Binding of HIV-1 gp120 glycoprotein to silica nanoparticles modified with CD4 glycoprotein and CD4 peptide fragments.

An important step in human immunodeficiency virus infection involves the interaction between the viral envelope glycoprotein gp120 and the human host cell surface receptor CD4. Herein, we describe a CD4-functionalized mesoporous silica-based system to selectively capture HIV-gp120 with high binding efficiency. Using a protection-deprotection strategy developed recently by our group, the external surface of the mesoporous particles was selectively functionalized with soluble CD4 ("sCD4") or an 18-peptide fragment mimicking the gp120 binding region. Confocal microscopy confirmed the CD4 locations and showed that the internal pores can be made accessible after external modification in a controlled manner. An evaluation of the ability of an 18-peptide CD4 fragment versus amide-immobilized sCD4 and sCD4 immobilized through its glycosidic group indicated that while all peptides were selective, the latter method was clearly best, with nearly complete removal of whole gp120 from solution. This study shows, for the first time, that sCD4 bound to mesoporous silica particles actively recognizes and retains high binding affinity for HIV-gp120. It is anticipated that, by proper modification of the accessible internal pores, our methodology can be adopted to develop porous platforms for HIV diagnosis, imaging, drug delivery, and vaccine development.