Plasmonic Photothermal Therapy of Atherosclerosis With Nanoparticles: long-term Outcomes and Safety in NANOM-FIM Trial

Abstract

Aim: The safety options in nanomedicine raise an issue of the optimal niche at the real-world clinical practice. Methods: This is an observational prospective cohort analysis of the 5-year clinical outcomes at the intention-to-treat population (nano vs ferro vs stenting; n = 180) of NANOM first-in-man trial (NCT01270139). Results: Mortality (6 vs 9 vs 10 cases of cardiac death in groups, p < 0.05), major adverse cardiovascular events (14.3 vs 20.9 vs 22.9%, p = 0.04), late thrombosis (2 vs 4 vs 6, p < 0.05) and target lesion revascularization (3.8 vs 4.8 vs 5.7%, p = 0.04) were significantly higher in ferro group and stent control at 60 months. Conclusion: NANOM first-in-man trial demonstrates high safety with better rate of mortality, major adverse cardiovascular events and target lesion revascularization at the long-term follow-up if compare with stent XIENCE V.

KEYWORDS :

• long-term outcomes
• nanomedicine
• regression of atherosclerosis
• safety
• silica-gold nanoparticles

Acknowledgements

The authors appreciate the research assistance and nonprofit service of the members of NANOM-FIM trial consortium who are employees of the Ural Institute of Cardiology (UIC, Yekaterinburg, Russia), Ural Medical University (UMU, Yekaterinburg, Russia), Ural Center for Modern Nanotechnologies of the Ural Federal University (UCMN, Yekaterinburg, Russia) and independent CoreLab of the Heart Clinic (Yekaterinburg, Russia) for the outpatient supervision, the imaging and clinical lab expert analysis as well as tremendous intellectual contribution, particularly JL Gabinsky, (UIC, UMU), MS Freydlin (UIC), OP Kovtun (UMU) and IV Zubarev (UCMN). AN Kharlamov thanks FP7-IIF Marie-Curie Individual Fellowship program of the European Commission in 2011–2013 for support of the DREAM (Development of Bioresorbable Scaffolds and Nanotechnologies for Reversal of Atherosclerosis (grant no. 329728 by the program FP7-PEOPLE-2012-IIF) project under mentorship of PW Serruys (Erasmus MC, Rotterdam, the Netherlands, Imperial College, London, UK).

Author contributions

AN Kharlamov (ORCiD 0000-0003-4631-1261) has contributed to all the stages of the research project NANOM-FIM from preparations and project management to the lab work, analysis, management of patients, statistical processing and paper writing. JA Feinstein, JA Cramer and JA Boothroyd have contributed to few stages of the research project NANOM-FIM, particularly to the lab work, analysis and management of patients. EV Shishkina (a senior investigator) and V Shur (director of the Center of Modern Nanotechnologies of the Ural Federal University, Yekaterinburg, Russia; ORCiD 0000-0002-6970-7798) has contributed to the executive management of the project without involvement to the main research part of the project. All authors reviewed the manuscript. The corresponding author ensured that all authors were included in the author list, its order has been agreed by all authors, and that all authors were aware that the paper was submitted.

Financial & competing interests disclosure

AN Kharlamov (ORCiD 0000-0003-4631-1261) has nothing to financially disclose. JA Feinstein, JA Cramer, JA Boothroyd, EV Shishkina and V Shur have nothing to financially disclose. The authors have no any competing financial interests. Coauthors JA Feinstein, JA Cramer and JA Boothroyd have a special agreement/confidentiality disclosure with Ural Institute of Cardiology (Yekaterinburg, Russia) without financial interest. There is no direct research support granted from any parties, or financial gain related to the authors’ employment without personal financial interest. There is an agreement between Russian and Dutch parties with a transfer of all the intellectual rights to the benefit of De Haar Research Foundation (Rotterdam, The Netherlands, NY, NY, USA) by the DREAM project funded by the European Commission. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.