Stereocomplexed Poly(lactic acid)−Poly(ethylene glycol) Nanoparticles with Dual-Emissive Boron Dyes for Tumor Accumulation

Kersey, Farrell R.; Zhang, Guoqing; Palmer, Gregory M.; Dewhirst, Mark W.; Fraser, Cassandra L.

doi:10.1021/nn901873t

Cited by 72 publications

(56 citation statements)

References 53 publications

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“…For this reason, the use of intravenous administration has also been considered and we have developed a PEGylated nanoparticle formulation that was found to accumulate near the tumor vasculature using confocal imaging. 28 In conclusion, we have demonstrated and validated techniques by which vascular and tissue oxygenation can be imaged at high spatial and temporal resolution, enabling a detailed understanding of the tumor microenvironment and its influence on tumor gene expression. All these techniques are implemented using a simple modification to a standard fluorescent microscope, enabling a wide range of potential applications.…”

Section: Figmentioning

confidence: 85%

Optical imaging of tumor hypoxia dynamics

et al. 2010

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Abstract. The influence of the tumor microenvironment and hypoxia plays a significant role in determining cancer progression, treatment response, and treatment resistance. That the tumor microenvironment is highly heterogeneous with significant intratumor and intertumor variability presents a significant challenge in developing effective cancer therapies. Critical to understanding the role of the tumor microenvironment is the ability to dynamically quantify oxygen levels in the vasculature and tissue in order to elucidate the roles of oxygen supply and consumption, spatially and temporally. To this end, we describe the use of hyperspectral imaging to characterize hemoglobin absorption to quantify hemoglobin content and oxygen saturation, as well as dual emissive fluorescent/phosphorescent boron nanoparticles, which serve as ratiometric indicators of tissue oxygen tension. Applying these techniques to a window-chamber tumor model illustrates the role of fluctuations in hemoglobin saturation in driving changes in tissue oxygenation, the two being significantly correlated (r = 0.77). Finally, a green-fluorescence-protein reporter for hypoxia inducible factor-1 (HIF-1) provides an endpoint for hypoxic stress in the tumor, which is used to demonstrate a significant association between tumor hypoxia dynamics and HIF-1 activity in an in vivo demonstration of the technique. Tumor hypoxia plays an important role in cancer progression, metastasis, and the effectiveness of therapies.1-3 It is a highly dynamic process and the temporal dynamics can play a significant role in treatment resistance and tumor aggressiveness. 2,4-10A recent trend in therapeutic strategies is to target tumor angiogenesis in order to modify the microenvironment and make tumors more sensitive to conventional therapies.11 The ability to measure pO 2 and image tumor hypoxia on the microscopic level is essential to further understanding microenvironmental factors and modifying therapies, depending on treatment response. Characterizing the local microenvironment, particularly hypoxia, longitudinally, on a microscopic scale would be ideal. This is a challenging problem, however, and one for which no established imaging technique exists. Many methods have been developed that range from histological staining with reducible nitroimidazole reagents, protein markers, and green fluorescence protein (GFP) or luciferase reporter genes, to electrochemical probe methods, and optical, nuclear medicine, and magnetic resonance techniques 12 although some methods are only suitable for the laboratory, others have been translated into the clinic, and all have their advantages and drawbacks. 13,14 The key point is that there is no easily implemented technique for imaging vascular oxygenation (hemoglobin oxygenation) in combination with tissue oxygen tension on the microcirculatory level. We present an approach based on hyperspectral imaging of hemoglobin absorption and dual emissive boron nanoparticles (BNPs). The combination of these techniques enables quantification of...

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Section: Figmentioning

confidence: 85%

Optical imaging of tumor hypoxia dynamics

et al. 2010

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“…Specifically, with BF 2 dbmPLA (dbm = dibenzoylmethane) 10,11,15−19 and its halogenated, heavy atom congener, BF 2 dbm(I)PLA, 14 we demonstrated that emission wavelengths, relative F/P intensities, and oxygen sensitivities are tunable with heavy atom substitution and polymer molecular weight 11,15 and that these materials can be exploited for cellular, 14,15 tissue, and in vivo imaging studies (e.g., tumor hypoxia 14,18 ).…”

Section: Introductionmentioning

confidence: 88%

Dual-Emissive Difluoroboron Naphthyl-Phenyl β-Diketonate Polylactide Materials: Effects of Heavy Atom Placement and Polymer Molecular Weight

et al. 2014

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Luminescent materials are important for imaging and sensing. Aromatic difluoroboron β-diketonate complexes (BF2bdks) are classic fluorescent molecules that have been explored as photochemical reagents, two-photon dyes, and oxygen sensors. A series of BF2bdks with naphthyl and phenyl groups was synthesized, and photophysical properties were investigated in both methylene chloride and poly(lactic acid) (PLA). Polymer molecular weight and dye attachment site along with bromide heavy atom placement were varied to tune optical properties of dye–PLA materials. Systems without heavy atoms have long phosphorescence lifetimes, which is useful for lifetime-based oxygen sensing. Bromine substitution on the naphthyl ring resulted in intense, clearly distinguishable fluorescence and phosphorescence peaks important for ratiometric oxygen sensing and imaging.

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“…It is multi-emissive, exhibiting both short-lived fluorescence (F) and long-lived fluorescence (P) after one-or two-photon excitation. Recently, dual-emissive pegylated BNPs have been fabricated, and they have been shown to have long-circulating, ''stealth''-like properties for studying tumor accumulation and hypoxia imaging in preclinical studies (117).…”

Section: Non-invasive Hypoxia Imagingmentioning

confidence: 99%

Imaging Tumor Hypoxia to Advance Radiation Oncology

Lee

Boss

Dewhirst

2014

Antioxidants & Redox Signaling

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Significance: Most solid tumors contain regions of low oxygenation or hypoxia. Tumor hypoxia has been associated with a poor clinical outcome and plays a critical role in tumor radioresistance. Recent Advances: Two main types of hypoxia exist in the tumor microenvironment: chronic and cycling hypoxia. Chronic hypoxia results from the limited diffusion distance of oxygen, and cycling hypoxia primarily results from the variation in microvessel red blood cell flux and temporary disturbances in perfusion. Chronic hypoxia may cause either tumor progression or regressive effects depending on the tumor model. However, there is a general trend toward the development of a more aggressive phenotype after cycling hypoxia. With advanced hypoxia imaging techniques, spatiotemporal characteristics of tumor hypoxia and the changes to the tumor microenvironment can be analyzed. Critical Issues: In this review, we focus on the biological and clinical consequences of chronic and cycling hypoxia on radiation treatment. We also discuss the advanced non-invasive imaging techniques that have been developed to detect and monitor tumor hypoxia in preclinical and clinical studies. Future Directions: A better understanding of the mechanisms of tumor hypoxia with non-invasive imaging will provide a basis for improved radiation therapeutic practices. Antioxid. Redox Signal. 21, 313-337.

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Stereocomplexed Poly(lactic acid)−Poly(ethylene glycol) Nanoparticles with Dual-Emissive Boron Dyes for Tumor Accumulation

Cited by 72 publications

References 53 publications

Optical imaging of tumor hypoxia dynamics

Optical imaging of tumor hypoxia dynamics

Dual-Emissive Difluoroboron Naphthyl-Phenyl β-Diketonate Polylactide Materials: Effects of Heavy Atom Placement and Polymer Molecular Weight

Imaging Tumor Hypoxia to Advance Radiation Oncology

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