Aspect Ratio of PEGylated Upconversion Nanocrystals Affects the Cellular Uptake In Vitro and In Vivo

Fu，Libing1,2; Shi，Bingyang2; Wen，Shihui1; Morsch，Marco2; Wang，Guoying2; Zhou，Zhiguang1; Mi，Chao3; Sadraeian，Mohammad1; Lin，Gungun1; Lu，Yiqing4; Jin，Dayong1,3; Chung，Roger2

2022

10.1016/j.actbio.2022.05.029

Acta Biomaterialia   影响因子和分区

1742-7061

1878-7568

The central nervous system (CNS) is protected by the blood-brain barrier (BBB), which acts as a physical barrier to regulate and prevent the uptake of endogenous metabolites and xenobiotics. However, the BBB prevents most non-lipophilic drugs from reaching the CNS following systematic administration. Therefore, there is considerable interest in identifying drug carriers that can maintain the biostability of therapeutic molecules and target their transport across the BBB. In this regard, upconversion nanoparticles (UCNPs) have become popular as a nanoparticle-based solution to this problem, with the additional benefit that they display unique properties for in vivo visualization. The majority of studies to date have explored basic spherical UCNPs for drug delivery applications. However, the biophysical properties of UCNPs, cell uptake and BBB transport have not been thoroughly investigated. In this study, we described a one-pot seed-mediated approach to precisely control longitudinal growth to produce bright UCNPs with various aspect ratios. We have systematically evaluated the effects of the physical aspect ratios and PEGylation of UCNPs on cellular uptake in different cell lines and an in vivo zebrafish model. We found that PEGylated the original UCNPs can enhance their biostability and cell uptake capacity. We identify an optimal aspect ratio for UCNP uptake into several different types of cultured cells, finding that this is generally in the ratio of 2 (length/width). This data provides a crucial clue for further optimizing UCNPs as a drug carrier to deliver therapeutic agents into the CNS. Statement of Significance: The central nervous system (CNS) is protected by the blood-brain barrier (BBB), which acts as a highly selective semipermeable barrier of endothelial cells to regulate and prevent the uptake of toxins and pathogens. However, the BBB prevents most non-lipophilic drugs from reaching the CNS following systematic administration. The proposed research is significant because identifying the aspect ratio of drug carriers that maintains the biostability of therapeutic molecules and targets their transport across the blood-brain barrier (BBB) is crucial for designing an efficient drug delivery system. Therefore, this research provides a vital clue for further optimizing UCNPs as drug carriers to deliver therapeutic molecules into the brain.

aspect ratio blood-brain barrier cellular uptake PEG modification Upconversion nanorod

SCI ; EI

英语

其他

Australian Research Council Laureate Fellowship Program[FL210100180] ; National Health and Medical Research Council (NHMRC)["GNT1111611","GNT1166024"]

Engineering ; Materials Science

Engineering, Biomedical ; Materials Science, Biomaterials

WOS:000848054000022

ELSEVIER SCI LTD

20222212186025

Aspect ratio ; Biochemistry ; Blood ; Cell culture ; Controlled drug delivery ; Endothelial cells ; Metabolites ; Molecules ; Nanoparticles ; Neurophysiology ; Targeted drug delivery

Biological Materials and Tissue Engineering:461.2 ; Medicine and Pharmacology:461.6 ; Biology:461.9 ; Nanotechnology:761 ; Biochemistry:801.2 ; Atomic and Molecular Physics:931.3 ; Solid State Physics:933

2-s2.0-85131092242

Scopus

1.Institute for Biomedical Materials and Devices (IBMD),Faculty of Science,University of Technology Sydney,Sydney,2007,Australia
2.Department of Biomedical Sciences,Faculty of Medicine & Health Sciences,Macquarie University,Sydney,2109,Australia
3.UTS-SUStech Joint Research Centre for Biomedical Materials & Devices,Department of Biomedical Engineering,Southern University of Science and Technology,Shenzhen,China
4.Department of Physics and Astronomy,Macquarie University,Sydney,2109,Australia

Fu，Libing,Shi，Bingyang,Wen，Shihui,et al. Aspect Ratio of PEGylated Upconversion Nanocrystals Affects the Cellular Uptake In Vitro and In Vivo[J]. Acta Biomaterialia,2022,147:403-413.

Fu，Libing.,Shi，Bingyang.,Wen，Shihui.,Morsch，Marco.,Wang，Guoying.,...&Chung，Roger.(2022).Aspect Ratio of PEGylated Upconversion Nanocrystals Affects the Cellular Uptake In Vitro and In Vivo.Acta Biomaterialia,147,403-413.

Fu，Libing,et al."Aspect Ratio of PEGylated Upconversion Nanocrystals Affects the Cellular Uptake In Vitro and In Vivo".Acta Biomaterialia 147(2022):403-413.