title: Interactions of Renal-Clearable Gold Nanoparticles with Tumor Microenvironments: Vasculature and Acidity Effects.
abstract: The success of nanomedicines in the clinic depends on our comprehensive understanding of nano-bio interactions in tumor microenvironments, which are characterized by dense leaky microvasculature and acidic extracellular pH (pHe) values. Herein, we investigated the accumulation of ultrasmall renal-clearable gold NPs (AuNPs) with and without acidity targeting in xenograft mouse models of two prostate cancer types, PC-3 and LNCaP, with distinct microenvironments. Our results show that both sets of AuNPs could easily penetrate into the tumors but their uptake and retention were mainly dictated by the tumor microvasculature and the enhanced permeability and retention effect over the entire targeting process. On the other hand, increased tumor acidity indeed enhanced the uptake of AuNPs with acidity targeting, but only for a limited period of time. By making use of simple surface chemistry, these two effects can be synchronized in time for high tumor targeting, opening new possibilities to further improve the targeting efficiencies of nanomedicines.
authors.affiliation: Department of Chemistry and Biochemistry, The University of Texas at Dallas, 800 W. Campbell Rd., Richardson, TX, 75080, USA.
authors.forename: Mengxiao
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Chemistry and Biochemistry, The University of Texas at Dallas, 800 W. Campbell Rd., Richardson, TX, 75080, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Radiology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX, 75390, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Shanrong
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Chemistry and Biochemistry, The University of Texas at Dallas, 800 W. Campbell Rd., Richardson, TX, 75080, USA.
authors.forename: Shasha
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Chemistry and Biochemistry, The University of Texas at Dallas, 800 W. Campbell Rd., Richardson, TX, 75080, USA.
authors.forename: Julia D
authors.initials: JD
authors.lastname: Hankins
authors.affiliation: Department of Radiology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX, 75390, USA.
authors.forename: Xiankai
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Chemistry and Biochemistry, The University of Texas at Dallas, 800 W. Campbell Rd., Richardson, TX, 75080, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000818:Animals; D006046:Gold / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D050997:Nanomedicine; D009374:Neoplasms, Experimental / Q000737:chemistry / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000378:metabolism; D014018:Tissue Distribution; D059016:Tumor Microenvironment
chemical_list: D006046:Gold
keywords: microvascular density; nanoparticles; renal clearance; tumor acidity; tumor targeting