Exploring the Effect of Drug Loading on the Biological Fate of Polymer-Coated Solid Nanoparticles

Polymer-coated inorganic nanoparticles (NPs) have attractedgreatattention in drug delivery fields due to their unique magnetic, optical,and thermal properties. Recent studies have shown that the surfacephysicochemical properties of these NPs, including the size, shape,shell hydration, protein corona, and so forth, affect their biologicalfate. However, there has been less attention on the effect of thedrug loading amount on the biological activity of inorganic NPs. Here,we used upconverting NPs (UCNPs) as an inorganic nanocarrier model,coated them with a triblock terpolymer poly-(poly-(ethylene glycol)methyl ether methacrylate)-block-polymethacrylicacid-block-ethylene glycol methacrylate phosphate(PPEGMEMA-b-PMAA-b-PEGMP), and loadedthem with different amounts of anticancer drug doxorubicin (DOX) byelectrostatic interactions. Our results show that the UCNPs with thelowest DOX loading amount (1.32%) have the best biological behavior.We find that the effect of DOX loading on the biological behaviorof UCNPs is dominated by polymer shell hydration and the protein corona.The lowest drug-loading UCNPs are more hydrated and have more albumincoronas around, which leads to an increasing effect on the associationwith cancer cells and drug accumulation in the mouse tumor area. Ourfindings highlight the importance of optimizing the drug loading amountsin polymer-coated inorganic drug delivery systems as the amount andtype of drug will alter the physical properties of the polymer shell.