Molecularly targeted nanocarriers deliver the cytolytic peptide melittin specifically to tumor cells in mice, reducing tumor growth

Soman, Neeleesh R; Baldwin, Steven L.; Hu, Grace; Marsh, Jon N.; Lanza, Gregory M.; Heuser, John E.; Arbeit, Jeffrey M.; Wickline, Samuel A.; Schlesinger, Paul H.

doi:10.1172/jci38842

Cited by 265 publications

(299 citation statements)

References 68 publications

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“…We coupled small interfering RNA (siRNA) to perfluocarbon-nanoparticles (PFC-NPs) and nebulized the mixture for aerosol application. PFC-NPs have been used in a variety of biomedical applications, including delivery of RNAi to tumor cells (22,23), but had never before been nebulized.…”

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confidence: 99%

RNA interference knockdown of DNA methyl-transferase 3 affects gene alternative splicing in the honey bee

Li-Byarlay

Stroud

et al. 2013

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

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225

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Studies of DNA methylation from fungi, plants, and animals indicate that gene body methylation is ancient and highly conserved in eukaryotic genomes, but its role has not been clearly defined. It has been postulated that regulation of alternative splicing of transcripts was an original function of DNA methylation, but a direct experimental test of the effect of methylation on alternative slicing at the whole genome level has never been performed. To do this, we developed a unique method to administer RNA interference (RNAi) in a high-throughput and noninvasive manner and then used it to knock down the expression of DNA methyltransferase 3 (dnmt3), which is required for de novo DNA methylation. We chose the honey bee (Apis mellifera) for this test because it has recently emerged as an important model organism for studying the effects of DNA methylation on development and social behavior, and DNA methylation in honey bees is predominantly on gene bodies. Here we show that dnmt3 RNAi decreased global genomic methylation level as expected and in addition caused widespread and diverse changes in alternative splicing in fat tissue. Four different types of splicing events were affected by dnmt3 gene knockdown, and change in two types, exon skipping and intron retention, was directly related to decreased methylation. These results demonstrate that one function of gene body DNA methylation is to regulate alternative splicing.epigenetics | gene regulation | gene silencing | insect

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mentioning

confidence: 99%

RNA interference knockdown of DNA methyl-transferase 3 affects gene alternative splicing in the honey bee

Li-Byarlay

Stroud

et al. 2013

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

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225

221

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“…Even the badly toxic and unstable pharmacon, such as the peptide melittin, was successful targeted to murine tumors due to be attached to PFC nanoparticles [111,112]. As a result, the dramatically regressive tumors without noticeable systemic toxicity were observed.…”

Section: The Mechanism Of Pfc Nanoparticles For Drug Deliverymentioning

confidence: 99%

Phase-transition Perfluorocarbon Nanoparticles for Ultrasound Molecular Imaging and Therapy

Xu¹,

Cao²,

Xu³

et al. 2015

Nano BioMed ENG

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Recently, the advances in perfluorocarbon nanoparticles have been introduced to expand the diagnostic and therapeutic capability of ultrasound molecular imaging, a non-invasive diagnostic imaging, which passed from robust anatomical presentation to detection of physiological processes and recognition of specific tissue epitopes at the cellular level. The good properties of perfluorocarbon nanoparticles, such as nontoxicity, small size, phase-shift capability, etc., have been resulted in tremendous potential prospects in clinical application. Herein, this review focuses on the mechanisms of perfluorocarbon nanoparticles in terms of phase transition and ultrasonic theranostic. And the potential applications of perfluorocarbon nanoparticles in ultrasound medicine are also discussed.

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“…Secreted phospholipases A2 from BV have potent anti-HIV activities (19). A nanoscale delivery vehicle for cytolytic peptides was demonstrated by incorporating the non-specific amphipathic cytolytic peptide melittin into the outer lipid monolayer of a perfluorocarbon nanoparticle (20). The nanovehicles were delivered significant payloads of melittin i.v.…”

Section: Introductionmentioning

confidence: 99%

Honeybee venom possesses anticancer and antiviral effects by differential inhibition of HPV E6 and E7 expression on cervical cancer cell line

et al. 2015

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Abstract. Bee venom (BV) therapy is a type of alternative medical treatment used to treat various diseases in oriental medicine. The mechanisms underlying the effects of BV remain poorly understood. In the present study, we evaluated the antiviral effect of BV on cervical carcinoma cell lines (CaSki, HeLa, C33A and TC-1). BV treatments resulted in a more significant suppression of cell growth in HPV 16-infected cells (CaSki) and a lesser suppression in HPV 18-infected cells (HeLa). However, less suppression was observed in HPV-negative C33A cells. In 10 µg/ml BV-treated CaSki cells, the mRNA expression and protein levels of HPV16 E6 and E7 were significantly decreased by BV, while HPV18 E6 and E7 mRNA expression levels were not significantly altered by 10 µg/ml BV-treated HeLa cells. The antitumor effects of BV were in accordance with in vitro data, in restricting tumor growth in vivo and were much more effective on the suppression of tumor growth. Furthermore, the mRNA and protein expression levels of HPV16 E6 and E7 were decreased by BV in TC-1 tumors. These findings demonstrated the antiviral effects of BV in HPV-infected cervical cancer cells and the anticancer effects of BV in HPV16 E6/E7-expressed TC-1 tumors. Collectively, BV plays a differential role in suppressing HPV16-infected cells (CaSki cells) and HPV18-infected cells (HeLa cells) by the downregulation of E6/E7 protein of HPV16/18.

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Molecularly targeted nanocarriers deliver the cytolytic peptide melittin specifically to tumor cells in mice, reducing tumor growth

Cited by 265 publications

References 68 publications

RNA interference knockdown of DNA methyl-transferase 3 affects gene alternative splicing in the honey bee

RNA interference knockdown of DNA methyl-transferase 3 affects gene alternative splicing in the honey bee

Phase-transition Perfluorocarbon Nanoparticles for Ultrasound Molecular Imaging and Therapy

Honeybee venom possesses anticancer and antiviral effects by differential inhibition of HPV E6 and E7 expression on cervical cancer cell line

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