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Biomaterials. 2018 Oct;180:206-224. doi: 10.1016/j.biomaterials.2018.07.024. Epub 2018 Jul 18.

Surface modification of polymer nanoparticles with native albumin for enhancing drug delivery to solid tumors.

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Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN, 47907, USA.
School of Chemical Engineering, Purdue University, 480 West Stadium Avenue, West Lafayette, IN, 47907, USA.
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, South Korea.
Department of Comparative Pathobiology, Purdue University, West Lafayette, IN, 47907, USA.
Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN, 47907, USA; Weldon School of Biomedical Engineering, Purdue University, 206 South Martin Jischke Drive, West Lafayette, IN, 47907, USA. Electronic address:


Albumin is a promising surface modifier of nanoparticulate drug delivery systems. Serving as a dysopsonin, albumin can protect circulating nanoparticles (NPs) from the recognition and clearance by the mononuclear phagocytic system (MPS). Albumin may also help transport the NPs to solid tumors based on the increased consumption by cancer cells and interactions with the tumor microenvironment. Several studies have explored the benefits of surface-bound albumin to enhance NP delivery to tumors. However, it remains unknown how the surface modification process affects the conformation of albumin and the performance of the albumin-modified NPs. We use three different surface modification methods including two prevalent approaches (physisorption and interfacial embedding) and a new method based on dopamine polymerization to modify the surface of poly(lactic-co-glycolic acid) NPs with albumin and compare the extent of albumin binding, conformation of the surface-bound albumin, and biological performances of the albumin-coated NPs. We find that the dopamine polymerization method preserves the albumin structure, forming a surface layer that facilitates NP transport and drug delivery into tumors via the interaction with albumin-binding proteins. In contrast, the interfacial embedding method creates NPs with denatured albumin that offers no particular benefit to the interaction with cancer cells but rather promotes the MPS uptake via direct and indirect interactions with scavenger receptor A. This study demonstrates that the surface-bound albumin can bring distinct effects according to the way they interact with NP surface and thus needs to be controlled in order to achieve favorable therapeutic outcomes.


Albumin; Chemotherapy; Drug delivery; Nanoparticles; Surface modification

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