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Kharlamov A.N.,Erasmus Medical Center | Kharlamov A.N.,Ural Institute of Cardiology
Future Cardiology | Year: 2013

The advent of nanomedicine allowed for the development and design of tools that enhance detailed diagnosis and target treatment of atherosclerosis. Given the rapid progress in nanoagent synthesis and utility, clinical application of these technologies can be anticipated in the near future. This review article focuses on the development of these technologies in interventional cardiology, with the main goal of achieving atheroregression below a Glagov threshold of 40%. Special attention is given to plasmonic photothermal therapy. Vascular remodeling maintains the lumen dimension as long as the external elastic membrane can accommodate an increase in plaque burden that does not surpass a certain threshold. We propose that this threshold becomes the target for the development of strategies that reverse atherosclerosis, especially for the generation of devices and tools of nanomedicine. © 2013 Future Medicine Ltd. Source


Kharlamov A.N.,Erasmus Medical Center | Tyurnina A.E.,Ural Federal University | Veselova V.S.,Ural Institute of Cardiology | Novoselova O.S.,Ural Institute of Cardiology | And 4 more authors.
Journal of Nanomedicine and Nanotechnology | Year: 2013

Background: Atheroregression becomes an attractive target for cardiovascular treatment. Some clinical trials have demonstrated that intensive therapy with rosuvastatin or recombinant ApoA-I Milano can partially reduce the total atheroma volume (TAV) up to 6.38 mm3 or 14.1 mm3 respectively. Our previous bench studies of selected nanotechnologies documented TAV reduction up to unprecedented 79.4 mm3. Methods: The completed observational three arms (n=180) first-in-man trial (the NANOM FIM trial) assessed (NCT01270139) the safety and feasibility of two delivery techniques for nanoparticles (NP), and plasmonic photothermal therapy (PPTT). Patients were assigned to receive either (1) nano-intervention with delivery of silica-gold NP in bioengineered on-artery patch (n=60), or (2) nano-intervention with delivery of silica-gold iron-bearing NP with targeted micro-bubbles or stem cells using magnetic navigation system (n=60) versus (3) stent implantation (n=60). The primary outcome was TAV at 12 months. Results: The mean TAV reduction at 12 months in nano group was 60.3 mm3 (SD 39.5; min 41.9 mm3, max 94.2 mm3; p<0.05) up to mean 37.8% (95% CI: 31.1%, 51.7%; p<0.05) plaque burden. The analysis of the event free survival of the ongoing clinical follow-up shows the significantly lower risk of cardiovascular death in nano group when compared with others (91.7% vs 81.7% and 80% respectively; p<0.05) with no cases of the target lesion-related complications. Conslusions: PPTT using silica-gold NP associated with significant regression of coronary atherosclerosis. © 2013 Kharlamov AN, et al. Source


Kharlamov A.N.,Ural Institute of Cardiology | Gabinsky J.L.,Ural Institute of Cardiology
Rejuvenation Research | Year: 2012

Background: Some modern angioplasty techniques drastically affect the geometry of the plaque and the lumen, but have some inherent clinical and technical limitations. Methods: A total of 101 Yucatan miniature swine were allocated to the three following groups (34 pigs into 60/15- to 70/40-nm silica-gold nanoparticles (NPs), 34 swine into ferromagnetic group with iron-bearing NPs and delivery in hand of magnetic fields, and 33 in a sirolimus stenting control). Animals in the nanogroup were subdivided further into four subsets according to the delivery approach: (1) Intracoronary infused circulating stem progenitor cells (SPCs), including SP+ (side population) cells, (2) intracoronary infused, ultrasound-mediated, albumin-coated, gas-filled microbubbles, (3) CD73+105+ SPCs in the composition of a bioengineered on-artery patch (cardiac surgery), (4) CD73+CD105+ SPCs engrafted by manual subadventitial injection (cardiac surgery). NPs were detonated with a microwatt near-infrared (NIR) laser (821nm, 35-44 W/cm2 for 7min of exposure). Results: Changes of the total atheroma volume (TAV; mm3) immediately after the laser irradiation at month 6 in the nanoshell, ferromagnetic, and control groups were -7.54%/-22.92%, -9.7%/-16.84%, and -10.5%/-7.06% (p<0.01), respectively, and in the subsets reached -2.79%/-21.92%, -6.26%/-15.24%, -4.6%/-31.21%, -16.5%/-23.3% (p<0.05), respectively. Some cases of atherothrombosis and distal embolism (23.5%) were documented only in the microbubbles subset. The impact of the therapy on the nonorganic part of the plaque-antiinflammative and antiapoptotic effects, signs of neovascularization, and restoration of artery function-were predominant in the observed subsets with SPCs (p<0.01). Conclusion: Nanoburning, especially in combination with stem cell technologies, is a very challenging technique for altering advanced plaque and holds the promise of revolutionizing state-of-the-art interventional cardiology, assuring destruction of plaque and functional restoration of the vessel wall. It could potentially become the current mechanical and pharmacological treatment. © 2012 Mary Ann Liebert, Inc. Source


Kharlamov A.N.,Ural Institute of Cardiology | Gabinsky J.L.,Ural Institute of Cardiology
Technical Proceedings of the 2013 NSTI Nanotechnology Conference and Expo, NSTI-Nanotech 2013 | Year: 2013

Atheroregression becomes an attractive target for cardiovascular treatment. Some clinical trials have demonstrated that intensive therapy with rosuvastatin or recombinant ApoA-I Milano can partially reduce the total atheroma volume (TAV) up to 6.38 mm3 or 14.1 mm3 respectively. Our previous bench studies of selected nanotechnologies documented TAV reduction up to unprecedented 79.4 mm3. The completed observational three arms (n=180) first-in-man trial (the NANOM FIM trial) assessed (NCT01270139) the safety and feasibility of two delivery techniques for nanoparticles (NP), and plasmonic photothermal therapy (PPTT). Patients were assigned to receive either (1) nano-intervention with delivery of silica-gold NP in bioengineered on-artery patch (n=60), or (2) nano-intervention with delivery of silica-gold iron-bearing NP with targeted micro-bubbles or stem cells using magnetic navigation system (n=60) versus (3) stent implantation (n=60). The primary outcome was TAV at 12 months. The mean TAV reduction at 12 months in Nano group was 60.3 mm3 (SD 39.5; min 41.9 mm3, max 94.2 mm 3; p<0.05) up to mean 37.8% (95% CI: 31.1%, 51.7%; p< 0.05) plaque burden. The analysis of the event free survival of the ongoing clinical follow-up shows the significantly lower risk of cardiovascular death in Nano group when compared with others (91.7% vs 81.7% and 80% respectively; p<0.05) with no cases of the target lesion-related complications. So, PPTT using silica-gold NP associated with significant regression of coronary atherosclerosis. Source

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