A nanoparticle-based strategy for the imaging of a broad range of tumours by nonlinear amplification of microenvironment signals
Yiguang Wang, Kejin Zhou, Gang Huang, Christopher Hensley, Xiaonan Huang, Xinpeng Ma, Tian Zhao, Baran D Sumer, Ralph J DeBerardinis, Jinming Gao, Yiguang Wang, Kejin Zhou, Gang Huang, Christopher Hensley, Xiaonan Huang, Xinpeng Ma, Tian Zhao, Baran D Sumer, Ralph J DeBerardinis, Jinming Gao
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.
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References
- Stuart MA, et al. Emerging applications of stimuli-responsive polymer materials. Nat. Mater. 2010;9:101–113.
- de Las Heras Alarcon C, Pennadam S, Alexander C. Stimuli responsive polymers for biomedical applications. Chem. Soc. Rev. 2005;34:276–285.
- von Maltzahn G, et al. Nanoparticles that communicate in vivo to amplify tumour targeting. Nat. Mater. 2011;10:545–552.
- Bellomo EG, Wyrsta MD, Pakstis L, Pochan DJ, Deming TJ. Stimuli-responsive polypeptide vesicles by conformation-specific assembly. Nat. Mater. 2004;3:244–248.
- Welsher K, et al. A route to brightly fluorescent carbon nanotubes for near-infrared imaging in mice. Nat. Nanotechnol. 2009;4:773–780.
- So MK, Xu C, Loening AM, Gambhir SS, Rao J. Self-illuminating quantum dot conjugates for in vivo imaging. Nat. Biotechnol. 2006;24:339–343.
- Kircher MF, et al. A brain tumor molecular imaging strategy using a new triple-modality MRI-photoacoustic-Raman nanoparticle. Nat. Med. 2012;18:829–834.
- Qian X, et al. In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags. Nat. Biotechnol. 2008;26:83–90.
- Olson ES, et al. Activatable cell penetrating peptides linked to nanoparticles as dual probes for in vivo fluorescence and MR imaging of proteases. Proc. Natl. Acad. Sci. U. S. A. 2010;107:4311–4316.
- Urano Y, et al. Selective molecular imaging of viable cancer cells with pH-activatable fluorescence probes. Nat. Med. 2009;15:104–109.
- van Dam GM, et al. Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-alpha targeting: first in-human results. Nat. Med. 2011;17:1315–1319.
- Ke S, et al. Near-infrared optical imaging of epidermal growth factor receptor in breast cancer xenografts. Cancer Res. 2003;63:7870–7875.
- Paik S, et al. HER2 and choice of adjuvant chemotherapy for invasive breast cancer: national surgical adjuvant breast and bowel project protocol B-15. J. Natl. Cancer Inst. 2000;92:1991–1998.
- Jacobs TW, Gown AM, Yaziji H, Barnes MJ, Schnitt SJ. HER-2/neu protein expression in breast cancer evaluated by immunohistochemistry. A study of interlaboratory agreement. Am. J. Clin. Pathol. 2000;113:251–258.
- Weis SM, Cheresh DA. Tumor angiogenesis: molecular pathways and therapeutic targets. Nat. Med. 2011;17:1359–1370.
- Folkman J. Angiogenesis: an organizing principle for drug discovery? Nat. Rev. Drug Discovery. 2007;6:273–286.
- Webb BA, Chimenti M, Jacobson MP, Barber DL. Dysregulated pH: a perfect storm for cancer progression. Nat. Rev. Cancer. 2011;11:671–677.
- Zhou K, et al. Tunable, ultrasensitive pH-responsive nanoparticles targeting specific endocytic organelles in living cells. Angew. Chem. Int. Ed. 2011;50:6109–6114.
- Bachelder EM, Beaudette TT, Broaders KE, Dashe J, Frechet JM. Acetal-derivatized dextran: an acid-responsive biodegradable material for therapeutic applications. J. Am. Chem. Soc. 2008;130:10494–10495.
- Bae Y, Fukushima S, Harada A, Kataoka K. Design of environment-sensitive supramolecular assemblies for intracellular drug delivery: polymeric micelles that are responsive to intracellular pH change. Angew. Chem. Int. Ed. 2003;42:4640–4643.
- Griset AP, et al. Expansile Nanoparticles: Synthesis, Characterization, and in Vivo Efficacy of an Acid-Responsive Polymeric Drug Delivery System. J. Am. Chem. Soc. 2009;131:2469–2471.
- Lee ES, Na K, Bae YH. Super pH-sensitive multifunctional polymeric micelle. Nano Lett. 2005;5:325–329.
- Potineni A, Lynn DM, Langer R, Amiji MM. Poly(ethylene oxide)-modified poly(beta-amino ester) nanoparticles as a pH-sensitive biodegradable system for paclitaxel delivery. J. Control. Release. 2003;86:223–234.
- Zhou K, et al. Multicolored pH-tunable and activatable fluorescence nanoplatform responsive to physiologic pH stimuli. J. Am. Chem. Soc. 2012;134:7803–7811.
- Sonveaux P, et al. Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice. J. Clin. Invest. 2008;118:3930–3942.
- Maeda H, Wu J, Sawa T, Matsumura Y, Hori K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J. Control. Release. 2000;65:271–284.
- Gatenby RA, Gillies RJ. Why do cancers have high aerobic glycolysis? Nat. Rev. Cancer. 2004;4:891–899.
- Kleiter MM, et al. A comparison of oral and intravenous pimonidazole in canine tumors using intravenous CCI-103F as a control hypoxia marker. Int. J. Radiat. Oncol. Biol. Phys. 2006;64:592–602.
- Huang X, et al. A reexamination of active and passive tumor targeting by using rod-shaped gold nanocrystals and covalently conjugated peptide ligands. ACS Nano. 2010;4:5887–5896.
- Moghimi SM, Hedeman H, Muir IS, Illum L, Davis SS. An Investigation of the Filtration Capacity and the Fate of Large Filtered Sterically-Stabilized Microspheres in Rat Spleen. Biochim. Biophys. Acta. 1993;1157:233–240.
- Polyak K. Heterogeneity in breast cancer. J. Clin. Invest. 2011;121:3786–3788.
- Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324:1029–1033.
- Dhanabal M, et al. Endostatin induces endothelial cell apoptosis. J. Biol. Chem. 1999;274:11721–11726.
- Folkman J. What is the evidence that tumors are angiogenesis dependent? J. Natl. Cancer Inst. 1990;82:4–6.
- Nasongkla N, et al. Multifunctional polymeric micelles as cancer-targeted, MRI-ultrasensitive drug delivery systems. Nano Lett. 2006;6:2427–2430.
Source: PubMed