Thermo-sensitive amylase-starch double-layer polymer nanoparticles with self-polishing and protein corona-free property for drug delivery applications

Protein corona formation can lead to obstructive screening of targeting groups of nanoparticles (NPs). Also, the targeting groups are subjected to physiochemical interactions when exposed to solvents. Here, these two factors can influence NP targeting efficiency. Therefore, it is necessary to prepare a general method of preparing an anti-fouling NPs with protected targeting groups. Here, we designed α-amylase-starch double-layer coated poly (methyl methacrylate- co -acrylic acid) NPs (α-ams-SCMMA NPs), functionalized with aptamer targeting groups and doped with Tetrakis(para-hydraoxylphenyl) porphyrin (TPPOH) as a payload drug. Natural polysaccharide starch and enzyme α-amylase were applied here for thermo-sensitive activation of starch hydrolyzation in order to render the NPs' self-polishing from protein corona effects. During incubation with serum media, the protein corona was formed at the exterior shell of NPs, while the self-polishing process was activated to remove the “protein fouling” when the incubation temperature increased to 37 °C (body temperature). Mechanistically, the starch layer of α-ams-SCMMA NPs was readily hydrolysed by α-amylase, whereby the adsorbed protein corona could be efficiently eliminated and the targeting groups were then presented. With this unique self-polishing NP design, we believe our method can be applied for potential NP applications in cancer therepy due to excellent antifouling property and protected targeting groups.