Cuboidal tethered cyclodextrin frameworks tailored for hemostasis and injured vessel targeting

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.

Pulmonary Targeting Crosslinked Cyclodextrin Metal–Organic Frameworks for Lung Cancer Therapy

“…[34] Recently, we functionalized cubic crosslinked γ-CD-MOFs with GRGDS pentapeptides to construct efficient artificial platelets for bleeding control. [35] Our results proved that the unique cuboidal shape of CD-MOFs plays an important role in achieving hemostasis and in vivo targeting of artificial platelets. Porous γ-CD-MOFs were also utilized as templates to synthesize ultrafine silver nanoparticles (Ag NPs) by our group.…”

“…According to our previously reported strategy, the GRGDS pentapeptide was covalently adducted onto the CDF surface (RGD‐CDF) via an ester bond. [ 35 ]…”

“…According to our previously reported strategy, the GRGDS pentapeptide was covalently adducted onto the CDF surface (RGD-CDF) via an ester bond. [35] To prepare LMWH-modified CDF particles, cystamine (CYS) was selected as the redox-sensitive connecting arm. CYS reacted with the carbonyl groups of LMWH glycosaminoglycan units to synthesize LMWH-CYS amido adducts.…”

“…Biodistribution of CLD and RCLD Nanoparticles in Normal Tissues and Lung Tumors: The CLD and RCLD nanoparticles were first labeled with Cy5 fluorescent probes via ester linkage according to our previous report. [35] Briefly, 2.4 mg of Cyanine 5 NHS ester was dissolved in 5 mL of DMF, 230 mg of CLD or RCLD was added, and the reaction was stirred for 12 h at 37 °C in the dark. A metastatic lung cancer mouse model was used to study the biological distribution and lung cancer targeting of CLD and RCLD nanoparticles.…”

Effect on Platelet Function of Metal-Based Nanoparticles Developed for Medical Applications

“…Holzer et al have shown that carbon-based nanomaterials could induce thrombus formation in rodents independently of their shape (25). In contrast, He et al have recently demonstrated that cuboidal cyclodextrin frameworks enhanced platelet aggregation when compared with their spherical counterpart (26).…”