@article{pmid36349615,

title = {A Pt(IV)-conjugated brain penetrant macrocyclic peptide shows pre-clinical efficacy in glioblastoma},

author = {J L Jimenez-Macias and Y-C Lee and E Miller and T Finkelberg and M Zdioruk and G Berger and C E Farquhar and M O Nowicki and C-F Cho and B I Fedeles and A Loas and B L Pentelute and S E Lawler},

doi = {10.1016/j.jconrel.2022.10.051},

issn = {1873-4995},

year  = {2022},

date = {2022-12-01},

journal = {J Control Release},

volume = {352},

pages = {623--636},

abstract = {Glioblastoma (GBM) is the most aggressive primary malignant brain tumor, with a median survival of approximately 15 months. Treatment is limited by the blood-brain barrier (BBB) which restricts the passage of most drugs to the brain. We previously reported the design and synthesis of a BBB-penetrant macrocyclic cell-penetrating peptide conjugate (M13) covalently linked at the axial position of a Pt(IV) cisplatin prodrug. Here we show the Pt(IV)-M13 conjugate releases active cisplatin upon intracellular reduction and effects potent in vitro GBM cell killing. Pt(IV)-M13 significantly increased platinum uptake in an in vitro BBB spheroid model and intravenous administration of Pt(IV)-M13 in GBM tumor-bearing mice led to higher platinum levels in brain tissue and intratumorally compared with cisplatin. Pt(IV)-M13 administration was tolerated in naïve nude mice at higher dosage regimes than cisplatin and significantly extended survival above controls in a murine GBM xenograft model (median survival 33 days for Pt(IV)-M13 vs 24 days for Pt(IV) prodrug, 22.5 days for cisplatin and 22 days for control). Increased numbers of γH2AX nuclear foci, biomarkers of DNA damage, were observed in tumors of Pt(IV)-M13-treated mice, consistent with elevated platinum levels. The present work provides the first demonstration that systemic injection of a Pt(IV) complex conjugated to a brain-penetrant macrocyclic peptide can lead to increased platinum levels in the brain and extend survival in mouse GBM models, supporting further development of this approach and the utility of brain-penetrating macrocyclic peptide conjugates for delivering non-BBB penetrant drugs to the central nervous system.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{697827,

title = {Variants of the adeno-associated virus serotype 9 with enhanced penetration of the blood-brain barrier in rodents and primates.},

author = {Yizheng Yao and Jun Wang and Yi Liu and Yuan Qu and Kai Kai Wang and Yang Zhang and Yuxin Chang and Zhi Yang and Jie Wan and Junfeng Liu and Hiroshi Nakashima and Sean E Lawler and E Antonio Chiocca and Choi-Fong Cho and Fengfeng Bei},

year  = {2022},

date = {2022-01-01},

journal = {Nature Biomedical Engineering},

volume = {6},

number = {11},

pages = {1257-1271},

abstract = {The development of gene therapies for the treatment of diseases of the central nervous system has been hindered by the limited availability of adeno-associated viruses (AAVs) that efficiently traverse the blood-brain barrier (BBB). Here, we report the rational design of AAV9 variants displaying cell-penetrating peptides on the viral capsid and the identification of two variants, AAV.CPP.16 and AAV.CPP.21, with improved transduction efficiencies of cells of the central nervous system on systemic delivery (6- to 249-fold across 4 mouse strains and 5-fold in cynomolgus macaques, with respect to the AAV9 parent vector). We also show that the neurotropism of AAV.CPP.16 is retained in young and adult macaques, that this variant displays enhanced transcytosis at the BBB as well as increased efficiency of cellular transduction relative to AAV9, and that it can be used to deliver antitumour payloads in a mouse model of glioblastoma. AAV capsids that can efficiently penetrate the BBB will facilitate the clinical translation of gene therapies aimed at the central nervous system.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{691264,

title = {A Tumor-Homing Peptide Platform Enhances Drug Solubility, Improves Blood-Brain Barrier Permeability and Targets Glioblastoma.},

author = {Choi-Fong Cho and Charlotte E. Farquhar and Colin M. Fadzen and Benjamin Scott and Pei Zhuang and Niklas Spreckelsen and Andrei Loas and Nina Hartrampf and Bradley L. Pentelute and Sean E. Lawler},

url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9103942/},

year  = {2022},

date = {2022-01-01},

journal = {Cancers},

volume = {14},

number = {9},

pages = {2207},

abstract = {Background: Glioblastoma (GBM) is the most common and deadliest malignant primary brain tumor, contributing significant morbidity and mortality among patients. As current standard-of-care demonstrates limited success, the development of new efficacious GBM therapeutics is urgently needed. Major challenges in advancing GBM chemotherapy include poor bioavailability, lack of tumor selectivity leading to undesired side effects, poor permeability across the blood–brain barrier (BBB), and extensive intratumoral heterogeneity. Methods: We have previously identified a small, soluble peptide (BTP-7) that is able to cross the BBB and target the human GBM extracellular matrix (ECM). Here, we covalently attached BTP-7 to an insoluble anti-cancer drug, camptothecin (CPT). Results: We demonstrate that conjugation of BTP-7 to CPT improves drug solubility in aqueous solution, retains drug efficacy against patient-derived GBM stem cells (GSC), enhances BBB permeability, and enables therapeutic targeting to intracranial GBM, leading to higher toxicity in GBM cells compared to normal brain tissues, and ultimately prolongs survival in mice bearing intracranial patient-derived GBM xenograft. Conclusion: BTP-7 is a new modality that opens the door to possibilities for GBM-targeted therapeutic approaches.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{669244,

title = {Targeting Glioblastoma Using a Novel Peptide Specific to a Deglycosylated Isoform of Brevican},

author = {Niklas Spreckelsen and Colin M. Fadzen and Nina Hartrampf and Yarah Ghotmi and Justin M. Wolfe and Shipra Dubey and Bo Yeun Yang and Marie F. Kijewski and Shuyan Wang and Charlotte Farquhar and Sonja Bergmann and Mykola Zdioruk and J. Roscoe Wasserburg and Benjamin Scott and Emily Murrell and Fernanda C. Bononi and Leonard G. Luyt and Marcelo DiCarli and Martine L. M. Lamfers and Keith L. Ligon and E. Antonio Chiocca and Mariano S. Viapiano and Bradley L. Pentelute and Sean E. Lawler and Choi-Fong Cho},

url = {https://onlinelibrary.wiley.com/doi/10.1002/adtp.202000244},

year  = {2021},

date = {2021-01-01},

journal = {Advanced Therapeutics},

volume = {4},

pages = {2000244},

abstract = {Glioblastoma (GBM) is the most common and deadliest form of brain tumor and remains amongst the most difficult cancers to treat. Brevican (Bcan), a central nervous system (CNS)-specific extracellular matrix protein, is upregulated in high-grade glioma cells, including GBM. A Bcan isoform lacking most glycosylation, dg-Bcan, is found only in GBM tissues. Here, dg-Bcan is explored as a molecular target for GBM. In this study, a d-peptide library is screened to identify a small 8-amino acid dg-Bcan-Targeting Peptide (BTP) candidate, called BTP-7 that binds dg-Bcan with high affinity and specificity. BTP-7 is preferentially internalized by dg-Bcan-expressing patient-derived GBM cells. To demonstrate GBM targeting, BTP-7 is radiolabeled with 18F, a radioisotope of fluorine, and increased radiotracer accumulation is found in intracranial GBM established in mice using positron emission tomography (PET) imaging. dg-Bcan is an attractive molecular target for GBM, and BTP-7 represents a promising lead candidate for further development into novel imaging agents and targeted therapeutics.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{667306,

title = {A Platinum(IV) Prodrug-Perfluoroaryl Macrocyclic Peptide Conjugate Enhances Platinum Uptake in the Brain},

author = {Colin M Fadzen and Justin M Wolfe and Wen Zhou and Choi-Fong Cho and Niklas Spreckelsen and Kathryn T Hutchinson and Yen-Chun Lee and E Antonio Chiocca and Sean E Lawler and Omer H Yilmaz and Stephen J Lippard and Bradley L Pentelute},

year  = {2020},

date = {2020-01-01},

journal = {Journal of Medicinal Chemistry},

volume = {63},

pages = {6741},

abstract = {Effective delivery to the brain limits the development of novel glioblastoma therapies. Here, we introduce conjugation between platinum(IV) prodrugs of cisplatin and perfluoroaryl peptide macrocycles to increase brain uptake. We demonstrate that one such conjugate shows efficacy against glioma stem-like cells. We investigate the pharmacokinetics of this conjugate in mice and show that the amount of platinum in the brain after treatment with the conjugate is 15-fold greater than with cisplatin after 5 h.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid30382243,

title = {Blood-brain-barrier organoids for investigating the permeability of CNS therapeutics},

author = {Sonja Bergmann and Sean E Lawler and Yuan Qu and Colin M Fadzen and Justin M Wolfe and Michael S Regan and Bradley L Pentelute and Nathalie Y R Agar and Choi-Fong Cho},

doi = {10.1038/s41596-018-0066-x},

issn = {1750-2799},

year  = {2018},

date = {2018-12-01},

journal = {Nat Protoc},

volume = {13},

number = {12},

pages = {2827--2843},

abstract = {In vitro models of the blood-brain barrier (BBB) are critical tools for the study of BBB transport and the development of drugs that can reach the CNS. Brain endothelial cells grown in culture are often used to model the BBB; however, it is challenging to maintain reproducible BBB properties and function. 'BBB organoids' are obtained following coculture of endothelial cells, pericytes and astrocytes under low-adhesion conditions. These organoids reproduce many features of the BBB, including the expression of tight junctions, molecular transporters and drug efflux pumps, and hence can be used to model drug transport across the BBB. This protocol provides a comprehensive description of the techniques required to culture and maintain BBB organoids. We also describe two separate detection approaches that can be used to analyze drug penetration into the organoids: confocal fluorescence microscopy and mass spectrometry imaging. Using our protocol, BBB organoids can be established within 2-3 d. An additional day is required to analyze drug permeability. The BBB organoid platform represents an accurate, versatile and cost-effective in vitro tool. It can easily be scaled to a high-throughput format, offering a tool for BBB modeling that could accelerate therapeutic discovery for the treatment of various neuropathologies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid28992407,

title = {Perfluoroarene-Based Peptide Macrocycles to Enhance Penetration Across the Blood-Brain Barrier},

author = {Colin M Fadzen and Justin M Wolfe and Choi-Fong Cho and E Antonio Chiocca and Sean E Lawler and Bradley L Pentelute},

doi = {10.1021/jacs.7b09790},

issn = {1520-5126},

year  = {2017},

date = {2017-11-01},

journal = {J Am Chem Soc},

volume = {139},

number = {44},

pages = {15628--15631},

abstract = {Here we describe the utility of peptide macrocyclization through perfluoroaryl-cysteine SAr chemistry to improve the ability of peptides to cross the blood-brain barrier. Multiple macrocyclic analogues of the peptide transportan-10 were investigated that displayed increased uptake in two different cell lines and improved proteolytic stability. One of these analogues (M13) exhibited substantially increased delivery across a cellular spheroid model of the blood-brain barrier. Through ex vivo imaging of mouse brains, we demonstrated that this perfluoroarene-based macrocycle of TP10 exhibits increased penetration of the brain parenchyma following intravenous administration in mice. Finally, we evaluated macrocyclic analogues of the BH3 domain of the BIM protein to assess if our approach would be applicable to a peptide of therapeutic interest. We identified a BIM BH3 analogue that showed increased penetration of the brain tissue in mice.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid28799610,

title = {Viral nanoparticles decorated with novel EGFL7 ligands enable intravital imaging of tumor neovasculature},

author = {Choi-Fong Cho and Lihai Yu and Tienabe K Nsiama and Alisha N Kadam and Arun Raturi and Sourabh Shukla and Giulio A Amadei and Nicole F Steinmetz and Leonard G Luyt and John D Lewis},

doi = {10.1039/c7nr02558k},

issn = {2040-3372},

year  = {2017},

date = {2017-08-01},

journal = {Nanoscale},

volume = {9},

number = {33},

pages = {12096--12109},

abstract = {Angiogenesis is a dynamic process fundamental to the development of solid tumors. Epidermal growth factor-like domain 7 (EGFL7) is a protein whose expression is restricted to endothelial cells undergoing active remodeling that has emerged as a key mediator of this process. EGFL7 expression is associated with poor outcome in several cancers, making it a promising target for imaging or therapeutic strategies. Here, EGFL7 is explored as a molecular target for active neovascularization. Using a combinatorial peptide screening approach, we describe the discovery and characterization of a novel high affinity EGFL7-binding peptide, E7p72, that specifically targets human endothelial cells. Viral nanoparticles decorated with E7p72 peptides specifically target tumor-associated neovasculature with high specificity as assessed by intravital imaging. This work highlights the value of EGFL7 as a target for angiogenic vessels and opens the door for novel targeted therapeutic approaches.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lawler2017,

title = {Oncolytic Viruses in Cancer Treatment},

author = {Sean E. Lawler and Maria-Carmela Speranza and Choi-Fong Cho and E. Antonio Chiocca},

doi = {10.1001/jamaoncol.2016.2064},

issn = {2374-2437},

year  = {2017},

date = {2017-06-01},

journal = {JAMA Oncol},

volume = {3},

number = {6},

publisher = {American Medical Association (AMA)},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid28585535,

title = {Blood-brain-barrier spheroids as an in vitro screening platform for brain-penetrating agents},

author = {Choi-Fong Cho and Justin M Wolfe and Colin M Fadzen and David Calligaris and Kalvis Hornburg and E Antonio Chiocca and Nathalie Y R Agar and Bradley L Pentelute and Sean E Lawler},

doi = {10.1038/ncomms15623},

issn = {2041-1723},

year  = {2017},

date = {2017-06-01},

journal = {Nat Commun},

volume = {8},

pages = {15623},

abstract = {Culture-based blood-brain barrier (BBB) models are crucial tools to enable rapid screening of brain-penetrating drugs. However, reproducibility of in vitro barrier properties and permeability remain as major challenges. Here, we report that self-assembling multicellular BBB spheroids display reproducible BBB features and functions. The spheroid core is comprised mainly of astrocytes, while brain endothelial cells and pericytes encase the surface, acting as a barrier that regulates transport of molecules. The spheroid surface exhibits high expression of tight junction proteins, VEGF-dependent permeability, efflux pump activity and receptor-mediated transcytosis of angiopep-2. In contrast, the transwell co-culture system displays comparatively low levels of BBB regulatory proteins, and is unable to discriminate between the transport of angiopep-2 and a control peptide. Finally, we have utilized the BBB spheroids to screen and identify BBB-penetrant cell-penetrating peptides (CPPs). This robust in vitro BBB model could serve as a valuable next-generation platform for expediting the development of CNS therapeutics.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid27124678,

title = {Design of a Microfluidic Chip for Magnetic-Activated Sorting of One-Bead-One-Compound Libraries},

author = {Choi-Fong Cho and Kyungheon Lee and Maria-Carmela Speranza and Fernanda C Bononi and Mariano S Viapiano and Leonard G Luyt and Ralph Weissleder and E Antonio Chiocca and Hakho Lee and Sean E Lawler},

doi = {10.1021/acscombsci.5b00180},

issn = {2156-8944},

year  = {2016},

date = {2016-06-01},

journal = {ACS Comb Sci},

volume = {18},

number = {6},

pages = {271--278},

abstract = {Molecular targeting using ligands specific to disease markers has shown great promise for early detection and directed therapy. Bead-based combinatorial libraries have served as powerful tools for the discovery of novel targeting agents. Screening platforms employing magnetic capture have been used to achieve rapid and efficient identification of high-affinity ligands from one-bead-one-compound (OBOC) libraries. Traditional manual methodologies to isolate magnetized "hit" beads are tedious and lack accuracy, and existing instruments to expedite bead sorting tend to be costly and complex. Here, we describe the design and construction of a simple and inexpensive microfluidic magnetic sorting device using standard photolithography and soft lithography approaches to facilitate high-throughput isolation of magnetized positive hit beads from combinatorial libraries. We have demonstrated that the device is able to sort magnetized beads with superior accuracy compared to conventional manual sorting approaches. This chip offers a very convenient yet inexpensive alternative for screening OBOC libraries.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid26846842,

title = {BKM-120 (Buparlisib): A Phosphatidyl-Inositol-3 Kinase Inhibitor with Anti-Invasive Properties in Glioblastoma},

author = {Maria-Carmela Speranza and Michal O Nowicki and Prajna Behera and Choi-Fong Cho and E Antonio Chiocca and Sean E Lawler},

doi = {10.1038/srep20189},

issn = {2045-2322},

year  = {2016},

date = {2016-02-01},

journal = {Sci Rep},

volume = {6},

pages = {20189},

abstract = {Glioblastoma is an aggressive, invasive tumor of the central nervous system (CNS). There is a widely acknowledged need for anti-invasive therapeutics to limit glioblastoma invasion. BKM-120 is a CNS-penetrant pan-class I phosphatidyl-inositol-3 kinase (PI3K) inhibitor in clinical trials for solid tumors, including glioblastoma. We observed that BKM-120 has potent anti-invasive effects in glioblastoma cell lines and patient-derived glioma cells in vitro. These anti-migratory effects were clearly distinguishable from cytostatic and cytotoxic effects at higher drug concentrations and longer durations of drug exposure. The effects were reversible and accompanied by changes in cell morphology and pronounced reduction in both cell/cell and cell/substrate adhesion. In vivo studies showed that a short period of treatment with BKM-120 slowed tumor spread in an intracranial xenografts. GDC-0941, a similar potent and selective PI3K inhibitor, only caused a moderate reduction in glioblastoma cell migration. The effects of BKM-120 and GDC-0941 were indistinguishable by in vitro kinase selectivity screening and phospho-protein arrays. BKM-120 reduced the numbers of focal adhesions and the velocity of microtubule treadmilling compared with GDC-0941, suggesting that mechanisms in addition to PI3K inhibition contribute to the anti-invasive effects of BKM-120. Our data suggest the CNS-penetrant PI3K inhibitor BKM-120 may have anti-invasive properties in glioblastoma.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{667260,

title = {Experimental therapies: gene therapies and oncolytic viruses},

author = {M Maher Hulou and Choi-Fong Cho and E Antonio Chiocca and Rolf Bjerkvig},

year  = {2016},

date = {2016-01-01},

journal = {Handbook of Clinical Neurology},

volume = {134},

pages = {183},

abstract = {Glioblastoma is the most common and aggressive primary brain tumor in adults. Over the past three decades, the overall survival time has only improved by a few months, therefore novel alternative treatment modalities are needed to improve clinical management strategies. Such strategies should ultimately extend patient survival. At present, the extensive insight into the molecular biology of gliomas, as well as into genetic engineering techniques, has led to better decision processes when it comes to modifying the genome to accommodate suicide genes, cytokine genes, and tumor suppressor genes that may kill cancer cells, and boost the host defensive immune system against neoantigenic cytoplasmic and nuclear targets. Both nonreplicative viral vectors and replicating oncolytic viruses have been developed for brain cancer treatment. Stem cells, microRNAs, nanoparticles, and viruses have also been designed. These have been armed with transgenes or peptides, and have been used both in laboratory-based experiments as well as in clinical trials, with the aim of improving selective killing of malignant glioma cells while sparing normal brain tissue. This chapter reviews the current status of gene therapies for malignant gliomas and highlights the most promising viral and cell-based strategies under development.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid26456171,

title = {Identification, design and synthesis of tubulin-derived peptides as novel hyaluronan mimetic ligands for the receptor for hyaluronan-mediated motility (RHAMM/HMMR)},

author = {Kenneth Virgel N Esguerra and Cornelia Tolg and Natalia Akentieva and Matthew Price and Choi-Fong Cho and John D Lewis and James B McCarthy and Eva A Turley and Leonard G Luyt},

doi = {10.1039/c5ib00222b},

issn = {1757-9708},

year  = {2015},

date = {2015-12-01},

journal = {Integr Biol (Camb)},

volume = {7},

number = {12},

pages = {1547--1560},

abstract = {Fragments of the extracellular matrix component hyaluronan (HA) promote tissue inflammation, fibrosis and tumor progression. HA fragments act through HA receptors including CD44, LYVE1, TLR2, 4 and the receptor for hyaluronan mediated motility (RHAMM/HMMR). RHAMM is a multifunctional protein with both intracellular and extracellular roles in cell motility and proliferation. Extracellular RHAMM binds directly to HA fragments while intracellular RHAMM binds directly to ERK1 and tubulin. Both HA and regions of tubulin (s-tubulin) are anionic and bind to basic amino acid-rich regions in partner proteins, such as in HA and tubulin binding regions of RHAMM. We used this as a rationale for developing bioinformatics and SPR (surface plasmon resonance) based screening to identify high affinity anionic RHAMM peptide ligands. A library of 12-mer peptides was prepared based on the carboxyl terminal tail sequence of s-tubulin isoforms and assayed for their ability to bind to the HA/tubulin binding region of recombinant RHAMM using SPR. This approach resulted in the isolation of three 12-mer peptides with nanomolar affinity for RHAMM. These peptides bound selectively to RHAMM but not to CD44 or TLR2,4 and blocked RHAMM:HA interactions. Furthermore, fluorescein-peptide uptake by PC3MLN4 prostate cancer cells was blocked by RHAMM mAb but not by CD44 mAb. These peptides also reduced the ability of prostate cancer cells to degrade collagen type I. The selectivity of these novel HA peptide mimics for RHAMM suggest their potential for development as HA mimetic imaging and therapeutic agents for HA-promoted disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid24243252,

title = {Molecular targeted viral nanoparticles as tools for imaging cancer},

author = {Choi-Fong Cho and Sourabh Shukla and Emily J Simpson and Nicole F Steinmetz and Leonard G Luyt and John D Lewis},

doi = {10.1007/978-1-62703-751-8_16},

issn = {1940-6029},

year  = {2014},

date = {2014-01-01},

journal = {Methods Mol Biol},

volume = {1108},

pages = {211--230},

abstract = {Viral nanoparticles (VNPs) are a novel class of bionanomaterials that harness the natural biocompatibility of viruses for the development of therapeutics, vaccines, and imaging tools. The plant virus, cowpea mosaic virus (CPMV), has been successfully engineered to create novel cancer-targeted imaging agents by incorporating fluorescent dyes, polyethylene glycol (PEG) polymers, and targeting moieties. Using straightforward conjugation strategies, VNPs with high selectivity for cancer-specific molecular targets can be synthesized for in vivo imaging of tumors. Here we describe the synthesis and purification of CPMV-based VNPs, the functionalization of these VNPs using click chemistry, and their use for imaging xenograft tumors in animal models. VNPs decorated with fluorescent dyes, PEG, and targeting ligands can be synthesized in one day, and imaging studies can be performed over hours, days, or weeks, depending on the application.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid23819541,

title = {High-throughput screening of one-bead-one-compound peptide libraries using intact cells},

author = {Choi-Fong Cho and Babak Behnam Azad and Leonard G Luyt and John D Lewis},

doi = {10.1021/co4000584},

issn = {2156-8944},

year  = {2013},

date = {2013-08-01},

journal = {ACS Comb Sci},

volume = {15},

number = {8},

pages = {393--400},

abstract = {Screening approaches based on one-bead-one-compound (OBOC) combinatorial libraries have facilitated the discovery of novel peptide ligands for cellular targeting in cancer and other diseases. Recognition of cell surface proteins is optimally achieved using live cells, yet screening intact cell populations is time-consuming and inefficient. Here, we evaluate the Complex Object Parametric Analyzer and Sorter (COPAS) large particle biosorter for high-throughput sorting of bead-bound human cell populations. When a library of RGD-containing peptides was screened against human cancer cells that express αvβ3 integrin, it was found that bead-associated cells are rapidly dissociated when sorted through the COPAS instrument. When the bound cells were reversibly cross-linked onto the beads, however, we demonstrated that cell/bead mixtures can be sorted quickly and accurately. This reversible cross-linking approach is compatible with matrix-assisted laser desorption ionization time-of-flight mass spectrometry-based peptide sequence deconvolution. This approach should allow one to rapidly screen an OBOC library and identify novel peptide ligands against cell surface targets in their native conformation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Cho2012,

title = {Discovery of Novel Integrin Ligands from Combinatorial Libraries Using a Multiplex “Beads on a Bead” Approach},

author = {Choi-Fong Cho and Giulio A. Amadei and Daniel Breadner and Leonard G. Luyt and John D. Lewis},

doi = {10.1021/nl3034043},

issn = {1530-6992},

year  = {2012},

date = {2012-11-14},

journal = {Nano Lett.},

volume = {12},

number = {11},

pages = {5957--5965},

publisher = {American Chemical Society (ACS)},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{BehnamAzad2012,

title = {Synthesis, radiometal labeling and in vitro evaluation of a targeted PPIX derivative},

author = {Babak Behnam Azad and Choi-Fong Cho and John D. Lewis and Leonard G. Luyt},

doi = {10.1016/j.apradiso.2011.11.054},

issn = {0969-8043},

year  = {2012},

date = {2012-03-00},

journal = {Applied Radiation and Isotopes},

volume = {70},

number = {3},

pages = {505--511},

publisher = {Elsevier BV},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid21730939,

title = {Evaluation of nanoparticle uptake in tumors in real time using intravital imaging},

author = {Choi-Fong Cho and Amber Ablack and Hon-Sing Leong and Andries Zijlstra and John Lewis},

doi = {10.3791/2808},

issn = {1940-087X},

year  = {2011},

date = {2011-06-01},

journal = {J Vis Exp},

number = {52},

abstract = {Current technologies for tumor imaging, such as ultrasound, MRI, PET and CT, are unable to yield high-resolution images for the assessment of nanoparticle uptake in tumors at the microscopic level(1,2,3,) highlighting the utility of a suitable xenograft model in which to perform detailed uptake analyses. Here, we use high-resolution intravital imaging to evaluate nanoparticle uptake in human tumor xenografts in a modified, shell-less chicken embryo model. The chicken embryo model is particularly well-suited for these in vivo analyses because it supports the growth of human tumors, is relatively inexpensive and does not require anesthetization or surgery 4,5. Tumor cells form fully vascularized xenografts within 7 days when implanted into the chorioallantoic membrane (CAM)( 6). The resulting tumors are visualized by non-invasive real-time, high-resolution imaging that can be maintained for up to 72 hours with little impact on either the host or tumor systems. Nanoparticles with a wide range of sizes and formulations administered distal to the tumor can be visualized and quantified as they flow through the bloodstream, extravasate from leaky tumor vasculature, and accumulate at the tumor site. We describe here the analysis of nanoparticles derived from Cowpea mosaic virus (CPMV) decorated with near-infrared fluorescent dyes and/or polyethylene glycol polymers (PEG) (7, 8, 9,10,11). Upon intravenous administration, these viral nanoparticles are rapidly internalized by endothelial cells, resulting in global labeling of the vasculature both outside and within the tumor(7,12). PEGylation of the viral nanoparticles increases their plasma half-life, extends their time in the circulation, and ultimately enhances their accumulation in tumors via the enhanced permeability and retention (EPR) effect (7, 10,11). The rate and extent of accumulation of nanoparticles in a tumor is measured over time using image analysis software. This technique provides a method to both visualize and quantify nanoparticle dynamics in human tumors.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid21385137,

title = {Cowpea mosaic virus nanoparticles target surface vimentin on cancer cells},

author = {Nicole F Steinmetz and Choi-Fong Cho and Amber Ablack and John D Lewis and Marianne Manchester},

doi = {10.2217/nnm.10.136},

issn = {1748-6963},

year  = {2011},

date = {2011-02-01},

journal = {Nanomedicine (Lond)},

volume = {6},

number = {2},

pages = {351--364},

abstract = {AIMS: Vimentin, a type III intermediate filament, is upregulated during epithelial-mesenchymal transition and tumor progression. Vimentin is surface-expressed on cells involved in inflammation; the function remains unknown. We investigated the expression of surface vimentin on cancer cells and evaluated targeting nanoparticles to tumors exploiting vimentin.nnMATERIALS & METHODS: Cowpea mosaic virus nanoparticles that interact with surface vimentin were used as probes. Tumor homing was tested using the chick chorioallantoic membrane model with human tumor xenografts.nnRESULTS & DISCUSSION: Surface vimentin levels varied during cell cycle and among the cell lines tested. Surface vimentin expression correlated with cowpea mosaic virus uptake, underscoring the utility of cowpea mosaic virus to detect invasive cancer cells. Targeting to tumor xenografts was observed; homing was based on the enhanced permeability and retention effect. Our data provide novel insights into the role of surface vimentin in cancer and targeting nanoparticles in vivo.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{667327,

title = {A fast, reproducible and low-cost method for sequence deconvolution of ’on-bead’ peptides via ’on-target’ maldi-TOF/TOF mass spectrometry},

author = {Giulio A Amadei and Choi-Fong Cho and John D Lewis and Leonard G Luyt},

year  = {2010},

date = {2010-01-01},

journal = {Journal of Mass Spectrometry},

volume = {45},

pages = {241},

abstract = {A novel approach to high-throughput sequence deconvolution of on-bead small peptides (MW < 2000 Da) using on-target MALDI-TOF/TOF instrumentation is presented. Short peptides of pentamer and octamer length, covalently attached to TentaGel polystyrene beads through a photolabile linker, were placed onto the MALDI target, apportioned with suitable matrix (2,5-dihydroxybenzoic acid) and then hit with the instrument laser (Nd : YAG, 355 nm). This induced easy and highly reproducible photochemical cleavage, desorption (MS mode) and fragmentation (MS/MS mode). Peptide fragments were identified with a mass accuracy of 0.1 Da of the expected values. This technique significantly accelerates the sequence determination of positive peptide hits obtained from random combinatorial libraries when screening against biological targets, paving the way for a rapid and efficient method to identify molecular imaging ligands specific to pathological targets in cancer and other diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}