Enhanced tumor delivery and antitumor activity in vivo of liposomal doxorubicin modified with MCF-7-specific phage fusion protein

Wang, Tao; Hartner, William C.; Gillespie, James W.; Kulkarni, Praveen; Yang, Shiyong; Mei, Leslie A.; Petrenko, Valery A.; Torchilin, Vladimir P.

doi:10.1016/j.nano.2013.08.009

Cited by 53 publications

(49 citation statements)

References 39 publications

(46 reference statements)

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“…Phages were propagated and isolated as described previously (17, 21). Briefly, phages were subjected to a series of processes including endotoxin removal, PEG-precipitation and structure disassembly by the incubation with sodium cholate.…”

Section: Methodsmentioning

confidence: 99%

Paclitaxel-Loaded PEG-PE–Based Micellar Nanopreparations Targeted with Tumor-Specific Landscape Phage Fusion Protein Enhance Apoptosis and Efficiently Reduce Tumors

Wang

Yang

Mei

et al. 2014

Molecular Cancer Therapeutics

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In an effort to improve the therapeutic index of cancer chemotherapy, we developed an advanced nanopreparation based on the combination of landscape phage display to obtain new targeting ligands with micellar nanoparticles for tumor targeting of water insoluble neoplastic agents. With paclitaxel as a drug, this self-assembled nanopreparation composed of MCF-7-specific phage protein and polyethylene glycol phosphatidyl ethanolamine (PEG- PE) micelles showed selective toxicity to target cancer cells rather than non-target, non- cancer cells in vitro. In vivo, the targeted phage-micelles triggered a dramatic tumor reduction and extensive necrosis as a result of improved tumor delivery of paclitaxel. The enhanced anticancer effect was also verified by an enhanced apoptosis and reduced tumor cell proliferation following the treatment with the targeted micellar paclitaxel both in vitro and in vivo. The absence of hepatotoxicity and pathological changes in tissue sections of vital organs, together with maintenance of overall health of mice following the treatment, further support its translational potential as an effective and safe chemotherapy for improved breast cancer treatment.

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Section: Methodsmentioning

confidence: 99%

Paclitaxel-Loaded PEG-PE–Based Micellar Nanopreparations Targeted with Tumor-Specific Landscape Phage Fusion Protein Enhance Apoptosis and Efficiently Reduce Tumors

Wang

Yang

Mei

et al. 2014

Molecular Cancer Therapeutics

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“…These phage particles were coupled with doxorubicin and tested in vivo. Antitumor activity was enhanced in mouse models compared to results obtained with the nontargeted formulations, and there was no detectable hepatotoxicity (186).…”

Section: Delivery Of Anticancer Drugsmentioning

confidence: 79%

Genetically Engineered Phages: a Review of Advances over the Last Decade

Pires

Cleto

Sillankorva

et al. 2016

Microbiol Mol Biol Rev

325

275

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SUMMARYSoon after their discovery in the early 20th century, bacteriophages were recognized to have great potential as antimicrobial agents, a potential that has yet to be fully realized. The nascent field of phage therapy was adversely affected by inadequately controlled trials and the discovery of antibiotics. Although the study of phages as anti-infective agents slowed, phages played an important role in the development of molecular biology. In recent years, the increase in multidrug-resistant bacteria has renewed interest in the use of phages as antimicrobial agents. With the wide array of possibilities offered by genetic engineering, these bacterial viruses are being modified to precisely control and detect bacteria and to serve as new sources of antibacterials. In applications that go beyond their antimicrobial activity, phages are also being developed as vehicles for drug delivery and vaccines, as well as for the assembly of new materials. This review highlights advances in techniques used to engineer phages for all of these purposes and discusses existing challenges and opportunities for future work.

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“…Since surface nucleolin is overexpressed in a number of tumor and tumorsurrounding cells, the promiscuity of the DMPGTVLP peptide may expend to various cancer cells and cells of tumor microenvironment, such as activated lymphocytes, angiogenic endothelial cells within the tumor vasculature and others [39]. It was shown to enhance antitumor activity of the phage-navigating nanomedicines in mice tumor models [40,41]. Promiscuous peptides of the first type have been selected in the intercellular selection scheme [32] ( Figure 2B).…”

Section: Promiscous Peptides and Proteins: Potential Navigating Sensorsmentioning

confidence: 99%

“…It was demonstrated that phage fusion proteins selectively interacting with various cellular phenotypes are ideal construction material for preparation of targeted nanomedicine platforms with increased antitumor potential toward human prostate, breast, lung and pancreatic cancer cells [40,41,81]. It was shown that the cell-binding specificity of selected phages and their proteins translates [40,90].…”

Section: The Major Coat Protein Of Landscape Phages As Antenna Of Tummentioning

confidence: 99%

Autonomous self-navigating drug-delivery vehicles: From Science Fiction to Reality

Petrenko

2017

Ther. Deliv.

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Low efficacy of targeted nanomedicines in biological experiments enforced us to challenge the traditional concept of drug targeting and suggest a paradigm of 'addressed self-navigating drug-delivery vehicles,' in which affinity selection of targeting peptides and vasculature-directed in vivo phage screening is replaced by the migration selection, which explores ability of 'promiscuous' phages and their proteins to migrate through the tumor-surrounding cellular barriers, using a 'hub and spoke' delivery strategy, and penetrate into the tumor affecting the diverse tumor cell population. The 'self-navigating' drug-delivery paradigm can be used as a theoretical and technical platform in design of a novel generation of molecular medications and imaging probes for precise and personal medicine. The first medical nanovehicle was portrayed in the science fiction movie 'Fantastic voyage'. It was a micron-size submarine navigating by a 'miniaturized' pilot along the patient's vasculature and boarded with a crew of sergeants aimed to destroy a clot in the patient's brain. Some characteristic features of the fantastic microsubmarine resemble desired vital technical characteristics of modern medical nanodevices. They include: autonomous self-navigation in the bloodstream and tissue, a means for destruction of biological barriers and tumor-surrounding threat cells, traceability for imaging of the nanovehicle location and capability to deliver a molecular cargo to the site of disease. Appearance of drug-delivery nanovehicles (nanomedicines) provoked a new impulse toward development of targeted cancer chemotherapeutics. The first generation of nanoparticle therapeutics were autonomous non-navigating vehicles [1]. They were proposed to take advantage of abnormalities in tumor vasculature for accumulation of drugs in tumor microenvironment exploring enhanced permeability and retention (EPR) effect [2,3]. In attempts to enhance their therapeutic efficacy, the second generation of nanomedicines explored the Ehrlich's 'magic bullet' concept for the nanomedicine targeting toward the vasculature and tumor cells [4]. Discovery of unique, organ-specific vasculature receptors, called 'zip codes', suggested a new approach for organ-and tumor-targeted drug delivery, harnessing the power of the in vivo phage display technique -the concept developed by Pasqualini, Ruoslahti and colleagues [4][5][6][7][8][9][10]. Since tumors were considered as a monocellular pathology, majority of anticancer therapeutics were designed to target exclusively cancer cells or cells of tumor vasculature [1]. The concept of tumor-targeted nanomedicines has been around for years, but it has been underdeveloped because mostly relied on the assumed homogeneity of tumor cells and their proximity to the defective tumor epithelium, as illustrated in Figure 1. The attempts of adapting Ehlich's ideas of direct tumor targeting have shown insignificant improvements [11]. Analysis of nanoparticle delivery data accumulated during the past decade demonstrated that only a tiny ...

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Enhanced tumor delivery and antitumor activity in vivo of liposomal doxorubicin modified with MCF-7-specific phage fusion protein

Cited by 53 publications

References 39 publications

Paclitaxel-Loaded PEG-PE–Based Micellar Nanopreparations Targeted with Tumor-Specific Landscape Phage Fusion Protein Enhance Apoptosis and Efficiently Reduce Tumors

Paclitaxel-Loaded PEG-PE–Based Micellar Nanopreparations Targeted with Tumor-Specific Landscape Phage Fusion Protein Enhance Apoptosis and Efficiently Reduce Tumors

Genetically Engineered Phages: a Review of Advances over the Last Decade

Autonomous self-navigating drug-delivery vehicles: From Science Fiction to Reality

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