Shape Effect of Glyco-Nanoparticles on Macrophage Cellular Uptake and Immune Response

Zhen Li; Liang Sun; Yufei Zhang; Andrew P Dove; Rachel K O'Reilly; Guosong Chen

doi:10.1021/acsmacrolett.6b00419

Shape Effect of Glyco-Nanoparticles on Macrophage Cellular Uptake and Immune Response

ACS Macro Lett. 2016 Sep 20;5(9):1059-1064. doi: 10.1021/acsmacrolett.6b00419. Epub 2016 Sep 11.

Authors

Zhen Li¹, Liang Sun², Yufei Zhang¹, Andrew P Dove², Rachel K O'Reilly², Guosong Chen¹

Affiliations

¹ The State Key Laboratory of Molecular Engineering of Polymers and Department of Macromolecular Science, Fudan University , Shanghai, 200433 China.
² Department of Chemistry, University of Warwick , Coventry CV4 7AL, United Kingdom.

Abstract

The shells of various poly(dl-lactide)-b-poly(acrylic acid) (PDLLA-b-PAA) spherical micelles and poly(l-lactide)-b-poly(acrylic acid) (PLLA-b-PAA) cylindrical micelles were functionalized with mannose to yield glyco-nanoparticles (GNPs) with different shapes and dimensions. All of these GNPs were shown to have good biocompatibility (up to 1 mg/mL). Cellular uptake experiments using RAW 264.7 have shown that the spherical GNPs were internalized to a much greater extent than the cylindrical GNPs and such a phenomenon was attributed to their different endocytosis pathways. It was demonstrated that spherical GNPs were internalized based on clathrin- and caveolin-mediated endocytosis while cylindrical GNPs mainly depended on clathrin-mediated endocytosis. We also found that longer cylindrical GNPs (L_n × W_n = 215 × 47 nm) can induce an inflammatory response (specifically interleukin 6) more efficiently than shorter cylindrical GNPs (L_n × W_n = 99 × 50 nm) and spherical GNPs (D_n = 46 nm).