Top 10 developments in nanodermatology in 2013

(Nanowerk Spotlight) Nanotechnology has made great strides in biology and medicine in the past year. Here is a list of the top 10 developments in Nanodermatology in 2013, as compiled by the Nanodermatology Society:1. Chitosan nanoparticles for the treatment of Acne VulgarisAdvances in nanotechnology have demonstrated potential application of nanoparticles (NPs) for effective and targeted drug delivery. Here we investigated the antimicrobial and immunological properties and the feasibility of using NPs to deliver antimicrobial agents to treat a cutaneous pathogen. NPs synthesized with chitosan and alginate demonstrated a direct antimicrobial activity in vitro against Propionibacterium acnes, the bacterium linked to the pathogenesis of acne. Furthermore, benzoyl peroxide (BP), a commonly used antiacne drug, was effectively encapsulated in the chitosan–alginate NPs and demonstrated superior antimicrobial activity against P. acnes compared with BP alone while demonstrating less toxicity to eukaryotic cells. Together, these data suggest the potential utility of topical delivery of chitosan–alginate NP-encapsulated drug therapy for the treatment of dermatologic conditions with infectious and inflammatory components. (Read the paper in Journal of Investigative Dermatology: "Antimicrobial and Anti-Inflammatory Activity of Chitosan–Alginate Nanoparticles: A Targeted Therapy for Cutaneous Pathogens")2. Dendrimer embedded methotrexate for the treatment of squamous cell carcinomaImmunohistochemistry and an immunofluorescence technique was used to detect folate receptor expression in tissue samples and cell lines of head and neck squamous carcinoma, including 20 tissue samples of nasopharyngeal carcinoma, 16 tissue samples of laryngeal carcinoma, and HNE-1, HNE-2, CNE-1, CNE-2, SUNE-1, 5-8F, and Hep-2 cell lines. Head and neck squamous carcinoma cell strongly expressed the folate receptor, while normal tissue did not. The folate receptor can mediate endocytosis of folate-conjugated anticancer nanomedicines, and lays the foundation for molecular targeted treatment of cancer. (Read the paper in International Journal of Nanomedicine: "Expression of folate receptors in nasopharyngeal and laryngeal carcinoma and folate receptor-mediated endocytosis by molecular targeted nanomedicine ")3. Nanocantilevers for the detection of BRAF mutations in melanomaMalignant melanoma, the deadliest form of skin cancer, is characterized by a predominant mutation in the BRAF gene. Drugs that target tumours carrying this mutation have recently entered the clinic. Accordingly, patients are routinely screened for mutations in this gene to determine whether they can benefit from this type of treatment. The current gold standard for mutation screening uses real-time polymerase chain reaction and sequencing methods. Here we show that an assay based on microcantilever arrays can detect the mutation nanomechanically without amplification in total RNA samples isolated from melanoma cells. The assay is based on a BRAF-specific oligonucleotide probe. We detected mutant BRAF at a concentration of 500 pM in a 50-fold excess of the wild-type sequence. The method was able to distinguish melanoma cells carrying the mutation from wild-type cells using as little as 20 ng µl–1 of RNA material, without prior PCR amplification and use of labels. (Read the paper in Nature Nanotechnology: "Direct detection of a BRAF mutation in total RNA from melanoma cells using cantilever arrays")4. Topical vaccine delivery using microneedle patchesMeasles vaccination programs would benefit from delivery methods that decrease cost, simplify logistics, and increase safety. Conventional subcutaneous injection is limited by the need for skilled healthcare professionals to reconstitute and administer injections, and by the need for safe needle handling and disposal to reduce the risk of disease transmission through needle re-use and needlestick injury. Microneedles are micron-scale, solid needles coated with a dry formulation of vaccine that dissolves in the skin within minutes after patch application. By avoiding the use of hypodermic needles, vaccination using a microneedle patch could be carried out by minimally trained personnel with reduced risk of blood-borne disease transmission. The goal of this study was to evaluate measles vaccination using a microneedle patch to address some of the limitations of subcutaneous injection. These results show that measles vaccine can be stabilized on microneedles and that vaccine efficiently reconstitutes in vivo to generate a neutralizing antibody response equivalent to that generated by subcutaneous injection. (Read the paper in Vaccine: "Measles vaccination using a microneedle patch")5. Amphotericin B releasing nanoparticles for MDR candida burn infectionsCandida spp. infection in the context of burn wounds leads to invasive disease with a 14–70% mortality rate. Unfortunately, current administrations of AmB, an important therapeutic demonstrating minimal resistance, are only available via potentially cytotoxic IV infusions. In order to circumvent these sequelae, the researchers investigated the efficacy of nanoparticle encapsulated AmB (AmB-np) as a topical therapeutic against Candida spp. Their data support the concept that AmB-np can function as a topical antifungal in the setting of a burn wound. (Read the paper in Nanomedicine: "Amphotericin B releasing nanoparticle topical treatment of Candida spp. in the setting of a burn wound")6. Silica nanoparticle tissue adhesivesAdhesives are made of polymers because, unlike other materials, polymers ensure good contact between surfaces by covering asperities, and retard the fracture of adhesive joints by dissipating energy under stress. But using polymers to ‘glue’ together polymer gels is difficult, requiring chemical reactions, heating, pH changes, ultraviolet irradiation or an electric field. Here we show that strong, rapid adhesion between two hydrogels can be achieved at room temperature by spreading a droplet of a nanoparticle solution on one gel’s surface and then bringing the other gel into contact with it. The method relies on the nanoparticles’ ability to adsorb onto polymer gels and to act as connectors between polymer chains, and on the ability of polymer chains to reorganize and dissipate energy under stress when adsorbed onto nanoparticles. As a rapid, simple and efficient way to assemble gels or tissues, this method is desirable for many emerging technological and medical applications such as microfluidics, actuation, tissue engineering and surgery. (Read the paper in Nature: "Nanoparticle solutions as adhesives for gels and biological tissues")7. Flexible electronic tattoos for skin sensing and monitoringElectronic devices have advanced from their heavy, bulky origins to become smart, mobile appliances. Nevertheless, they remain rigid, which precludes their intimate integration into everyday life. Flexible, textile and stretchable electronics are emerging research areas and may yield mainstream technologies. Rollable and unbreakable backplanes with amorphous silicon field-effect transistors on steel substrates only 3 µm thick have been demonstrated. On polymer substrates, bending radii of 0.1 mm have been achieved in flexible electronic devices. Concurrently, the need for compliant electronics that can not only be flexed but also conform to three-dimensional shapes has emerged. Approaches include the transfer of ultrathin polyimide layers encapsulating silicon CMOS circuits onto pre-stretched elastomers, the use of conductive elastomers integrated with organic field-effect transistors (OFETs) on polyimide islands, and fabrication of OFETs and gold interconnects on elastic substrates to realize pressure, temperature and optical sensors. Here the researchers present a platform that makes electronics both virtually unbreakable and imperceptible. Applications include matrix-addressed tactile sensor foils for health care and monitoring, thin-film heaters, temperature and infrared sensors, displays, and organic solar cells (Read the paper in Nature: "An ultra-lightweight design for imperceptible plastic electronics")8. Nanovelcro for laser capture microdissection and diagnosis of melanomaA method to detect and isolate single circulating melanoma cells (CMCs) has been produced by integrating a polymer-nanofiber-embedded nanovelcro cell-affinity assay with a laser microdissection (LMD) technique. This method is able to separate CMCs from normal white blood cells (WBCs) and sequence individual cells for a specific mutation related to cancer progression, allowing for more personalized cancer therapy. (Read the paper in Angewandte Chemie International Edition: "Polymer Nanofiber-Embedded Microchips for Detection, Isolation, and Molecular Analysis of Single Circulating Melanoma Cells")9. Subcellular nanobiopsyThe ability to study the molecular biology of living single cells in heterogeneous cell populations is essential for next generation analysis of cellular circuitry and function. Here, we developed a single-cell nanobiopsy platform based on scanning ion conductance microscopy (SICM) for continuous sampling of intracellular content from individual cells. The nanobiopsy platform uses electrowetting within a nanopipette to extract cellular material from living cells with minimal disruption of the cellular milieu. The researchers demonstrate the subcellular resolution of the nanobiopsy platform by isolating small subpopulations of mitochondria from single living cells, and quantify mutant mitochondrial genomes in those single cells with high throughput sequencing technology. These findings may provide the foundation for dynamic subcellular genomic analysis. (Read the paper in ACS Nano: "Compartmental Genomics in Living Cells Revealed by Single-Cell Nanobiopsy")10. Carbon nanotube sensor for the diagnosis of melanomaDogs can identify, by olfaction, melanoma on the skin of patients or melanoma samples hidden on healthy subjects, suggesting that volatile organic compounds (VOCs) from melanoma differ from those of normal skin. Studies employing gas chromatography–mass spectrometry (GC–MS) and gas sensors reported that melanoma-related VOCs differed from VOCs from normal skin sources. However, the identities of the VOCs that discriminate melanoma from normal skin were either unknown or likely derived from exogenous sources. Here the researchers employed solid-phase micro-extraction, GC–MS and single-stranded DNA-coated nanotube (DNACNT) sensors to examine VOCs from melanoma and normal melanocytes. GC–MS revealed dozens of VOCs, but further analyses focused on compounds most likely of endogenous origin. Several compounds differed between cancer and normal cells, e.g., isoamyl alcohol was higher in melanoma cells than in normal melanocytes but isovaleric acid was lower in melanoma cells. These two compounds share the same precursor, viz., leucine. Melanoma cells produce dimethyldi- and trisulfide, compounds not detected in VOCs from normal melanocytes. Furthermore, analyses of the total volatile metabolome from both melanoma cells and normal melanocytes by DNACNT sensors, coupled with the GC–MS results, demonstrate clear differences between these cell systems. Consequently, monitoring of melanoma VOCs has potential as a useful screening methodology. (Read the paper in Journal of Chromatography B: "Volatile biomarkers from human melanoma cells")These topics will be the subject of multiple talks and two sessions at the American Academy of Dermatology Annual Meeting on March 21-25, 2014 in Denver.Firstly, Dr. Adam Friedman, Vice President of the Nanodermatology Society, Assistant Professor of Medicine and Physiology/Biophysics, and Director of Dermatologic Reserach at the Montefiore – Einstein College of Medicine will be presenting in Forum F013 on March 21st starting at 10:00 AM, room 708/710, on “The Role of Nanotechnology in the Delivery of Immunomodulatory and Biological Agents for Skin Disease.”This will then be followed that afternoon by a dedicated forum on nanotechnology from 1-3pm in same room at the Convention Center. Areas covered will include sunscreens, nanomaterials for wound healing, angiogenesis and nanodermatology, laser targeting of skin appendages, and skin barrier function.The skin’s barrier presents two pivotal challenges to nanotechnology. The first is overcoming the barrier to enhance penetration of useful nanomaterials. The second is targeting penetration of nanomaterials to specific epithelium. They are central to any discussion of the skin and advances in nanotechnology.Dr. Peter Elias, head of a multidisciplinary research group at UCSF, will focus on the structure, function and metabolic basis for the epidermal permeability barrier, mechanisms of normal epidermal differentiation, and the pathogenesis of ichthyosis. He is the winner of numerous awards including the William Montagna Award, is on the editorial board of many dermatology journals, the author of over 350 peer-reviewed articles; 50 chapters/books; and over 400 abstracts and has ongoing extramural funding from the NIH, the VA, as well as from industry.Dr. Jack Arbiser trained with Judah Folkman with an interest in angiogenesis and tumorigenesis. He has extended his work to study neovascularization in birthmarks, angiosarcoma, in benign neoplasms associated with tuberous sclerosis, and in malignant transformation of melanoma from a radial to a vertical growth phase. He will be discussing the role of nanotechnology in manipulating neoangiogenesis in these models.Dr. Rox Anderson is director of the Wellman Center for Photomedicine. He conceived and developed many of the non-scarring laser treatments now widely used in medical care. These include treatments for birthmarks, microvascular and pigmented lesions, tattoo and permanent hair removal. He has also contributed to treatment for vocal cords, kidney stones, glaucoma, heart disease, photodynamic therapy for cancer and acne, and optical diagnostics. He will be discussing the exploitation of surface plasmon resonance of gold nanoshells for targeted laser therapy of acne.Lastly, the Nanodermatology Society is hosting its fourth annual meeting at the Denver Sheraton in the Columbine Room on March 22, 5:30-7:30 pm. Topics include diagnosis of skin cancers including melanoma using carbon nanotube sensors to detect tumor emitted volatile organic compounds (VOCs), the development of effective vaccines for cutaneous delivery using nanoadjuvants, the pharmacoformulation of nanovehicles for targeted delivery of active ingredients to the skin and its appendages, and an overview of the skin penetration of nanomaterials.Among the speakers, Dr. Ross Kedl, who studied T cell and dendritic cell interaction in the laboratory of Drs. Philippa Marrack and John Kappler, has extensive immunology experience in academia and industry. He has been awarded numerous patents for the augmentation of innate immunity through Toll-like receptors and is developing nanoadjuvants for vaccines that have the potential for commercial use. He will discuss his research and bench-to-bedside applications of his work.Dr. Sarah Ibrahim is a pharmacologist with expertise in nanoformulation. She has years of academic and industry experience. She has been responsible for breakthroughs in transdermal, ocular and ungula drug delivery, iontophoresis, liposomes and nanoemulsions and has done this on a small scale in the laboratory and expanded this through industry experience in product/process development, formulation development, scale-up/technology transfer and process validation. She will be discussing the challenges and opportunities of nanoformulation for dermatology.Dr. Daniel Heller trained with Dr. Robert Langer at MIT and has worked extensively with carbon nanotubes. He has developed assays using nanotubes for real-time detection of troponin release in the setting of acute cardiac disease. Having validated the technology, he is expanding the use of carbon nanotube sensors for the detection of melanoma and for the assessment of tumor response to therapy in real time using minimal tissue.This is just a sampling of the topics to be covered and world class speakers in medical nanotechnology in Denver.

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