Design Considerations and Assays for Hemocompatibility of FDA-Approved Nanoparticles

Abstract

Nanoparticles have numerous biomedical applications including, but not limited to, targeted drug delivery, diagnostic imaging, sensors, and implants for a wide range of diseases including cancer, diabetes, heart disease, and tuberculosis. Although the mode of delivery of the nanoparticles depends on the application and the disease, the nanoparticles are often in immediate contact with the systemic circulation either because of intravenous administration or their ability to enter the bloodstream with relative ease or their longer survival time in circulation. Once in circulation, the nanoparticles may elicit unintended hemostatic and inflammatory responses, and hence the design of nanoparticles for therapeutic applications should take broad hemocompatibility concerns into consideration. In this review, we present the principles underlying the structural and functional design of various classes of nanoparticles that are currently approved by the US Food and Drug Administration, categorize these particles based on their interactions with cardiovascular tissues and ensuing adverse events, and also describe various in vitro assays that may be used evaluate their hemocompatibility.

Nanodiamond-Induced Thrombocytopenia in Mice Involve P-Selectin-Dependent Nlrp3 Inflammasome-Mediated Platelet Aggregation, Pyroptosis and Apoptosis

“…Analyses results revealed that among the various sizes (5-200 nm) of detonation NDs, with unknown reasons, treatments of 50 nm NDs induced highest level of platelet aggregation and thrombocytopenia, in vitro and in vivo . Complex factors may affect the hemocompatibility of nanomaterials in vivo , such as nanomaterial interaction and activation with respective types of blood cells and coagulation cascades ( 12 , 13 , 17 ). Thus, the mechanism of how 50 nm NDs displayed highest hemocompatibility-associated adverse effects is worthy of further investigated.…”

“…Despite of these in vitro studies, more recent studies have suggested ND is a promising and useful material for drug delivery and bio-labeling ( 5 , 9 – 11 ). Because of the potential biomedical applications of ND, and low hemocompatibility limits the use of nanoparticles ( 12 , 13 ), the hemocompatibility analyses become essential for NDs.…”

Virus-associated ribozymes and nano carriers against COVID-19

“…Despite these drawbacks associated with nanocarriers, there are currently approximately 35 commercial products based on non-viral vectors (nanoparticles) approved by FDA that have overcome the drawbacks [135].…”

A Multi-step In Vitro Hemocompatibility Testing Protocol Recapitulating the Foreign Body Reaction to Nanocarriers

“…However, through this route, the immunological response to the injected nanocarriers is increased significantly by their direct exposure to the circulating humoral and cellular elements key to the host response to a foreign body. Protein adsorption and cell contacts may activate pathways of the host response such as thrombogenicity and inflammation which may be due either to the direct recognition of the nano-biomaterials or as result of the unintended release of pro-inflammatory cytokines caused by cytotoxicity and consequent loss of cell integrity [8].…”

“…The regulatory approval of novel nanocarriers depends on the successful demonstration of their biocompatibility through a sequence of in vitro and in vivo tests [8]. In vitro tests are particularly important to optimise nanocarriers as they enable scientists in both academia and industry to screen a wide range of formulations before progressing the best candidates to the pre-clinical animal models.…”