Vascular Nanomedicine: Current Status, Opportunities, and Challenges

Abstract

The term “nanotechnology” was coined by Norio Taniguchi in the 1970s to describe the manipulation of materials at the nano (10−9) scale, and the term “nanomedicine” was put forward by Eric Drexler and Robert Freitas Jr. in the 1990s to signify the application of nanotechnology in medicine. Nanomedicine encompasses a variety of systems including nanoparticles, nanofibers, surface nano-patterning, nanoporous matrices, and nanoscale coatings. Of these, nanoparticle-based applications in drug formulations and delivery have emerged as the most utilized nanomedicine system. This review aims to present a comprehensive assessment of nanomedicine approaches in vascular diseases, emphasizing particle designs, therapeutic effects, and current state-of-the-art. The expected advantages of utilizing nanoparticles for drug delivery stem from the particle's ability to (1) protect the drug from plasma-induced deactivation; (2) optimize drug pharmacokinetics and biodistribution; (3) enhance drug delivery to the disease site via passive and active mechanisms; (4) modulate drug release mechanisms via diffusion, degradation, and other unique stimuli-triggered processes; and (5) biodegrade or get eliminated safely from the body. Several nanoparticle systems encapsulating a variety of payloads have shown these advantages in vascular drug delivery applications in preclinical evaluation. At the same time, new challenges have emerged regarding discrepancy between expected and actual fate of nanoparticles in vivo, manufacturing barriers of complex nanoparticle designs, and issues of toxicity and immune response, which have limited successful clinical translation of vascular nanomedicine systems. In this context, this review will discuss challenges and opportunities to advance the field of vascular nanomedicine.

Combination targeting of ‘platelets + fibrin’ enhances clot anchorage efficiency of nanoparticles for vascular drug delivery

“…Microparticle or nanoparticle targeting to platelets (via particle binding to single type of receptors or multiple types of receptors on platelet surface) has been extensively studied by our group and others, while nanoparticle targeting of fibrin has been studied by several research groups to achieve delivery of drugs or imaging agents to atherosclerotic and thrombotic disease sites. 28,34,[53][54][55][56][57] However, combination targeting of 'platelets + fibrin' to enhance clot-binding efficacy of nanoparticles has not been explored extensively. In fact, we found only one 'conference abstract' from almost 10 years ago that mention 'platelet and fibrin targeting' as a means to enhance ultrasound-responsive microbubble binding to thrombi for studying clot imaging and sonothrombolysis 58 , but it does not state any comparative analysis of platelet-targeting vs fibrin-targeting vs combination targeting in the context of imaging or thrombolytic efficacy.…”

“…[21][22][23][24][25][26][27] As a result, there continues to be significant clinical interest in strategies that can enable enhanced drug delivery specifically targeted to the clot site while minimizing systemic side effects. We and others have recently comprehensively reviewed such approaches 28,29 , where strategies for targeted drug delivery to clots have utilized either direct engineering of the drug to bear clotanchoring motifs or packaging of the drug within nanoparticles that are surface-decorated with clot-anchoring motifs. In either case, the strategies have majorly focused on anchoring to a singular entity, e.g.…”

Beyond the thrombus: Platelet‐inspired nanomedicine approaches in inflammation, immune response, and cancer

“…Significant research have been focused on elucidating these mechanisms, and developing therapeutics to modulate them for the treatment of hemorrhage by making clots (hemostatic therapy) and thrombosis by preventing or breaking clots (antithrombotic therapy) 7–9 . Nanomedicine, a field involving the design of nanoparticles with unique biointeractive surface modifications and payload encapsulation for disease‐targeted drug delivery, has become an important component of such therapeutic development 10–12 . Beyond their traditional role in forming good and bad clots, platelets have been implicated in several other pathologies, including innate and adaptive immune response against pathogens, inflammation, and cancer, via direct cellular interactions, as well as via secretion of soluble factors that aid in the disease microenvironment 13–21 .…”

Nanomedicine Research in India: A Bibliometric Assessment of Publications Output during 2002-20

“…They (nanomaterials) do play a very crucial role in drug development designed to enable benefits such as site specific drug delivery, safer imaging of diseased tissues, reduced side effects and better results compared to standard therapies. The term "nanomedicine" was coined by the American engineer Eric Drexler (1955) and Robert Freitas Jr. (1952) in the nineties, 1 with the publication of the multi-volume textbook entitled "Nanomedicine", released in October 1999. Nanomedicine technology uses structured nanomaterials in the treatment of diseases such as neurological diseases, infectious diseases, cardiology, oncology, orthopaedics, and others, not possible before.…”