MOLECULARLY IMPRINTED NANOGELS ACQUIRING STEALTH PROPERTY VIA REGULATING PROTEIN CORONA USING INTRINSIC SERUM ALBUMIN IN SITU

Nanomaterials prepared by nanotechnology are attracting significant attention as a new class of therapeutic agents. Recently, compositions of protein corona layers formed on the surface of nanomaterials after administration into blood vessels affect immune responses, and to achieve the efficient delivery of therapeutic agents towards target tissues, stealth properties to avoid the adsorption of opsonic proteins triggering the immune response is requisite for long blood circulation. The general strategy to obtain stealth property is to modify hydrophilic polymers such as polyethylene glycol on the nanomaterials to suppress non-specific adsorption of opsonic proteins. However, the strategy may not be suitable for the frequent administration due to the accelerated blood clearance phenomenon.

In this study, molecularly imprinted nanogels (MIP-NGs) that can acquire stealth capabilities in situ via regulating the protein corona composition by cloaking intrinsic dysopsonic proteins. Serum albumin was selected as a target dysopsonic protein, and MIP-NGs targeting serum albumin were prepared by precipitation polymerization in an aqueous buffered solution. The molecular recognition property of MIP-NGs was examined by surface plasmon resonance measurements with reference protein-immobilized sensor chips. A blood circulation test was conducted using in vivo confocal laser scanning microscopy. Tumour accumulation via enhanced permeability and retention (EPR) effect was confirmed with tumour-xenografted nude mice. Furthermore, MIP-NGs incorporated with gold nanoparticles (Au_MIP-NGs) were prepared, and by using Au_MIP-NGs, the distribution of MIP-NGs in mice was examined by quantitation of the accumulated gold nanoparticles in each organ. We believe that the strategy based on regulating the protein corona by molecular imprinting will develop novel therapeutic agents.