The impact of PEGylation patterns on the in vivo biodistribution of mixed shell micelles

Hongjun Gao,^2# Jinjian Liu,^1# Cuihong Yang,¹ Tangjian Cheng,² Liping Chu,¹ Hongyan Xu,¹ Aimin Meng,¹ Saijun Fan,¹ Linqi Shi,² Jianfeng Liu<sup>1

1</sup>Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, People's Republic of China; ²Key Laboratory of Functional Polymer Materials, Ministry of Education, and Institute of Polymer Chemistry, Nankai University, Tianjin, People’s Republic of China

^#These two authors contributed equally in the present work

Abstract: Polyethylene glycol (PEG)-ylation is a widely used strategy to fabricate nanocarriers with a long blood circulation time. Further elaboration of the contribution of the surface PEGylation pattern to biodistribution is highly desirable. We fabricated a series of polyion complex (PIC) micelles PEGylated with different ratios (PEG2k and PEG550). The plasma protein adsorption, murine macrophage uptake, and in vivo biodistribution with iodine-125 as the tracer were systematically studied to elucidate the impact of PEGylation patterns on the biodistribution of micelles. We demonstrated that the PEGylated micelles with short hydrophilic PEG chains mixed on the surface were cleared quickly by the reticuloendothelial system (RES), and the single PEG2k PEGylated micelles could efficiently prolong the blood circulation time and increase their deposition in tumor sites. The present study extends the understanding of the PEGylation strategy to further advance the development of ideal nanocarriers for drug delivery and imaging applications.

Keywords: drug delivery, PEGylation, mixed shell micelles, macrophage uptake, in vivo biodistribution