Tailored Surface Functionalization of Porous Silicon Nanoparticles for Efficient Intracellular Delivery

Protein corona formation and opsonization of nanoparticles is one of the major concerns that disturb the targeting receptor recognition. Coating the surface of nanoparticles with polyethylene glycol (PEG) is widely demonstrated as an anti-opsonization strategy to reduce such protein corona formation for improving specific delivery to targeted cells. However, excessive surface passivation with PEG can lead to strong inhibition of cellular uptake and less efficient binding to target receptors, resulting in reduced potential of targeted delivery. To improve the specific cell targeting while reducing the protein corona formation, the secondary packaging of the nanoparticles with shorter PEG chains, making the targeting ligands densely stretched out. In particular, we present the tailored surface functionalization of the porous nanoparticles that require the stealth shealing onto the open-pore region. Since the distance between neighboring PEG chains determines the structural conformation of the grafted PEG molecules, well-controlled PEG combination can efficiently resist the adsorption of serum proteins onto the pores. The balanced PEG conformation with secondary packaging of shorter PEG chains could be a promising anti-opsonization and active targeting strategy for efficient intracellular delivery of the nanoparticles.