Coupled benefits of nanotopography and titania surface chemistry in fostering endothelialization and reducing in-stent restenosis in coronary stents.

Recent advances in coronary stents have all been distinctively focused towards directing re-endothelialization with minimal in-stent restenosis, potentially via alterations in surface topographical cues, for augmenting the efficacy of vascular implants. This perspective was proven by our group utilizing a simple and easily scalable nanosurface modification strategy on metallic stents devoid of any drugs or polymers. In the present work, we explore the impact of surface characteristics in modulating this cell response in-vitro and in-vivo, using titania coated cobalt-chromium (CC) stents, with and without nanotopography, in comparison to commercial controls. Interestingly, titania nanotopography facilitated a preferential cell response in-vitro as against the titania coated and bare CC surfaces, which can be attributed to surface topography, hydrophilicity, and roughness. This in turn altered the cellular adhesion, proliferation and focal contact formations of endothelial and smooth muscle cells. We also demonstrate that titania nanotexturing plays a pivotal role in fostering rapid re-endothelialization with minimal neointimal hyperplasia, leading to excellent in-vivo patency of CC stents post 8 weeks implantation in rabbit iliac arteries, in comparison to bare CC, nano-less titania coated CC, and commercial drug-eluting stents (CC DES), without administering antiplatelet agents. This exciting result for the drug and polymer-free titania nanotextured stents, in the absence of platelet therapy, reveals the possibility of proposing an alternative to clinical DES for coronary stenting.

Surface engineering at the nanoscale: A way forward to improve coronary stent efficacy.

Coronary in-stent restenosis and late stent thrombosis are the two major inadequacies of vascular stents that limit its long-term efficacy. Although restenosis has been successfully inhibited through the use of the current clinical drug-eluting stent which releases antiproliferative drugs, problems of late-stent thrombosis remain a concern due to polymer hypersensitivity and delayed re-endothelialization. Thus, the field of coronary stenting demands devices having enhanced compatibility and effectiveness to endothelial cells. Nanotechnology allows for efficient modulation of surface roughness, chemistry, feature size, and drug/biologics loading, to attain the desired biological response. Hence, surface topographical modification at the nanoscale is a plausible strategy to improve stent performance by utilizing novel design schemes that incorporate nanofeatures via the use of nanostructures, particles, or fibers, with or without the use of drugs/biologics. The main intent of this review is to deliberate on the impact of nanotechnology approaches for stent design and development and the recent advancements in this field on vascular stent performance.

Successful Reduction of Neointimal Hyperplasia on Stainless Steel Coronary Stents by Titania Nanotexturing.

Bare metal stents (BMSs) of stainless steel (SS) were surface engineered to develop nanoscale titania topography using a combination of physical vapor deposition and thermochemical processing. The nanoleafy architecture formed on the stent surface remained stable and adherent upon repeated crimping and expansion, as well as under flow. This titania nanoengineered stent showed a preferential proliferation of endothelial cells over smooth muscle cells in vitro, which is an essential requirement for improving the in vivo endothelialization, with concurrent reduction of intimal hyperplasia. The efficacy of this surface-modified stent was assessed after implantation in rabbit iliac arteries for 8 weeks. Significant reduction in neointimal thickening and thereby in-stent restenosis with complete endothelial coverage was observed for the nanotextured stents, compared to BMSs, even without the use of any antiproliferative agents or polymers as in drug-eluting stents. Nanotexturing of stents did not induce any inflammatory response, akin to BMSs. This study thus indicates the effectiveness of a facile titania nanotopography on SS stents for coronary applications and the possibility of bringing this low-priced material back to clinics.

Stable Titania Nanostructures on Stainless Steel Coronary Stent Surface for Enhanced Corrosion Resistance and Endothelialization.

Stainless steel (SS) coronary stents continue to present risk of in-stent restenosis that impact its long term safety and efficacy. The present work focuses on developing a drug-free and polymer-less surface on coronary stents by utilizing a titania (TiO2 ) nanotexturing approach through hydrothermal processing, that will offer improved stent performance in vivo. Mechanically stable and durable nanotextured coatings are obtained on SS stents that also offer good corrosion resistance. In vitro vascular cell (endothelial and smooth muscle cells) studies on surface modified SS show preferential rapid endothelialization with enhanced nitric oxide production and reduce smooth muscle cell proliferation, in comparison to unmodified SS. In vivo evaluation of the nanotextured stents after subcutaneous implantation in rabbits show reduced irritability and minimal localized inflammatory response. These beneficial effects suggest that the stable, easily scalable titania nanosurface modification strategy on coronary stent surfaces can be a much cheaper alternative to drug eluting stents in addressing in-stent restenosis.

Effect of Baliospermum montanum nanomedicine apoptosis induction and anti-migration of prostate cancer cells.

Prostate cancer has been diagnosed as the second most frequent and the sixth among the cancer causing deaths among men worldwide. There is a limited scope for the prevalent therapies as prostate cancer advances and they present adverse aftermaths that have put way for us to delve into naturally available anticancer agents. The main objective of the present work is to compile the advantages of ayurvedic herbal formulations with modern technology. Baliospermum montanum is a plant that is used in ayurveda for the treatment of cancer and the plant is studied to possess various constituents in it that are responsible for its anticancer activity. Stable nanoparticles of B. montanum were prepared from both the aqueous and ethanolic extracts of the plant and its cytotoxic effects were studied on prostate cancer and normal cell lines. Size analysis by DLS and SEM revealed the average size of nanoparticles prepared was 100±50 nm and 150±50 nm for the nanoparticles prepared from aqueous and ethanolic extract respectively. In vitro cytotoxicity showed a concentration and time dependent toxicity on prostate cancer cells with cell viability of 22% and 6% with maximum concentration of aqueous and ethanolic nanoparticles respectively, in 48 h. In vitro hemolysis assay confirmed that the prepared nanoparticles were compatible with blood with no occurrence of hemolysis. The nanoparticles showed a significant reduction in the colony forming ability and wound healing capacity of the prostate cancer cells. These studies hold the anti cancer potential of the B. montanum nanoparticles making it an important candidate for prostate cancer therapy.

Nanotextured stainless steel for improved corrosion resistance and biological response in coronary stenting.

Nanosurface engineering of metallic substrates for improved cellular response is a persistent theme in biomaterials research. The need to improve the long term prognosis of commercially available stents has led us to adopt a 'polymer-free' approach which is cost effective and industrially scalable. In this study, 316L stainless steel substrates were surface modified by hydrothermal treatment in alkaline pH, with and without the addition of a chromium precursor, to generate a well adherent uniform nanotopography. The modified surfaces showed improved hemocompatibility and augmented endothelialization, while hindering the proliferation of smooth muscle cells. Moreover, they also exhibited superior material properties like corrosion resistance, surface integrity and reduced metal ion leaching. The combination of improved corrosion resistance and selective vascular cell viability provided by nanomodification can be successfully utilized to offer a cell-friendly solution to the inherent limitations pertinent to bare metallic stents.

Anti-diabetic drug metformin: challenges and perspectives for cancer therapy.

Metformin, a biguanide, is a commonly administered drug for the management of type 2 diabetes mellitus. The drug received tremendous recognition, when retrospective studies proved metformin-associated reduction in cancer risk. Metformin has potential anticancer effects and an ability to suppress tumor growth both in vitro and in vivo. Activation of LKB1/AMPK pathway and cancer stem cell destruction along with cell cycle arrest and apoptosis induction are the proposed mechanisms of anticancer potential of metformin. Nanotechnology approaches have also been adopted for metformin delivery to cancer cells. This review directs on the application of metformin for the therapy of various cancers and also the different pathways responsible for the metformin derived anticancer effect. It also focuses on the pharmacological applications of metformin and the nanotechnology approaches for metformin delivery.

The role of nanotechnology in prostate cancer theranostic applications.

Recent advancements in cancer nanotechnology have facilitated a better way to diagnosis and provide therapy for prostate cancer. Nanotechnology has the potential to battle tumors at the site, where the cancer begins. There is a need to improve the therapeutic availabilities and the effectiveness of conventional chemotherapeutic agents for prostate cancer. Many therapeutic NPs have been developed with nanotechnology that can specifically target and deliver variety of agents including chemo drugs to destruct the prostate cancer cells without causing any damage to the healthy cells. Theranostic NPs have been developed to specifically target the prostate cancer cells using targeting ligands and to release the anticancer agents in a controlled and time-dependent manner for cancer therapy in combination with assisted imaging to monitor the effectiveness of the therapy in real time. The natural products and surface-modified polymers and metallic NPs have evolved as promising nanomaterials for targeted prostate cancer treatment. This review focuses on the role of alternative medicine, polymeric and metallic and metal oxide NPs in prostate cancer theranostics.