Destruction of breast cancers and their metastases by lytic peptide conjugates in vitro and in vivo

Hansel, William; Enright, Frederick M.; Leuschner, Carola

doi:10.1016/j.mce.2005.12.056

Cited by 55 publications

(55 citation statements)

References 26 publications

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“…Many groups have explored the unique potential of naturally occurring and synthetic peptides for cancer chemotherapy. By covalently fusing the membrane-active peptides with receptor-targeted peptide motifs, it has been possible to achieve very specific targeting to particular tumors for highly cytotoxic peptides (6)(7)(8)(9). We now propose and demonstrate a nanoemulsion-peptide complex based on observations that certain of these membrane-active peptides would not be susceptible to traditional mechanisms of cancer resistance and that combination therapy with cytolytic peptides and standard chemotherapeutic drugs might be synergistic (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

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

Soman¹,

Baldwin²,

Hu³

et al. 2009

J. Clin. Invest.

263

277

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The in vivo application of cytolytic peptides for cancer therapeutics is hampered by toxicity, nonspecificity, and degradation. We previously developed a specific strategy to synthesize a nanoscale delivery vehicle for cytolytic peptides by incorporating the nonspecific amphipathic cytolytic peptide melittin into the outer lipid monolayer of a perfluorocarbon nanoparticle. Here, we have demonstrated that the favorable pharmacokinetics of this nanocarrier allows accumulation of melittin in murine tumors in vivo and a dramatic reduction in tumor growth without any apparent signs of toxicity. Furthermore, direct assays demonstrated that molecularly targeted nanocarriers selectively delivered melittin to multiple tumor targets, including endothelial and cancer cells, through a hemifusion mechanism. In cells, this hemifusion and transfer process did not disrupt the surface membrane but did trigger apoptosis and in animals caused regression of precancerous dysplastic lesions. Collectively, these data suggest that the ability to restrain the wide-spectrum lytic potential of a potent cytolytic peptide in a nanovehicle, combined with the flexibility of passive or active molecular targeting, represents an innovative molecular design for chemotherapy with broad-spectrum cytolytic peptides for the treatment of cancer at multiple stages.

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Section: Introductionmentioning

confidence: 99%

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

Soman¹,

Baldwin²,

Hu³

et al. 2009

J. Clin. Invest.

263

277

View full text Add to dashboard Cite

show abstract

“…Similarly, we found in 2002 that a lytic peptide-bCG conjugate was effective in reducing tumor weights in mice bearing ovarian cancer xenografts (97). In 2003 and 2007, we reported that membrane-destroying lytic peptide conjugates were also capable of destroying breast cancer cells in vitro and in vivo (93,98). Bodek et al (99) reported in 2005 that a Hecate-bCG conjugate targeted Leydig cell tumors in transgenic mice.…”

Section: Targeting Cancer Cells By Reproductive Hormones and Their Rementioning

confidence: 82%

“…The synthetic lytic peptides that we selected (Hecate, Phor14, and Phor21) were each conjugated to segments of the b chain of CG or FSH or to LHRH. These conjugates (Hecate-bCG, Phor14-bCG, Phor21-bCG, LHRH-Hecate, and LHRH-Phor21) are described in greater detail by Hansel et al (93).…”

Section: Targeting Cancer Cells By Reproductive Hormones and Their Rementioning

confidence: 99%

After 65 Years, Research Is Still Fun

Hansel

2013

Annu. Rev. Anim. Biosci.

Self Cite

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In 1946, at the end of World War II, I entered graduate school at Cornell University, where I remained for 44 years. During that time, my laboratory produced more than 300 publications in the field of reproductive biology, including studies on nutrition and reproduction, the role of the hypothalamus in pituitary gonadotropin release, corpus luteum formation and function, hormone assays, and estrous cycle synchronization. At age seventy,

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“…LPs can be included in LILs as active molecules that promote cytotoxic effects. LPs have already been used covalently linked to hormone segments in order to increase their efficacy and selectivity on several types of cancer cells (Gawronska, Leuschner et al, 2002;Hansel, Enright et al, 2006). Nevertheless, a therapy based on this approach might be valid only for those tumors expressing hormone receptors, such as prostate or breast cancers.…”

Section: The Lytic Peptidesmentioning

confidence: 99%