Nanotechnology for angiogenesis: Opportunities and challenges

Angiogenesis plays a critical role within the human body, from the early stages of life (i.e., embryonic development) to life-threatening diseases (e.g., cancer, heart attack, stroke, wound healing). Many pharmaceutical companies have expended huge efforts on both stimulation and inhibition of angiogenesis. During the last decade, the nanotechnology revolution has made a great impact in medicine, and regulatory approvals are starting to be achieved for nanomedicines to treat a wide range of diseases. Angiogenesis therapies involve the inhibition of angiogenesis in oncology and ophthalmology, and stimulation of angiogenesis in wound healing and tissue engineering. This review aims to summarize nanotechnology-based strategies that have been explored in the broad area of angiogenesis. Lipid-based, carbon-based and polymeric nanoparticles, and a wide range of inorganic and metallic nanoparticles are covered in detail. Theranostic and imaging approaches can be facilitated by nanoparticles. Many preparations have been reported to have a bimodal effect where they stimulate angiogenesis at low dose and inhibit it at higher doses. This journal i

Water use of wheatbelt crop and pasture species

Water use of wheatbelt crop and pasture species Location: 83WH29 - Wongan Hills Research Station, Wongan Hills Abstract. A comprehensive experiment to investigate the productivity and water use of important wheatbelt crop and pasture species was undertaken in 1983. The experiment has provided important information on potential crop and pasture productivity and the role of alternate crop and pasture species in managing groundwater recharge and the development of secondary salinity. Contents 1. Background and industry significance 2. Aims of the experiment 3. Personnel 4. Site characterisation 5. Experimental detail 6. Results i) Meterological data ii) Dry matter, leaf area and grain yield iii) Soil Water iv) Root growth and water extraction v) Infra-red Thermometr

Biodistribution of charged 17.1A photoimmunoconjugates in a murine model of hepatic metastasis of colorectal cancer

Optimizing photodynamic therapy involves attempting to increase both the absolute tumour content of photosensitizer and the selectivity between tumour and surrounding normal tissue. One reason why photodynamic therapy has not been considered suitable for treatment of metastatic tumours in the liver, is the poor selectivity of conventional photosensitizers for tumour compared to normal liver. This report details an alternative approach to increasing this selectivity by the use of antibody-targeted photosensitizers (or photoimmunoconjugates) to target intrahepatic tumours caused by human colorectal cancer cells in the nude mouse, and explores the role of molecular charge on the tumour-targeting efficiency of macromolecules. The murine monoclonal antibody 17.1A (which recognizes an antigen expressed on HT 29 cells) was used to prepare site-specific photoimmunoconjugates with the photosensitizer chlorine6. The conjugates had either a predominant cationic or anionic charge and were injected i.v. into tumour-bearing mice. Biodistribution 3 or 24 h later was measured by extraction of tissue samples and quantitation of chlorine6 content by fluorescence spectroscopy. The photoimmunoconjugates were compared to the polylysine conjugates in an attempt to define the effect of molecular charge as well as antibody targeting. The anionic 17.1A conjugate delivered more than twice as much photosensitizer to the tumour at 3 h than other species (5 times more than the cationic 17.1A conjugate) and had a tumour:normal liver ratio of 2.5. Tumour-to-liver ratios were greater than one for most compounds at 3 h but declined at 24 h. Tumour-to-skin ratios were high (> 38) for all conjugates but not for free chlorine6. Cationic species had a high uptake in the lungs compared to anionic species. The photoimmunoconjugates show an advantage over literature reports of other photosensitizers, which can result in tumour:normal liver ratios of less than 1. © 2000 Cancer Research Campaign http://www.bjcancer.co

Photodynamic therapy plus regulatory T-cell depletion produces immunity against a mouse tumour that expresses a self-antigen

Background: Photodynamic therapy (PDT) can lead to development of antigen-specific immune response and PDT-mediated immunity can be potentiated by T regulatory cell (Treg) depletion. We investigated whether the combination of PDT with cyclophosphamide (CY) could foster immunity against wild-type tumours expressing self-antigen (gp70). Methods: Mice with CT26 tumours were treated with PDT alone or in combination with low-dose CY. T regulatory cell numbers and transforming growth factor-β (TGF-β) levels were measured at several time points after treatment. Mice cured by PDT+CY were rechallenged with CT26 and monitored for long-term survival. Results: Photodynamic therapy+CY led to complete tumour regression and long-term survival in 90% of treated mice while the absolute numbers of Treg decreased after PDT+CY and the TGF-β levels were reduced to a level comparable to naïve mice. Sixty-five percent of the mice treated with PDT+CY that survived over 90 days tumour free rejected the rechallenge with the same tumour when a second dose of CY was administered before rechallenge but not without. Conclusion: Administration of CY before PDT led to depletion of Treg and potentiated PDT-mediated immunity, leading to long-term survival and development of memory immunity that was only uncovered by second Treg depletion

Real-time evaluation of two light delivery systems for photodynamic disinfection of Candida albicans biofilm in curved root canals

Antimicrobial photodynamic therapy (APDT) combined with endodontic treatment has been recognized as an alternative approach to complement conventional root canal disinfection methods on bacterial biofilms. We developed an in vitro model of bioluminescent Candida albicans biofilm inside curved dental root canals and investigated the microbial reduction produced when different light delivery methods are employed. Each light delivery method was evaluated in respect to the light distribution provided inside curved root canals. After conventional endodontic preparation, teeth were sterilized before canals were contaminated by a bioluminescent strain of C. albicans (CEC789). Methylene blue (90 μM) was introduced into the canals and then irradiated (λ = 660 nm, P = 100 mW, beam diameter = 2 mm) with laser tip either in contact with pulp chamber or within the canal using an optical diffuser fiber. Light distribution was evaluated by CCD camera, and microbial reduction was monitored through bioluminescence imaging. Our findings demonstrated that the bioluminescent C. albicans biofilm model had good reproducibility and uniformity. Light distribution in dental tissue was markedly dependent on the light delivery system, and this strategy was directly related to microbial destruction. Both light delivery systems performed significant fungal inactivation. However, when irradiation was performed with optical diffuser fiber, microbial burden reduction was nearly 100 times more effective. Bioluminescence is an interesting real-time analysis to endodontic C. albicans biofilm inactivation. APDT showed to be an effective way to inactivate C. albicans biofilms. Diffuser fibers provided optimized light distribution inside curved root canals and significantly increased APDT efficiency.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, grant 2010/13313-9)Conselho Nacional de Pesquisas (Brazil) Conselho Nacional de Desenvolvimento Cientifico e TecnologicoNational Institute of Mental Health (U.S.) (NIH R01AI050875

"Photobiomics" : can light, including photobiomodulation, alter the microbiome?

Objective: The objective of this review is to consider the dual effects of microbiome and photobiomodulation (PBM) on human health and to suggest a relationship between these two as a novel mechanism. Background: PBM describes the use of low levels of visible or near-infrared (NIR) light to heal and stimulate tissue, and to relieve pain and inflammation. In recent years, PBM has been applied to the head as an investigative approach to treat diverse brain diseases such as stroke, traumatic brain injury (TBI), Alzheimer's and Parkinson's diseases, and psychiatric disorders. Also, in recent years, increasing attention has been paid to the total microbial population that colonizes the human body, chiefly in the gut and the mouth, called the microbiome. It is known that the composition and health of the gut microbiome affects many diseases related to metabolism, obesity, cardiovascular disorders, autoimmunity, and even brain disorders. Materials and methods: A literature search was conducted for published reports on the effect of light on the microbiome. Results: Recent work by our research group has demonstrated that PBM (red and NIR light) delivered to the abdomen in mice, can alter the gut microbiome in a potentially beneficial way. This has also now been demonstrated in human subjects. Conclusions: In consideration of the known effects of PBM on metabolomics, and the now demonstrated effects of PBM on the microbiome, as well as other effects of light on the microbiome, including modulating circadian rhythms, the present perspective introduces a new term "photobiomics" and looks forward to the application of PBM to influence the microbiome in humans. Some mechanisms by which this phenomenon might occur are considered

Mesenchymal stem cell-derived exosomes: A new therapeutic approach to osteoarthritis?

Degenerative disorders of joints, especially osteoarthritis (OA), result in persistent pain and disability and high costs to society. Nevertheless, the molecular mechanisms of OA have not yet been fully explained. OA is characterized by destruction of cartilage and loss of extracellular matrix (ECM). It is generally agreed that there is an association between pro-inflammatory cytokines and the development of OA. There is increased expression of matrix metalloproteinase (MMP) and "a disintegrin and metalloproteinase with thrombospondin motifs" (ADAMTS). Mesenchymal stem cells (MSCs) have been explored as a new treatment for OA during the last decade. It has been suggested that paracrine secretion of trophic factors, in which exosomes have a crucial role, contributes to the mechanism of MSC-based treatment of OA. The paracrine secretion of exosomes may play a role in the repair of joint tissue as well as MSC-based treatments for other disorders. Exosomes isolated from various stem cells may contribute to tissue regeneration in the heart, limbs, skin, and other tissues. Recent studies have indicated that exosomes (or similar particles) derived from MSCs may suppress OA development. Herein, for first time, we summarize the recent findings of studies on various exosomes derived from MSCs and their effectiveness in the treatment of OA. Moreover, we highlight the likely mechanisms of actions of exosomes in OA. © 2019 The Author(s)