Tailored Dual PEGylation of Inorganic Porous Nanocarriers for Extremely Long Blood Circulation in Vivo

Drug carrier systems
based on mesoporous inorganic nanoparticles generally face the problem
of fast clearance from bloodstream thus failing in passive and active
targeting to cancer tissue. To address this problem, a specific dual
PEGylation (DPEG) method for mesoporous silicon (PSi) was developed
and studied in vitro and in vivo. The DPEG coating changed significantly
the behavior of the nanoparticles in vivo, increasing the circulation
half-life from 1 to 241 min. Furthermore, accumulation of the coated
particles was mainly taking place in the spleen whereas uncoated nanoparticles
were rapidly deposited in the liver. The protein coronas of the particles
differed considerably from each other. The uncoated particles had
substantially more proteins adsorbed including liver and immune active
proteins, whereas the coated particles had proteins capable of suppressing
cellular uptake. These reasons along with agglomeration observed in
blood circulation were concluded to cause the differences in the behavior
in vivo. The biofate of the particles was monitored with magnetic
resonance imaging by incorporating superparamagnetic iron oxide nanocrystals
inside the pores of the particles making dynamic imaging of the particles
feasible. The results of the present study pave the way for further
development of the porous inorganic delivery system in the sense of
active targeting as the carriers can be easily chemically modified
allowing also magnetically targeted delivery and diagnostics.