title: Online open-tubular fractionation scheme coupled with push-pull perfusion sampling for profiling extravasation of gold nanoparticles in a mouse tumor model.
abstract: The extravasation of administered nano-drug carriers is a critical process for determining their distributions in target and non-target organs, as well as their pharmaceutical efficacies and side effects. To evaluate the extravasation behavior of gold nanoparticles (AuNPs), currently the most popular drug delivery system, in a mouse tumor model, in this study we employed push-pull perfusion (PPP) as a means of continuously sampling tumor extracellular AuNPs. To facilitate quantification of the extravasated AuNPs through inductively coupled plasma mass spectrometry, we also developed a novel online open-tubular fractionation scheme to allow interference-free determination of the sampled extracellular AuNPs from the coexisting biological matrix. After optimizing the flow-through volume and flow rate of this proposed fractionation scheme, we found that (i) the system's temporal resolution was 7.5h(-1), (ii) the stability presented by the coefficient of variation was less than 10% (6-h continuous measurement), and (iii) the detection limits for the administered AuNPs were in the range 0.057-0.068μgL(-1). Following an intravenous dosage of AuNPs (0.3mgkg(-1) body weight), in vivo acquired profiles indicated that the pegylated AuNPs (PEG-AuNPs) had greater tendency toward extravasating into the tumor extracellular space. We also observed that the accumulation of nanoparticles in the whole tumor tissues was higher for PEG-AuNPs than for non-pegylated ones. Overall, pegylation appears to promote the extravasation and accumulation of AuNPs for nano-drug delivery applications.
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing-Hua University, 30013 Hsinchu, Taiwan.
authors.forename: Cheng-Kuan
authors.initials: CK
authors.lastname: Su
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing-Hua University, 30013 Hsinchu, Taiwan.
authors.forename: Po-Jen
authors.initials: PJ
authors.lastname: Tseng
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing-Hua University, 30013 Hsinchu, Taiwan.
authors.forename: Meng-Han
authors.initials: MH
authors.lastname: Lin
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing-Hua University, 30013 Hsinchu, Taiwan.
authors.forename: Hsien-Ting
authors.initials: HT
authors.lastname: Chiu
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing-Hua University, 30013 Hsinchu, Taiwan.
authors.forename: Andrea
authors.initials: A
authors.lastname: del Vall
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing-Hua University, 30013 Hsinchu, Taiwan.
authors.forename: Yu-Fen
authors.initials: YF
authors.lastname: Huang
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing-Hua University, 30013 Hsinchu, Taiwan. Electronic address: ycsun@mx.nthu.edu.tw.
authors.forename: Yuh-Chang
authors.initials: YC
authors.lastname: Sun
mesh_terms: D000818:Animals; D005591:Chemical Fractionation; D004195:Disease Models, Animal; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000592:standards; D005110:Extracellular Space / Q000737:chemistry; D006046:Gold / Q000032:analysis*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000032:analysis*; D009369:Neoplasms / Q000737:chemistry* / Q000378:metabolism
chemical_list: D004337:Drug Carriers; D006046:Gold
keywords: Extravasation; Fractionation; Gold nanoparticle; Push–pull perfusion; Tumor extracellular fluid