Enhancement of radiation effect on cancer cells by gold-pHLIP

Antosh, Michael; Wijesinghe, Dayanjali; Shrestha, Samana; Lanou, R.E.; Huang, Yun Hu; Hasselbacher, Thomas; Fox, David J.; Neretti, Nicola; Sun, Shouheng; Katenka, Natallia; Cooper, Leon N.; Andreev, Oleg A.; Reshetnyak, Yana K.

doi:10.1073/pnas.1501628112

Cited by 76 publications

(49 citation statements)

References 42 publications

(53 reference statements)

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“…The pHLIP peptides find a wide range of applications in biomedical sciences 16,20–22,43,44 and, also, they prove to be a very convenient model system for the investigation of polypeptide insertion into the lipid bilayer of a membrane triggered by pH. 12,28 Whereas various spectroscopic methods applied previously probed changes in the conformation of peptides, SAXS employed in this study allowed us, for the first time, to monitor the changes in the liposome and lipid bilayer structure.…”

Section: Discussionmentioning

confidence: 99%

pHLIP Peptide Interaction with a Membrane Monitored by SAXS

et al. 2016

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pH (Low) Insertion Peptides (pHLIP peptides) find application in studies of membrane-associated folding because spontaneous insertion of these peptides is conveniently triggered by varying pH. Here, we employed small-angle X-ray scattering (SAXS) to investigate a wild-type (WT) pHLIP peptide oligomeric state in solution at high concentrations and monitor changes in the liposome structure upon peptide insertion into the bilayer. We established that even at high concentrations (up to 300 µM) the WT pHLIP peptide at pH 8.0 does not form oligomers larger than tetramers (which exhibit concentration-dependent transfer to the monomeric state, as was shown previously). This finding has significance for medical applications when high concentration of the peptide is injected into blood and diluted in blood circulation. The interaction of WT pHLIP peptide with liposomes does not alter the unilamellar vesicle structure upon peptide adsorption by the lipid bilayer at high pH or upon insertion across the bilayer at low pH. At the same time, SAXS data clearly demonstrate the insertion of the peptide into the membrane at low pH, which opens the possibility of investigating the kinetic process of polypeptide insertion and exit from the membrane in real time by time-resolved SAXS.

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Section: Discussionmentioning

confidence: 99%

pHLIP Peptide Interaction with a Membrane Monitored by SAXS

et al. 2016

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“…The radiation enhancement is especially outstanding for gold (Z = 79). Gold has a much higher absorbance of radiation compared to normal tissue with up to a 100‐fold enhancement in the keV energy range …”

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Targeted Gold Nanocluster‐Enhanced Radiotherapy of Prostate Cancer

Luo

Wang

Zeng

et al. 2019

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For over a hundred years, X‐rays have been a main component of the radiotherapeutic approaches to treat cancer. Yet, to date, no radiosensitizer has been developed to selectively target prostate cancer. Gold has excellent X‐ray absorptivity and is used as a radiotherapy enhancing material. In this work, ultrasmall Au25 nanoclusters (NCs) are developed for selective prostate cancer targeting, radiotherapy enhancement, and rapid clearance from the body. Targeted‐Au25 NCs are rapidly and selectively taken up by prostate cancer in vitro and in vivo and also have fast renal clearance. When combined with X‐ray irradiation of the targeted cancer tissues, radiotherapy is significantly enhanced. The selective targeting and rapid clearance of the nanoclusters may allow reductions in radiation dose, decreasing exposure to healthy tissue and making them highly attractive for clinical translation.

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“…Gold nanoparticles have been shown to enhance cancer cell uptake by over 600% at low pH compared with cells treated with gold nanoparticles alone [27], and to promote the internalization of gold nanoparticles in human platelets [69]. Tumor targeting specificity was observed in studies of pHLIP-coated gold nanoclusters, ultimately resulting in the enhancement of radiation effects and increased cytotoxicity [70]. Additionally, pHLIP-coated hollow gold nanospheres (HAuNS) containing chlorin e6 (Ce6), a chemical used to amplify the response of tumor cells to photodynamic therapy, were developed.…”

Section: Applications Of Phlip Technologymentioning

confidence: 99%

Applications of pHLIP Technology for Cancer Imaging and Therapy

Wyatt

Lewis

Andreev

et al. 2017

Trends in Biotechnology

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Acidity is a biomarker of cancer that is not subject to the blunting clonal selection effects that reduce the efficacy of other biomarker technologies, like antibody targeting. The pH (Low) Insertion Peptides (pHLIPs) provide new opportunities for targeting acidic tissues. Through the physical mechanism of membrane-associated folding, pHLIPs are triggered by the acidic microenvironment to insert and span the membranes of tumor cells. The pHLIP platform can be applied to imaging acidic tissues, delivering cell-permeable and impermeable molecules to the cytoplasm, and promoting the cellular uptake of nanoparticles. Since acidosis is a hallmark of tumor development, progression, and aggressiveness, the pHLIP technology may prove useful in targeting cancer cells and metastases for tumor diagnosis, imaging, and therapy.

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Enhancement of radiation effect on cancer cells by gold-pHLIP

Cited by 76 publications

References 42 publications

pHLIP Peptide Interaction with a Membrane Monitored by SAXS

pHLIP Peptide Interaction with a Membrane Monitored by SAXS

Targeted Gold Nanocluster‐Enhanced Radiotherapy of Prostate Cancer

Applications of pHLIP Technology for Cancer Imaging and Therapy

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