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To achieve optimum functionality and mechanical properties of advanced manufacturing-based scaffolds for biomedical application, it is important to study their mechanical strength by 3D-printing at different orientations. This study examined the effects of printing at different orientations on the mechanical properties of synthesized 3D-polylactic acid (PLA) and hydroxyapatite-modified PLA (PLA-HAp) scaffolds. A total number of 30 samples were printed in three orientations on the XY plane: 0°, 45°, and 90°. Finite element modeling and simulation was employed to identify the strongest scaffold in terms of compression strength, which is the primary criterion for load bearing bone tissue scaffolds. These findings indicate that 3D-printing at an orientation of 90° on the XY plane resulted in a scaffold with the highest compression strength. Moreover, the fabricated PLA scaffolds showed very poor cell attachment and proliferation on their surface, which is not suitable for their biomedical application. This study additionally showed the optimization of a very simple post-fabrication modification technique with nano HAp for better cell attachment and proliferation with enhanced mechanical properties. The post-fabrication modification of PLA scaffolds by nano-HAp results in excellent cell attachment property with enhanced mechanical strength and stability of up to 47.16% for 90° 3D-printed PLA-HAp scaffolds.

Developing a novel multifunctional theranostic agent for cancer combination therapy has attracted tremendous attention in recent years. In this report, we designed and developed a new multifunctional nanocarrier based on anti-epidermal growth factor receptor antibody-conjugated and paclitaxel loaded-thiol chitosan-layered gold nanoshells (anti-EGFR-PTX-TCS-GNSs) as a theranostic agent for the first time used for fluorescence/photoacoustic dual-modal imaging-guided chemophotothermal synergistic therapy. The resulting anti-EGFR-PTX-TCS-GNSs showed excellent biosafety, biocompatibility, broad near-infrared (NIR) absorbance, photostability, fast and laser irradiation-controllable drug release, and higher targeting efficiency for efficient chemophotothermal combination therapy of cancer under the guidance of photoacoustic imaging (PAI). The combination therapy was investigated in vitro and in vivo, displaying a powerful anticancer efficiency. More importantly, an in vivo experiment of anti-EGFR-PTX-TCS-GNSs with laser irradiation showed heavy damage to the tumor tissue, killing the tumor cells almost completely. Anti-EGFR-PTX-TCS-GNSs also showed a powerful capacity to visualize tumors, and therefore it is considered a new PAI contrast agent for subsequent therapy. Histological analysis and TUNEL assay further showed much more apoptotic cells, confirming the value of anti-EGFR-PTX-TCS-GNSs. Our results provide a new concept and a promising strategy to develop a novel multifunctional nanotheranostic agent for future clinical applications in diagnosis and therapy.

Pseudomonas aeruginosa is an opportunistic human pathogen which exhibits its property of pathogenesis due to several factors, including the formation of biofilm and production of several virulence factors. Development of resistance properties against antibiotics leads to the discovery of certain alternative strategies to combat its pathogenesis. In the present study, a highly stable, biocompatible and water soluble nanocomposites (NCs) are synthesized from chitosan (CS) and the polypyrrole (PPy). The resultant chitosan-polypyrrole nanocomposites (CS-PPy NCs) inhibit the establishment of biofilm and also eradicate the preformed matured biofilm formed by P. aeruginosa. CS-PPy NCs inhibit the hemolytic and protease activities of P. aeruginosa. The NCs significantly reduce the production of many virulence factors such as pyocyanin, pyroverdine and rhamnolipid. CS-PPy NCs also suppress the bacterial motility such as swimming and swarming. The present study showed that highly stable CS-PPy NCs act as a potent antibiofilm and antivirulence drug for the treatment of P. aeruginosa infection.

The development of a new generation of multifunctional nanomaterials as a drug delivery system for chemo-photothermal therapy is of great necessity. In this study, we first prepared folic acid-conjugated and doxorubicin-loaded chitosan oligosaccharide encapsulated gold nanorods (FA–COS–TGA–GNRs–DOX) as a new photothermal agent for the delivery of drugs and heat to tumor areas. FA–COS–TGA–GNRs–DOX nanomaterials combine the advantages of COS, GNRs, FA, TGA, and DOX and have excellent biocompatibility, strong absorbance in the near-infrared (NIR) region, photostability, photothermal conversion efficiency, high targeting efficiency, fast drug release under laser irradiation, and tumor cell killing efficiency. FA–COS–TGA–GNRs–DOX exhibited significantly greater cell killing after laser irradiation. The intracellular uptake behavior of the targeted FA–COS–TGA–GNRs–DOX was confirmed by flow cytometry, two-photon fluorescence microscopy (TPFM), and confocal laser scanning microscopy (CLSM). More interestingly, the tumors in the presence of FA–COS–TGA–GNRs–DOX under laser irradiation were efficiently ablated and did not recur, showing an outstanding combined therapy of tumors. The combination of photothermal therapy (PTT) and photoacoustic imaging (PAI) could accurately locate and fully destroy tumor tissues after the intravenous injection of FA–COS–TGA–GNRs–DOX. Hence, this work offers a new avenue to develop a novel class of multifunctional nanomaterials as a drug delivery system for cancer therapy.

Photodynamic therapy (PDT) and photothermal therapy (PTT) using nanoparticles have gained significant attention for its therapeutic effect for cancer treatment. In the present study, we fabricated polypyrrole nanoparticles by employing bovine serum albumin-phycocyanin complex and the formulated particles were stable in various physiological solutions like water, phosphate buffered saline and culture media. The formulated nanoparticles did not cause any noticeable toxicity to MDA-MB-231 and HEK-293 cells. The obtained nanoparticles effectively killed MDA-MB-231 cells in a dual way upon laser illumination, one is through phycocyanin propagated reactive oxygen species (PDT) upon laser illumination and in another way it eradicated the treated cells by converting optical energy into heat energy (PTT). Additionally, the nanoparticles generated good amplitude of ultrasound signals under photoacoustic imaging (PAT) system that facilitates imaging of treated cells. In conclusion, the fabricated particles could be used as a multimodal therapeutic agent for treatment of cancer in the biomedical field.

In advanced cancer therapy, the combinational therapeutic effect of photothermal therapy (PTT) using near-infrared (NIR) light-responsive nanoparticles (NPs) and anti-cancer drug delivery-mediated chemotherapy has been widely applied. In the present study, using a facile, low-cost, and solution-based method, we developed and synthesized fucoidan, a natural polymer isolated from seaweed that has demonstrated anti-cancer effect, and coated NPs with it as an ideal candidate in chemo-photothermal therapy against cancer cells. Fucoidan-coated copper sulfide nanoparticles (F-CuS) act not only as a nanocarrier to enhance the intracellular delivery of fucoidan but also as a photothermal agent to effectively ablate different cancer cells (e.g., HeLa, A549, and K562), both in vitro and in vivo, with the induction of apoptosis under 808 nm diode laser irradiation. These results point to the potential usage of F-CuS in treating human cancer.

// Hyejin Kim 1, * , Van Phuc Nguyen 1, * , Panchanathan Manivasagan 2, * , Min Jung Jung 3 , Sung Won Kim 4 , Junghwan Oh 1, 2 and Hyun Wook Kang 1, 2 1 Interdisciplinary Program of Biomedical Mechanical and Electrical Engineering, Pukyong National University, Busan, South Korea 2 Department of Biomedical Engineering and Center for Marine-Integrated Biomedical Technology (BK 21 Plus), Pukyong National University, Busan, South Korea 3 Department of Pathology, Kosin University College of Medicine, Busan, South Korea 4 Department of Otolaryngology-Head and Neck Surgery, Kosin University College of Medicine, Busan, South Korea * These authors contributed equally to this work Correspondence to: Sung Won Kim, email: swforyou@gmail.com Junghwan Oh, email: jungoh@pknu.ac.kr Hyun Wook Kang, email: wkang@pukyong.ac.kr Keywords: doxorubicin; gold-nanoparticles; photothermal therapy; chemotherapy; eye tumor Received: October 16, 2017 Accepted: December 01, 2017 Published: December 09, 2017 ABSTRACT The current research demonstrates the feasible biomedical application of AuNPs coated with doxorubicin (Dox)-loaded fucoidan (Fu) for dual-chemotherapy and photothermal treatment (PTT) on eye tumors in vitro and in vivo . Marine-derived Fu was used as a capping agent to achieve high photostability for AuNPs, and Dox as a FDA-approved anti-cancer drug was added to induce chemotherapy. The synthesized Dox-Fu@AuNPs exhibited high cytotoxicity on the tumor cells and strong light absorption for temperature increase in vitro . After intratumoral injection of Dox-Fu@AuNPs in the rabbit eye tumors, PTT-assisted Dox-Fu@AuNPs entailed the complete removal of the eye tumors without recurrence for 14 days after the treatment. Photoacoustic image contrast from the tumor regions was enhanced due to selective light absorption by the administered Dox-Fu@AuNPs. Therefore, the proposed Dox-Fu@AuNPs can be a potential nano-theranostic material for treating and diagnosing the eye tumors.

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.

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 photot...

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 vitr...

Biofilm formed by several pathogenic bacteria results in the development of resistance against antimicrobial compounds. The polymeric materials present in the biofilm architecture hinder the entry of antimicrobial compounds through the surface of bacterial cells which are embedded as well as enclosed beneath the biofilm matrix. Recent and past studies explored the alternative approaches to inhibit the formation of biofilm by different agents isolated from plants, animals, and microbes. Among these agents, chitosan and its derivatives have got more attention due to their properties such as biodegradability, biocompatibility, non-allergenic and non-toxicity. Recent researches have focused on employing chitosan and its derivatives as effective agents to inhibit biofilm formation and attenuate virulence properties by various pathogenic bacteria. Such antibiofilm activity of chitosan and its derivatives can be further enhanced by conjugation with a wide range of bioactive compounds. The present review describes the antibiofilm properties of chitosan and its derivatives against the pathogenic bacteria. This review also summarizes the mechanisms of biofilm inhibition exhibited by these molecules. The knowledge of the antibiofilm activities of chitosan and its derivatives as well as their underlying mechanisms provides essential insights for widening their applications in the future.

The infection caused by Pseudomonas aeruginosa is a serious concern in human health. The bacterium is an opportunistic pathogen which has been reported to cause nosocomial and chronic infections through biofilm formation and synthesis of several toxins and virulence factors. Furthermore, the formation of biofilm by P. aeruginosa is known as one of the resistance mechanisms against conventional antibiotics. Natural compounds from marine resources have become one of the simple, cost-effective, biocompatible and non-toxicity for treating P. aeruginosa biofilm-related infections. Furthermore, hybrid formulation with nanomaterials such as nanoparticles becomes an effective alternative strategy to minimize the drug toxicity problem and cytotoxicity properties. For this reason, the present study has employed chitosan oligosaccharide for the synthesis of chitosan oligosaccharide-capped gold nanoparticles (COS-AuNPs). The synthesized COS-AuNPs were then characterized by using UV-Visible spectroscopy, Dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), Field emission transmission electron microscopy (FE-TEM), and Energy dispersive X-ray diffraction (EDX). The synthesized COS-AuNPs were applied for inhibiting P. aeruginosa biofilm formation. Results have shown that COS-AuNPs exhibited inhibition to biofilm as well as eradication to pre-existing mature biofilm. Simultaneously, COS-AuNPs were also able to reduce bacterial hemolysis and different virulence factors produced by P. aeruginosa. Overall, the present study concluded that the hybrid nanoformulation such as COS-AuNPs could act as a potential agent to exhibit inhibitory properties against the P. aeruginosa pathogenesis arisen from biofilm formation.

Developing new antibacterial nanomaterials and novel therapeutic strategies for the destruction of human pathogenic bacteria that cause infectious diseases is becoming more crucial, because infections caused by antibiotic-resistant bacteria are becoming more and more difficult to be effectively cured with commercially available antibiotics. In this study, we successfully developed new thiol chitosan-wrapped gold nanoshells (TC-AuNSs) as an antibacterial agent for the near-infrared (NIR) laser-triggered photothermal destruction of antibiotic-resistant pathogens, such as Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (Pseudomonas aeruginosa and Escherichia coli), owing to their high water solubility, biocompatibility, strong NIR absorption, and outstanding photothermal properties. More interestingly, TC-AuNSs (115 μg/mL) were capable of completely destroying S. aureus, P. aeruginosa, and E.coli within 5 min of NIR laser irradiation, and no bacterial growth was detected on the tryptic soy agar (TSA) plate after 48 h of laser irradiation, indicating that TC-AuNSs along with laser irradiation are highly efficient and can kill bacteria quickly and prevent bacterial regrowth. We believe that TC-AuNSs deserve much more attention as an antibacterial agent, to be used in effectively combating pathogenic bacteria associated with public health problems and monitoring of environmental pollution for hygiene and safety.

The emergence of antibiotic resistance in Pseudomonas aeruginosa due to biofilm formation has transformed this opportunistic pathogen into a life-threatening one. Biosynthesized nanoparticles are increasingly being recognized as an effective anti-biofilm strategy to counter P. aeruginosa biofilms. In the present study, gold nanoparticles (AuNPs) were biologically synthesized and stabilized using fucoidan, which is an active compound sourced from brown seaweed. Biosynthesized fucoidan-stabilized AuNPs (F-AuNPs) were subjected to characterization using UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), field emission transmission electron microscopy (FE-TEM), dynamic light scattering (DLS), and energy dispersive X-ray diffraction (EDX). The biosynthesized F-AuNPs were then evaluated for their inhibitory effects on P. aeruginosa bacterial growth, biofilm formation, virulence factor production, and bacterial motility. Overall, the activities of F-AuNPs towards P. aeruginosa were varied depending on their concentration. At minimum inhibitory concentration (MIC) (512 &micro, g/mL) and at concentrations above MIC, F-AuNPs exerted antibacterial activity. In contrast, the sub-inhibitory concentration (sub-MIC) levels of F-AuNPs inhibited biofilm formation without affecting bacterial growth, and eradicated matured biofilm. The minimum biofilm inhibition concentration (MBIC) and minimum biofilm eradication concentration (MBEC) were identified as 128 &micro, g/mL. Furthermore, sub-MICs of F-AuNPs also attenuated the production of several important virulence factors and impaired bacterial swarming, swimming, and twitching motilities. Findings from the present study provide important insights into the potential of F-AuNPs as an effective new drug for controlling P. aeruginosa-biofilm-related infections.

The fabrication of drug carriers, which are desirable for chemotherapy and thermal therapy, is considered to be an attractive approach to improving the efficacy of cancer therapy and to reducing the adverse side effects. In this study, we fabricated a crown ether triad (CET) unit modified core–shell magnetic mesoporous silica (FeNP@SiOH@CET) nanocarrier system for pH-responsive drug delivery and magnetic hyperthermia applications. The CET units were installed onto the FeNP@SiOH NPs through pH-responsive, metal–ligand complexation-based host–guest interactions. The surface modified CET gating units can effectively protect the encapsulated drugs (Dox) inside the mesopores of the FeNP@SiOH@CET NP system under physiological pH conditions and show a pH-responsive release performance under acidic pH environments in the presence of an alternating magnetic field (AMF). The MTT assay and intracellular uptake results evidenced that the synthesized FeNP@SiOH@CET NPs are biocompatible and can efficiently be taken up by MDA-MB-231 cells. Furthermore, the FeNP@SiOH@CET NPs exhibit superparamagnetic behavior with a magnetic saturation value of Ms = 60.2 emu g−1. In addition, the magnetic hyperthermia experiment supports that the FeNP@SiOH@CET NPs show fast and efficient temperature increases, and reach hyperthermia temperature (45 °C), within a short duration (∼4 min) in the presence of an applied magnetic field, which could be an appropriate temperature for local hyperthermia treatment in cancer therapy. Thus, the fabricated FeNP@SiOH@CET system can serve as a pH-responsive drug carrier as well as a hyperthermia agent. Owing to the synergistic effect of the FeNP@SiOH@CET NPs, they could be used for chemotherapy combined with magnetic hyperthermia-based thermal therapy applications in emerging cancer therapy.

The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) has recently gained much attention due to its selective and localized therapeutic effects by light irradiation. The reagents for phototherapy should have a large absorption coefficient in the near infrared region (NIR) (700 to 2500 nm) to maximize the depth of light penetration in tissues. In this study, we designed multifunctional nanoparticles that can provide strong NIR absorbing capability for the combined treatment of PTT and PDT. For the first time, FDA-approved photosensitizer methylene blue (MB) was conjugated with photothermal material polypyrrole (PPy) to form a novel NIR photo-absorber. The obtained PPy-MB NPs with an average size of 48.5 nm showed excellent biocompatibility, photothermal stability, and high NIR absorbance for the combined PTT and PDT. Under a NIR laser (e.g., 808 nm laser) at 0.5W cm(-2), the temperature of the aqueous solution containing 50 mg ml(-1) PPy-MB NPs reached up to 50 degrees C within a very short time and reactive oxygen species (ROS) were also generated. In vitro investigation confirmed the effectiveness of the PPy-MB NPs in killing the cancer cells under the NIR laser. Further, the phantom test of photoacoustic microscopy (PAM) used in conjunction with PPy-MB NPs showed a strong photoacoustic signal. Therefore, the novel PPy-MB NPs could be considered as promising single multifunctional nanoplatforms for further applications of photo-induced therapy and biomedical imaging.

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.

Photothermal therapy (PTT) using biocompatible nanomaterials have recently attracted much attention as a novel candidate technique for cancer therapy. In this work we report the performance of newly synthesized multidentate chitosan oligosaccharide modified gold nanorods (AuNRs-LA-COS) as novel agents for PTT of cancer cells due to their excellent biocompatibility, photothermal stability, and high absorption in the near-infrared (NIR) region. The AuNRs-LA-COS exhibit a strong NIR absorption peak at 838 nm with a mean length of 26 ± 3.1 nm and diameter of 6.8 ± 1.7 nm, respectively. The temperature of AuNRs-LA-COS rapidly reached 52.6 °C for 5 min of NIR laser irradiation at 2 W/cm2. The AuNRs-LA-COS had very low cytotoxicity and exhibited high efficiency for the ablation of breast cancer cells in vitro. The tumor-bearing mice were completely ablated without tumor recurrence after photothermal treatment with AuNRs-LA-COS (25 µg/mL) under laser irradiation. In summary, this study demonstrated that AuNRs-LA-COS with laser irradiation as novel agents pave an alternative way for breast cancer therapy and hold great promise for clinical trials in the near future.

Targeting cancer cells without injuring normal cells is the prime objective in treatment of cancer. In this present study, solvothermal and wet chemical precipitation techniques were employed to synthesize iron oxide (IO), hydroxyapatite (HAp), and hydroxyapatite coated iron oxide (IO-HAp) nanoparticles for magnetic hyperthermia mediated cancer therapy. The synthesized well dispersed spherical IO-HAp nanoparticles, magnetite, and apatite phases were confirmed by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR) and Field emission transmission electron microscopy (FETEM) with Energy Dispersive X-ray spectroscopy (EDS). The non-toxic behavior of synthesized IO-HAp nanoparticles was confirmed by cytotoxicity assay (Trypan blue and MTT assay). The synthesized nanoparticles revealed a remarkable magnetic saturation of 83.2 emu/g for IO and 40.6 emu/g for IO-HAp nanoparticles in presence of 15,000 Oe (1.5 T) magnetic field at room temperature (300 K). The magnetic hyperthermia study that was performed with IO-HAp nanoparticles showed an excellent hyperthermia effect (SAR value 85 W/g) over MG-63 osteosarcoma cells. The in vitro hyperthermia temperature (~45 °C) was reached within 3 min, which shows a very high efficiency and kills nearly all of the experimental MG-63 osteosarcoma cells within 30 min exposure. These results could potentially open new perceptions for biomaterials that are aimed for anti-cancer therapies based on magnetic hyperthermia.

Marine actinobacteria are one of the most efficient groups of secondary metabolite producers and are very important from an industrial point of view. Many representatives of the order Actinomycetales are prolific producers of thousands of biologically active secondary metabolites. Actinobacteria from terrestrial sources have been studied and screened since the 1950s, for many important antibiotics, anticancer, antitumor and immunosuppressive agents. However, frequent rediscovery of the same compounds from the terrestrial actinobacteria has made them less attractive for screening programs in the recent years. At the same time, actinobacteria isolated from the marine environment have currently received considerable attention due to the structural diversity and unique biological activities of their secondary metabolites. They are efficient producers of new secondary metabolites that show a range of biological activities including antibacterial, antifungal, anticancer, antitumor, cytotoxic, cytostatic, anti-inflammatory, anti-parasitic, anti-malaria, antiviral, antioxidant, anti-angiogenesis, etc. In this review, an evaluation is made on the current status of research on marine actinobacteria yielding pharmaceutically active secondary metabolites. Bioactive compounds from marine actinobacteria possess distinct chemical structures that may form the basis for synthesis of new drugs that could be used to combat resistant pathogens. With the increasing advancement in science and technology, there would be a greater demand for new bioactive compounds synthesized by actinobacteria from various marine sources in future.

The term "angiogenic switch" refers to a time-restricted event during tumor progression where the balance between pro- and anti-angiogenic factors, resulting in the transition from dormant avascularized hyperplasia to outgrowing vascularized tumor and eventually to malignant tumor progression. Targeting angiogenesis and its mechanistic pathways are critical target for cancer therapy. Recently, marine derived compounds, plays major role in cancer research. Several sponge derived compounds such as alkaloids, terpenes, macrocylic lactone and polyketide are leading drugs in the treatment of different types of diseases including cancer. Those marine sponge compounds inhibit cancer cell proliferation and tumor angiogenesis. Hence, this review sheds light on angiogenic regulators and marine sponge derived antiangiogenic compounds for 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.

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.

Marine actinobacteria are one of the most efficient groups of secondary metabolite producers and are very important from a pharmaceutical industry point of view. Among its various genera, Streptomyces, Saccharopolyspora , Amycolatopsis , Micromonospora , and Actinoplanes are the major producers of commercially important biomolecules. Several species have been isolated and screened from soil in the past decades. Consequently, the chance of isolating a novel actinobacteria strain from a terrestrial habitat, which would produce new biologically active metabolites, has been reduced. The most relevant reason for discovering novel secondary metabolites is to circumvent the problem of resistant pathogens, which are no longer susceptible to the currently used drugs. Existence of actinobacteria has been reported in the hitherto untapped marine ecosystem. Marine actinobacteria are efficient producers of new secondary metabolites that show a range of biological activities including antibacterial, antifungal, anticancer, antitumor, cytotoxic activities , etc. Bioactive compounds from marine actinobacteria possess distinct chemical structures that may form the basis for the synthesis of new drugs that could be used to combat resistant pathogens.

Nanotechnology is gaining tremendous attention in the present century due to its expected impact on many important areas such as medicine, energy, electronics, and space industries. In this context, actinobacterial biosynthesis of nanoparticles is a reliable, eco-friendly, and important aspect of green chemistry approach that interconnects microbial biotechnology and nanobiotechnology. Antibiotics produced by actinobacteria are popular in almost all the therapeutic measures and it is known that these microbes are also helpful in the biosynthesis of nanoparticles with good surface and size characteristics. In fact, actinobacteria are efficient producers of nanoparticles that show a range of biological properties, namely, antibacterial, antifungal, anticancer, anti-biofouling, anti-malarial, anti-parasitic, antioxidant, etc. This review describes the potential use of the actinobacteria as the novel sources for the biosynthesis of nanoparticles with improved biomedical applications.

Marine actinobacteria are emerging as a valuable resource for bioactive substances encompassing a variety of unique structural classes. Marine actinobacteria are one of the most efficient groups of secondary metabolite producers and are very important from an industrial point of view. Chemotherapy is one of the main treatments used to combat cancer. A great number of anticancer compounds are natural products or their derivatives, mainly produced by microorganisms. In particular, actinobacteria are efficient producers of a large number of bioactive natural products that show a range or biological activities including antimicrobial, anticancer and enzyme inhibition. Marine actinobacteria have attracted special attention in the last ten years for their ability to produce interesting pharmacological lead compounds.

Advancement of biological process for the synthesis of bionanoparticles is evolving into a key area of research in nanotechnology. The present study deals with the biosynthesis, characterization of gold bionanoparticles by Nocardiopsis sp. MBRC-48 and evaluation of their antimicrobial, antioxidant and cytotoxic activities. The gold bionanoparticles obtained were characterized by UV–visible spectroscopy, X-ray diffraction analysis, Fourier transform infrared spectroscopy, field emission scanning electron microscopy, energy dispersive X-ray analysis and transmission electron microscopy (TEM). The synthesized gold bionanoparticles were spherical in shape with an average of 11.57 ± 1.24 nm as determined by TEM and dynamic light scattering (DLS) particle size analyzer, respectively. The biosynthesized gold nanoparticles exhibited good antimicrobial activity against pathogenic microorganisms. It showed strong antioxidant activity as well as cytotoxicity against HeLa cervical cancer cell line. The present study demonstrated the potential use of the marine actinobacterial strain of Nocardiopsis sp. MBRC-48 as an important source for gold nanoparticles with improved biomedical applications including antimicrobial, antioxidant as well as cytotoxic agent.

Bone is a complex and hierarchical tissue consisting of nano hydroxyapatite and collagen as major portion. Several attempts have been made to prepare the artificial bone so as to replace the autograft and allograft treatment. Tissue engineering is a promising approach to solve the several issues and is also useful in the construction of artificial bone with materials including polymer, ceramics, metals, cells and growth factors. Composites consisting of polymer-ceramics, best mimic the natural functions of bone. Alginate, an anionic polymer owing enormous biomedical applications, is gaining importance particularly in bone tissue engineering due to its biocompatibility and gel forming properties. Several composites such as alginate-polymer (PLGA, PEG and chitosan), alginate-protein (collagen and gelatin), alginate-ceramic, alginate-bioglass, alginate-biosilica, alginate-bone morphogenetic protein-2 and RGD peptides composite have been investigated till date. These alginate composites show enhanced biochemical significance in terms of porosity, mechanical strength, cell adhesion, biocompatibility, cell proliferation, alkaline phosphatase increase, excellent mineralization and osteogenic differentiation. Hence, alginate based composite biomaterials will be promising for bone tissue regeneration. This review will provide a broad overview of alginate preparation and its applications towards bone tissue engineering.

Poultry waste is an abundant renewable source for the recovery of several value-added metabolites with potential industrial applications. This study describes the production of protease on poultry waste, with the subsequent use of the same poultry waste for the extraction of antioxidants. An extracellular protease-producing strain was isolated from Cuddalore coast, India, and identified asStreptomycessp. MAB18. Its protease was purified 17.13-fold with 21.62% yield with a specific activity of 2398.36 U/mg and the molecular weight was estimated as 43 kDa. The enzyme was optimally active at pH 8–10 and temperature 50–60°C and it was most stable up to pH 12 and 6–12% of NaCl concentration. The enzyme activity was reduced when treated with Hg2+, Pb2+, and SDS and stimulated by Fe2+, Mg2+, Triton X-100, DMSO (dimethyl sulfoxide), sodium sulphite, andβ-mercaptoethanol. Furthermore, the antioxidant activities of protease were evaluated usingin vitroantioxidant assays, such as DPPH radical-scavenging activity, O2scavenging activity, NO scavenging activity, Fe2+chelating activity, and reducing power. The enzyme showed important antioxidant potential with an IC50value of78±0.28 mg/mL. Results of the present study indicate that the poultry waste-derived protease may be useful as supplementary protein and antioxidant in the animal feed formulations.

Enterococcus faecium isolated from mangrove environment produced enterocin and it showed broad inhibitory spectrum against gram positive and gram negative bacteria such as Lactobacillus plantarum, Enterococcus facealis, Listeria monocytogens and Salmonella paratyphii. The optimum production of bacteriocin (2400 AU/ml) from E. faceium was obtained when the culture conditions were maintained at pH 6.0 and 35°C. Maximum yield was 40% in ion exchange chromatography. The molecular weight of the partially purified enterocin was estimated as 5 KDa by SDS PAGE electrophoresis.

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.