Surface Modification of Polymer Nanoparticles for Drug Delivery to Solid Tumors
For circulating nanoparticulate (NP) drug carriers to reach tumors, they need to avoid opsonization and subsequent elimination by the mononuclear phagocyte system. Various approaches have been developed to prevent protein absorption to NPs. For example, NPs are modified with hydrophilic and electrically neutral polymers such as polyethylene glycol (PEG) to delay the opsonization. However, the PEG layer also interferes with the interaction of NPs and cancer cells, resulting in poor cellular uptake and endosomal escape of NPs. For successful drug delivery with NPs, it is necessary to design an optimal surface chemistry that will protect the NPs from non-specific cellular uptake during circulation without compromising NP-cancer cell interactions. We developed albumin-coated NPs to resolve the conflicting needs for NP-cell interaction. We used a simple surface modification method based on dopamine polymerization (pD). The pD layer formed on NP surface provided reactive functional groups for albumin conjugation and allowed for reliable conjugation of albumin. NP-pD-Al (NPs coated with albumin via pD) had less albumin than NPxAl (NPs with albumin embedded on the surface), but it was superior to NPxAl in entering B16F10 cells across the confluent endothelial barrier in a co-culture system. Moreover, NP-pD-Al was taken up by J774A.1 macrophages much less than NPxAl and did not activate pro-inflammatory responses. Esterase activity assay and gel electrophoresis indicate that albumin conformation was better preserved in NP-pD-Al than NPxAl due to the mild preparation condition. These results indicate that the pD method helps to maintain the native conformation of albumin on the NP surface, which was critical to avoiding macrophage uptake and enhancing transendothelial transport and NP-cancer cell interactions. The mechanism by which albumin helps transport NPs and interaction with tumor cells are currently investigated. Potential pathways include transcytosis mediated by albumin-binding glycoprotein (gp60) expressed on endothelial cells and the interaction with secreted protein acidic and rich in cysteine (SPARC) overexpressed in tumor cells and interstitium.
Yeo, Purdue University.
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