title: In vivo biodistribution of mixed shell micelles with tunable hydrophilic/hydrophobic surface.
abstract: The miserable targeting performance of nanocarriers for cancer therapy arises largely from the rapid clearance from blood circulation and the major accumulation in the organs of the reticuloendothelial system (RES), leading to inefficient enhanced permeability and retention (EPR) effect after intravenous injection (i.v.). Herein, we reported an efficient method to prolong the blood circulation of nanoparticles and decrease their deposition in liver and spleen. In this work, we fabricated a series of mixed shell micelles (MSMs) with approximately the same size, charge and core composition but with varied hydrophilic/hydrophobic ratios in the shell through spontaneously self-assembly of block copolymers poly(ethylene glycol)-block-poly(l-lysine) (PEG-b-PLys) and poly(N-isopropylacrylamide)-block-poly(aspartic acid) (PNIPAM-b-PAsp) in aqueous medium. The effect of the surface heterogeneity on the in vivo biodistribution was systematically investigated through in vivo tracking of the (125)I-labeled MSMs determined by Gamma counter. Compared with single PEGylated micelles, some MSMs were proved to be significantly efficient with more than 3 times lower accumulation in liver and spleen and about 6 times higher concentration in blood at 1 h after i.v.. The results provide us a novel strategy for future development of long-circulating nanocarriers for efficient cancer therapy.
authors.affiliation: Key Laboratory of Functional Polymer Materials, Ministry of Education, and Institute of Polymer Chemistry, Nankai University, Tianjin, China.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Gao
authors.forename: Jie
authors.initials: J
authors.lastname: Xiong
authors.forename: Tangjian
authors.initials: T
authors.lastname: Cheng
authors.forename: Jinjian
authors.initials: J
authors.lastname: Liu
authors.forename: Liping
authors.initials: L
authors.lastname: Chu
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Liu
authors.forename: Rujiang
authors.initials: R
authors.lastname: Ma
authors.forename: Linqi
authors.initials: L
authors.lastname: Shi
mesh_terms: D001692:Biological Transport; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers; D057927:Hydrophobic and Hydrophilic Interactions; D008099:Liver / Q000378:metabolism; D008823:Micelles; D012157:Mononuclear Phagocyte System / Q000378:metabolism; D053758:Nanoparticles; D009369:Neoplasms / Q000188:drug therapy; D011108:Polymers / Q000494:pharmacology*; D013154:Spleen / Q000378:metabolism; D013499:Surface Properties; D014018:Tissue Distribution / Q000187:drug effects*
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011108:Polymers