(10f) Exploiting Nano-Bio Interface to Overcome Circulatory Barriers and Augment Vascular Theranostics

One-dimensional (1D) nanoparticles and two-dimensional (2D) nanosheets have shown tremendous potential for a wide range of nanomedicine and theranostic applications, particularly for drug delivery, biomedical imaging, and disease diagnostics.^1,2 Nevertheless, due to the inability of these nanomaterials to overcome the numerous biological phenomena taking place in the circulatory system (i.e., circulatory barriers), such as biomolecule adsorption, blood flow shear stress, phagocytic clearance, and limited diffusion across vascular endothelium, the delivery and theranostic efficacies of nanomaterials remain poor.^3,4 Startlingly, the average delivery efficiency of nanomaterials toward target tissues over the past decade has been demonstrated to be less than 1%.⁴ Many attempts have been made to suppress circulatory barriers by modulating the behaviors of nanomaterials in physiological environments, which so far, has been primarily realized through manipulating nanomaterial properties. A large number of these efforts, however, fail to address the issue of circulatory barriers adequately due to a lack of fundamental understanding of the nanomaterial-barrier interactions. In addition, most studies have varied only one or two nanomaterial properties when examining the effect of nanomaterial design on barrier interactions. Critically, the interrelationship and interdependency of several physicochemical properties of nanomaterials in influencing their interactions with circulatory barriers remains unclear.

Here, I will present our research on the interactions between nanomaterials and circulatory barriers and how these findings can be translated into guiding principles for designing and formulating more effective theranostic nanoagents to overcome multiple circulatory barriers and combat vascular diseases. First, employing graphene oxide nanosheets as model 2D nanomaterials, I will describe our efforts in formulating biocompatible graphene oxide nanosheets resistant to non-specific biomolecule adsorption for preventing and minimizing thrombosis.^5-8 Second, using polymeric nanoparticles as model 1D nanomaterials, I will discuss our recent work in engineering nanoprobes for vascular imaging capable of avoiding immune surveillance and localizing preferentially at the vascular endothelium.⁹ These theranostic nanoagents were designed based on systematic investigations of the interactions between nanomaterials and biological entities responsible for circulatory barriers, such as plasma proteins, blood cells, macrophages, and endothelial cells. Importantly, the interdependent impacts of numerous nanomaterial properties, specifically size, size distribution, surface functionality, surface charge, and lipophilicity, on the elicited biological responses were comprehensively evaluated. Altogether, this talk will deepen our understanding on how the exploitation of nano-bio interface improves the rational engineering of theranostic nanoagents to conquer multiple biological barriers and combat vascular diseases. Moreover, the design framework originated from our studies can be readily translated into the formulation of nanoagents for diagnosing and treating other diseases.

References

1. Chen et al., Chemical Reviews 2016, 116, 2826-2885.
2. van der Meel et al., Nature Nanotechnology 2019, 14, 1007-1017.
3. Meng et al., Biomaterials 2018, 174, 41-53.
4. Wilhelm et al., Nature Reviews Materials 2016, 1, 16014.
5. Kenry et al., Small 2015, 11, 5105-5117.
6. Kenry et al., Nanoscale 2016, 8, 9425-9441.
7. Kenry et al., NPG Asia Materials 2017, 9, e422
8. Kenry et al., Nanoscale 2017, 9, 14065-14073.
9. Kenry et al., ACS Nano 2020, 14, 4509-4522.