Theranostics 2019; 9(9):2489-2504. doi:10.7150/thno.31159

Research Paper

Cuboidal tethered cyclodextrin frameworks tailored for hemostasis and injured vessel targeting

Yaping He1,2, Jian Xu1,2, Xian Sun1,2, Xiaohong Ren1, Abi Maharjan1,2, Peter York3, Yong Su4✉, Haiyan Li1,2✉, Jiwen Zhang1,2✉

1. Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, China
2. University of Chinese Academy of Sciences, Beijing 100049, China
3. Institute of Pharmaceutical Innovation, University of Bradford, Bradford, West Yorkshire BD7 1DP, United Kingdom
4. Shanghai Fudan-zhangjiang Bio-Pharmaceutical Co., Ltd., Shanghai 201210, China

Abstract

Rationale: Targeted delivery of therapeutic drugs or imaging agents to injured blood vessels via nanocarriers is likely to be dependent on the particle shape, yet cubic nanoparticle carriers have not been reported for vascular targeting. Here, we demonstrate that cuboidal cyclodextrin frameworks possess superior hemostasis effect and injured vessels targeting compared with spherical counterpart.

Methods: Cuboidal and biocompatible γ-cyclodextrin metal-organic frameworks (CD-MOFs) are synthesized, tethered via crosslinking and surface modification with GRGDS peptide (GS5-MOFs). The specific interactions of cubic GS5-MOF nanoparticles with activated platelets were investigated by in vitro platelet aggregation assay and atomic force microscopy measurements (AFM). The hemostatic capacity and injured vessel targeting efficacy were evaluated in vivo.

Results: Cuboidal GS5-MOF nanoparticles exhibit enhanced adhesion and aggregation with activated platelets in vitro under static condition and a physiologically relevant flow environment. The cubic GS5-MOF nanoparticles show efficient hemostatic effects with bleeding time and blood loss decrease of 90% and strong injured vessel targeting in vivo, markedly superior to spherical γ-CD nanosponges with the same chemical composition.

Conclusions: These results clearly highlight the contribution of the cuboidal shape of GS5-MOFs to the enhanced aggregation of activated platelets and high targeting to damaged vessels. The cuboidal nanoparticle system provides an innovative delivery platform for the treatment and diagnosis of vascular diseases.

Keywords: cuboidal cyclodextrin frameworks, shape control, activated platelets, hemostasis, injured vessel targeting

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How to cite this article:
He Y, Xu J, Sun X, Ren X, Maharjan A, York P, Su Y, Li H, Zhang J. Cuboidal tethered cyclodextrin frameworks tailored for hemostasis and injured vessel targeting. Theranostics 2019; 9(9):2489-2504. doi:10.7150/thno.31159. Available from http://www.thno.org/v09p2489.htm