biocompatibility, water dispersity, and colloidal and physiological stability. They destroy the tumor effectively under 808-nm laser illumination at 2 W cm−2 power density. Further, Pd@COS-RGD gives good amplitude of photoacoustic signals, which facilitates the imaging of tumor tissues using a non-invasive photoacoustic tomography system. Finally, the fabricated Pd@COS-RGD acts as an ideal nanotheranostic agent for enhanced imaging and therapy of tumors using a non-invasive near-infrared laser.