Biodegradable Mesoporous Organosilica Nanoparticle Drug Delivery Platform with Dual-targeting Protein affibody

Abstract

The usage of Protein Corona Shielded Nanoparticles (PCSN) as a nanocarrier is effective targeting way of the drug delivery system. It is attaching functionalized protein onto the Mesoporous silica nanoparticle (MSN) in advance, and functional protein inhibits protein adsoprtion which induces phagocytosis by macrophage. However, the investigation of controlled drug release profile of PCSN inside the cancer cell is still challenging for the perfection of the drug delivery. Because protein corona may inhibit the drug release from the nanoparticle. Although MSN could encapsulate high amount of hydrophobic drug, due to their property of staying inside interaction with nanoparticles may inhibit the drug release, it is needed to faciliate the drug release from inside of the nanoparticle. To give PCSN a function of the controlled release, the stimuli-responsive, and Biodegradable Mesoporous Organosilica Nanoparticles (MONs) could be better strategy in aspects of controlled release. MONs are consisted with silica containing disulfide bond, which response with higher GSH concetration of the tumor micro environment. The disulfide bond of MONs can be reduced by the GSH and degraded achieving better release than the conventional Mesoporous Silica Nanoparticles (MSNs). This degradation can occur higher amount of the delivery of the drug, leading to the effective cancer cell death than the MSNs. Not only enhancing the release profiles, it is expected to achieve universality of the protein modification, with various kinds of the protein-affibody. Dual modification can induce the enhanced effect of the targeting cancer cells, giving universality to the nanocarrier. Especially, it could target A431 cancer cell, which has both of the HER2, EGFR affibody receptor, showing more enhanced targeting ability than PCSN with a single affibody.