pHLIP®-mediated delivery of PEGylated liposomes to cancer cells

Yao, Lan; Daniels, Jennifer; Wijesinghe, Dayanjali; Andreev, Oleg A.; Reshetnyak, Yana K.

doi:10.1016/j.jconrel.2013.01.037

Cited by 78 publications

(91 citation statements)

References 53 publications

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“…We also observed some staining of internal organelles and nuclei membranes. Targeting of mitochondria and nuclear membranes was observed in experiments with pHLIP-coated liposomes containing lipids conjugated with fluorescent dyes and gold nanoparticles (26).…”

Section: Resultsmentioning

confidence: 99%

“…The pH-sensitive targeting agents we are developing are based on the action of a family of pHLIPs (pH Low-Insertion Peptides), which can "sense" acidity at the surface of cancer cells and deliver diagnostic and therapeutic molecules to tumors of different origins (20)(21)(22)(23)(24)(25). It was shown that pHLIP can promote fusion of liposomes with cancer cells and cellular delivery of various payloads (26,27), including small gold nanoparticles (26). Recently, pHLIP was successfully used for the targeting of various nanoparticles to tumors and other acidic diseased tissue (28)(29)(30)(31).…”

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confidence: 99%

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Enhancement of radiation effect on cancer cells by gold-pHLIP

Antosh

Wijesinghe

Shrestha

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Previous research has shown that gold nanoparticles can increase the effectiveness of radiation on cancer cells. Improved radiation effectiveness would allow lower radiation doses given to patients, reducing adverse effects; alternatively, it would provide more cancer killing at current radiation doses. Damage from radiation and gold nanoparticles depends in part on the Auger effect, which is very localized; thus, it is important to place the gold nanoparticles on or in the cancer cells. In this work, we use the pH-sensitive, tumor-targeting agent, pH Low-Insertion Peptide (pHLIP), to tether 1.4-nm gold nanoparticles to cancer cells. We find that the conjugation of pHLIP to gold nanoparticles increases gold uptake in cells compared with gold nanoparticles without pHLIP, with the nanoparticles distributed mostly on the cellular membranes. We further find that gold nanoparticles conjugated to pHLIP produce a statistically significant decrease in cell survival with radiation compared with cells without gold nanoparticles and cells with gold alone. In the context of our previous findings demonstrating efficient pHLIP-mediated delivery of gold nanoparticles to tumors, the obtained results serve as a foundation for further preclinical evaluation of dose enhancement.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Enhancement of radiation effect on cancer cells by gold-pHLIP

Antosh

Wijesinghe

Shrestha

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…It also has been used to target various nanoparticles (41,42) (43) and liposomes (39,44) to acidic tissue. Studies differ as to whether the actual pH was determined by 31 P magnetic resonance spectroscopy (MRS) (32,34,38) or other methods (45).…”

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confidence: 99%

The pH low insertion peptide pHLIP Variant 3 as a novel marker of acidic malignant lesions

Tapmeier

Moshnikova

Beech

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Current strategies for early detection of breast and other cancers are limited in part because some lesions identified as potentially malignant do not develop into aggressive tumors. Acid pH has been suggested as a key characteristic of aggressive tumors that might distinguish aggressive lesions from more indolent pathology. We therefore investigated the novel class of molecules, pH low insertion peptides (pHLIPs), as markers of low pH in tumor allografts and of malignant lesions in a mouse model of spontaneous breast cancer, BALB/neu-T. pHLIP Variant 3 (Var3) conjugated with fluorescent Alexa546 was shown to insert into tumor spheroids in a sequence-specific manner. Its signal reflected pH in murine tumors. It was induced by carbonic anhydrase IX (CAIX) overexpression and inhibited by acetazolamide (AZA) administration. By using 31 P magnetic resonance spectroscopy (MRS), we demonstrated that pHLIP Var3 was retained in tumors of pH equal to or less than 6.7 but not in tissues of higher pH. In BALB/neu-T mice at different stages of the disease, the fluorescent signal from pHLIP Var3 marked cancerous lesions with a very low false-positive rate. However, only ∼60% of the smallest lesions retained a pHLIP Var3 signal, suggesting heterogeneity in pH. Taken together, these results show that pHLIP can identify regions of lower pH, allowing for its development as a theranostic tool for clinical applications.

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“…(4) Cancer therapy: Success of Doxil promotes the research and development of liposomes carrying anticancer drug. Further understanding of how actively targeted liposomes behave in vivo and subsequent optimization of liposome design could translate into successful applications of targeted liposomes in the clinic, providing the potential for substantial breakthroughs in cancer therapeutics (Qhattal and Liu 2011;Gray et al 2013;Deshpande et al 2013;Yao et al 2013). Taken together, nanotechnology, drug delivery, siRNA and cancer therapy are trends of liposome.…”

Section: Research Trendsmentioning

confidence: 99%

Global liposome research in the period of 1995–2014: a bibliometric analysis

Zhou

Zhao

2015

Scientometrics

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In this study, we aim to evaluate the global scientific output of liposome research, and try to find an approach to quantitatively and qualitatively assess the current global research on liposome. Data were based on the science citation index expanded database, from the Institute of Scientific Information Web of Science database. Bibliometric method was used to analyze publication outputs, journals, countries/territories, institutions, authors, research areas, research hotspots and trends. Globally, there were 37,327 publications referring to liposome during 1995-2014. Liposome research experienced notable growth in the past two decades. The International Journal of Pharmaceutics published the largest number of liposome-related publications in the surveyed period. Major author clusters and research regions are located in the USA, Western Europe, and Asia. The USA was a leading contributor to liposome research with the largest number of publications. The Osaka Univ (Japan), Kyoto Univ (Japan), and Univ Texas (USA) were the three institutions with the largest number of liposome-related publications. Van Rooijen N (Netherlands) was a leading contributor to liposome research with the largest number of publications. The chemistry accounts for the largest number of publications in the research area of liposomes. A keywords analysis revealed that gene, drug delivery, cell and cancer were the research hotspots in the study period. The nanotechnology, drug delivery, small interfering RNA and cancer therapy received dramatically increased attention during the analyzed period, possibly signaling future research trends. Bibliometric method could quantitatively characterize the development of global liposome research.

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pHLIP®-mediated delivery of PEGylated liposomes to cancer cells

Cited by 78 publications

References 53 publications

Enhancement of radiation effect on cancer cells by gold-pHLIP

Enhancement of radiation effect on cancer cells by gold-pHLIP

The pH low insertion peptide pHLIP Variant 3 as a novel marker of acidic malignant lesions

Global liposome research in the period of 1995–2014: a bibliometric analysis

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