Development of a click chemistry approach for cancer cell targeting and evaluating the effect of protein corona on active targeting yield

Nanoparticle;Targeted Drug Delivery;Click Chemistry;Protein Corona

Mirshafiee, Vahid ; Kraft ; Mary L.

关键词: Nanoparticle;    Targeted Drug Delivery;    Click Chemistry;    Protein Corona;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/44777/Vahid_Mirshafiee.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

The routine approach for targeting nanoparticle delivery vehicles to cancer cells is byincorporating targeting ligands (e.g. antibodies or aptamers) to the surface of nanoparticles(NPs). Although targeting ligands are known to interact with specific receptors in the membranesof cancer cells, resulting in enhanced NP uptake, these functionalized NPs have an undesirablebiodistribution and unfavorable targeting efficacy. Here we demonstrate a novel approach totarget NPs to the cancer cells via click chemistry. Cancer cells are first metabolically labeledwith an azide-modified monosaccharide (azidosugar). In the second step, NPs that arefunctionalized with highly-reactive cycloalkynes selectively bind to the cancer cells due to aspontaneous click reaction between the cycloalkynes on NP’s surfaces and the metabolicallyincorporated azide groups in the cell membranes. Our results show that HeLa and Chinesehamster ovary (CHO) cells are successfully labeled with azidosugars, and cycloalkyne-functionalizedsilica NPs bind to the metabolically labeled cells via the click reaction.The click chemistry reaction was also used to study the effect of protein adsorption on activeNP targeting. Upon exposure of NPs to the biological environment, proteins and otherbiomolecules bind to the NPs and cover their surfaces. This protein coating, which is called theprotein corona, may reduce the targeting capability of functionalized NPs by screening theirtargeting ligands. Here we used cycloalkyne-functionalized silica NPs that can bind to the azide-modified silicon substrates to study this effect. The results demonstrate that the formation ofprotein corona significantly decreased the conjugation of functionalized NPs to the substrate.