Naghmeh Naderi

A new era of cancer treatment: carbon nanotubes as drug delivery tools

Cancer is a generic term that encompasses a group of diseases characterized by an uncontrolled proliferation of cells. There are over 200 different types of cancer, each of which gains its nomenclature according to the type of tissue the cell originates in. Many patients who succumb to cancer do not die as a result of the primary tumor, but because of the systemic effects of metastases on other regions away from the original site. One of the aims of cancer therapy is to prevent the metastatic process as early as possible. There are currently many therapies in clinical use, and recent advances in biotechnology lend credence to the potential of nanotechnology in the fight against cancer. Nanomaterials such as carbon nanotubes (CNTs), quantum dots, and dendrimers have unique properties that can be exploited for diagnostic purposes, thermal ablation, and drug delivery in cancer. CNTs are tubular materials with nanometer-sized diameters and axial symmetry, giving them unique properties that can be exploited in the diagnosis and treatment of cancer. In addition, CNTs have the potential to deliver drugs directly to targeted cells and tissues. Alongside the rapid advances in the development of nanotechnology-based materials, elucidating the toxicity of nanoparticles is also imperative. Hence, in this review, we seek to explore the biomedical applications of CNTs, with particular emphasis on their use as therapeutic platforms in oncology.

The efficacy of medicinal leeches in plastic and reconstructive surgery: A systematic review of 277 reported clinical cases

Background: Although there are numerous case reports and small case series describing the experiences of leech therapy in various circumstances, there are relatively few large studies evaluating the effectiveness of leeching to relieve venous congestion. The therapeutic value of leeching is illustrated by these reports but the current literature lacks a cohesive summary of previous experiences. Methods: An electronic search of PubMed, the Cochrane library and the Centre for Reviews and Dissemination between 1966 and 2009 was used to retrieve human studies published in the English language evaluating outcomes following leech therapy. The “success” and “failure” of leech therapy were the primary outcome measures and secondary outcomes included complications, number of leeches used, pharmacological adjuncts and blood transfusion requirements. Results: In total, out of 461 articles, 394 articles met the exclusion criteria. The 67 included papers reported on 277 cases of leech use with an age range of 2–81 years and a male to female ratio of almost 2:1. The overall reported “success” rate following leech therapy was 77.98% (216/277). In terms of secondary outcome measures, 49.75% of cases (N = 101) required blood transfusions, 79.05% received antibiotics (N = 166) and 54.29% received concomitant anticoagulant therapy. The overall complication rate was 21.8%. Conclusion: In the absence of robust randomized controlled trials on which the evidence may be based, this synthesis of current best evidence guides clinicians during the process of consenting patients and using leeches in their practice.

Medicinal leeches and the microsurgeon: A four‐year study, clinical series and risk benefit review

Background: There are case reports and small series in the literature relating to the use of medicinal leeches by plastic surgeons; however, larger series from individual units are rare. The aim of this article is to present a comprehensive 4‐year case series of the use of medicinal leeches, discuss the current evidence regarding indications, risks, and benefits and highlight the recent updates regarding leech speciation. Methods: Patients prescribed leeches in a 4‐year period (July 2004–2008) were collated from hospital pharmacy records (N = 35). The number of leeches used, demographic, clinical, and microbiological details were retrospectively analyzed. Results: Thirty‐five patients were treated with leeches. The age range was 2 to 98 years (mean = 49.3). Leeches were most commonly used for venous congestion in pedicled flaps and replantations. Blood transfusions were necessary in 12 cases (34%) [mean = 2.8 units, range 2–5 units]. Our infection rate was 20% (7/35) including five infections with Aeromonas spp. (14.2%). The proportion of patients becoming infected after leech therapy was significantly greater in the group of patients that did not receive prophylactic antibiotic treatment (Fishers Exact test P = 0.0005). In total, 14 cases (40%) were salvaged in entirety, in 7 cases 80% or more, in 2 cases 50 to 79%, and in 1 case less than 50% of the tissues were salvaged. In 11 cases (31%), the tissues were totally lost. Conclusion: Our study highlights both the benefits and the risks to patients in selected clinical situations and also the potential risks. The routine use of antibiotic prophylaxis is supported. In view of the emerging evidence that Hirudo verbana are now used as standard leech therapy, and the primary pathogen is Aeromonas veronii, until a large prospective multicenter study is published, large series of patients treated with leeches should be reported.

Adipogenic differentiation of adipose-derived stem cells in 3-dimensional spheroid cultures (microtissue): Implications for the reconstructive surgeon

BACKGROUND Adipose-derived stem cells (ADSC) can be readily extracted from adipose tissue, expanded in vitro, and have the capacity to differentiate into multiple cell lineages. This makes this cell type of great interest to the field of regenerative medicine. This study focuses on the isolation and characterisation of ADSC and their differentiation into adipocytes in a 3D microtissue model. METHODS Human ADSC were isolated from abdominal adipose tissue and characterised using multiparameter flow cytometry. ADSC were then expanded in culture and used to produce 3D scaffold-free micro-tissue. Adipogenic differentiation potential of micro-tissue constructs were subsequently characterised using Oil Red O staining. RESULTS Flow cytometric analysis showed ADSC were uniformly positive for CD34, CD73, CD90, and CD105, and negative for CD19, CD14, and CD45. The cells were functionally induced into adipocytes in the presence of appropriate conditioned media. CONCLUSION We have demonstrated that adipose-derived stem cells have the ability to form of microtissue and survive in vitro. We postulate that in the future this will result in an ADSC population which is injectable and can extend the delivery options of current stem cell-based therapies.

Adipose regeneration and implications for breast reconstruction: update and the future.

The evolution of breast reconstruction and management of breast cancer has evolved significantly since the earliest descriptions in the Edwin Smith Papyrus (3,000 BC). The development of surgical and scientific expertise has changed the way that women are managed, and plastic surgeons are now able to offer a wide range of reconstructive options to suit individual needs. Beyond the gold standard autologous flap based reconstructions, regenerative therapies promise the elimination of donor site morbidity whilst providing equivalent aesthetic and functional outcomes. Future research aims to address questions regarding ideal cell source, optimisation of scaffold composition and interaction of de novo adipose tissue in the microenvironment of breast cancer.

Carbon Nanotubes in the Diagnosis and Treatment of Malignant Melanoma

The potential role of carbon nanotubes (CNTs) in the diagnosis and treatment of malignant melanoma (MM) is still an emerging area of research. To date, there is strong evidence for the efficiency of CNTs in this therapeutic area, despite their unique physical, mechanical and biological properties. In this review, the application of CNTs in cancer diagnostics and treatment is reviewed, and consideration is given to the toxicity issues associated with their use.

Octa-ammonium POSS-conjugated single-walled carbon nanotubes as vehicles for targeted delivery of paclitaxel

Background Carbon nanotubes (CNTs) have unique physical and chemical properties. Furthermore, novel properties can be developed by attachment or encapsulation of functional groups. These unique properties facilitate the use of CNTs in drug delivery. We developed a new nanomedicine consisting of a nanocarrier, cell-targeting molecule, and chemotherapeutic drug and assessed its efficacy in vitro. Methods The efficacy of a single-walled carbon nanotubes (SWCNTs)-based nanoconjugate system is assessed in the targeted delivery of paclitaxel (PTX) to cancer cells. SWCNTs were oxidized and reacted with octa-ammonium polyhedral oligomeric silsesquioxanes (octa-ammonium POSS) to render them biocompatible and water dispersable. The functionalized SWCNTs were loaded with PTX, a chemotherapeutic agent toxic to cancer cells, and Tn218 antibodies for cancer cell targeting. The nanohybrid composites were characterized with transmission electron microscopy (TEM), Fourier transform infrared (FTIR), and ultraviolet–visible–near-infrared (UV–Vis–NIR). Additionally, their cytotoxic effects on Colon cancer cell (HT-29) and Breast cancer cell (MCF-7) lines were assessed in vitro. Results TEM, FTIR, and UV–Vis–NIR studies confirmed side-wall functionalization of SWCNT with COOH-groups, PTX, POSS, and antibodies. Increased cell death was observed with PTX–POSS–SWCNT, PTX–POSS–Ab–SWCNT, and free PTX compared to functionalized-SWCNT (f-SWCNT), POSS–SWCNT, and cell-only controls at 48 and 72 h time intervals in both cell lines. At all time intervals, there was no significant cell death in the POSS–SWCNT samples compared to cell-only controls. Conclusion The PTX-based nanocomposites were shown to be as cytotoxic as free PTX. This important finding indicates successful release of PTX from the nanocomposites and further reiterates the potential of SWCNTs to deliver drugs directly to targeted cells and tissues.

Evaluation of Sterilisation Techniques for Regenerative Medicine Scaffolds Fabricated with Polyurethane Nonbiodegradable and Bioabsorbable Nanocomposite Materials

An effective sterilisation technique that maintains structure integrity, mechanical properties, and biocompatibility is essential for the translation of new biomaterials to the clinical setting. We aimed to establish an effective sterilisation technique for a biodegradable (POSS-PCL) and nonbiodegradable (POSS-PCU) nanocomposite scaffold that maintains stem cell biocompatibility. Scaffolds were sterilised using 70% ethanol, ultraviolet radiation, bleach, antibiotic/antimycotic, ethylene oxide, gamma irradiation, argon plasma, or autoclaving. Samples were immersed in tryptone soya broth and thioglycollate medium and inspected for signs of microbial growth. Scaffold surface and mechanical and molecular weight properties were investigated. AlamarBlue viability assay of adipose derived stem cells (ADSC) seeded on scaffolds was performed to investigate metabolic activity. Confocal imaging of rhodamine phalloidin and DAPI stained ADSCs was performed to evaluate morphology. Ethylene oxide, gamma irradiation, argon plasma, autoclaving, 70% ethanol, and bleach were effective in sterilising the scaffolds. Autoclaving, gamma irradiation, and ethylene oxide led to a significant change in the molecular weight distribution of POSS-PCL and gamma irradiation and ethylene oxide to that of POSS-PCU (p<0.05). UV, ethanol, gamma irradiation, and ethylene oxide caused significant changes in the mechanical properties of POSS-PCL (p<0.05). Argon was associated with significantly higher surface wettability and ADSC metabolic activity (p<0.05). In this study, argon plasma was an effective sterilisation technique for both nonbiodegradable and biodegradable nanocomposite scaffolds. Argon plasma should be further investigated as a potential sterilisation technique for medical devices.