title: A nanoparticle-based strategy for the imaging of a broad range of tumours by nonlinear amplification of microenvironment signals.
abstract: Stimuli-responsive nanomaterials are increasingly important in a variety of applications such as biosensing, molecular imaging, drug delivery and tissue engineering. For cancer detection, a paramount challenge still exists in the search for methods that can illuminate tumours universally regardless of their genotypes and phenotypes. Here we capitalized on the acidic, angiogenic tumour microenvironment to achieve the detection of tumour tissues in a wide variety of mouse cancer models. This was accomplished using ultra pH-sensitive fluorescent nanoprobes that have tunable, exponential fluorescence activation on encountering subtle, physiologically relevant pH transitions. These nanoprobes were silent in the circulation, and then strongly activated (>300-fold) in response to the neovasculature or to the low extracellular pH in tumours. Thus, we have established non-toxic, fluorescent nanoreporters that can nonlinearly amplify tumour microenvironmental signals, permitting the identification of tumour tissue independently of histological type or driver mutation, and detection of acute treatment responses much more rapidly than conventional imaging approaches.
authors: Department of Pharmacology, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.
authors: Yiguang
authors: Y
authors: Wang
authors: Department of Pharmacology, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.
authors: Kejin
authors: K
authors: Zhou
authors: Department of Pharmacology, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.
authors: Gang
authors: G
authors: Huang
authors: Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.
authors: Christopher
authors: C
authors: Hensley
authors: Department of Pharmacology, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.
authors: Xiaonan
authors: X
authors: Huang
authors: Department of Pharmacology, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.
authors: Xinpeng
authors: X
authors: Ma
authors: Department of Pharmacology, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.
authors: Tian
authors: T
authors: Zhao
authors: Department of Otolaryngology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.
authors: Baran D
authors: BD
authors: Sumer
authors: Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.
authors: Ralph J
authors: RJ
authors: DeBerardinis
authors: Department of Pharmacology, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.
authors: Jinming
authors: J
authors: Gao
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry; D007089:Image Enhancement / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence / Q000379:methods*; D057054:Molecular Imaging / Q000379:methods*; D053769:Nanocapsules / Q000737:chemistry; D009374:Neoplasms, Experimental / Q000473:pathology*; D017711:Nonlinear Dynamics; D059016:Tumor Microenvironment
chemical_list: D005456:Fluorescent Dyes; D053769:Nanocapsules