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- W4361949103 abstract "<div>Abstract<p><b>Purpose:</b> Saposin C is a multifunctional protein known to activate lysosomal enzymes and induce membrane fusion in an acidic environment. Excessive accumulation of lipid-coupled saposin C in lysosomes is cytotoxic. Because neoplasms generate an acidic microenvironment, caused by leakage of lysosomal enzymes and hypoxia, we hypothesized that saposin C may be an effective anticancer agent. We investigated the antitumor efficacy and systemic biodistribution of nanovesicles comprised of saposin C coupled with dioleoylphosphatidylserine in preclinical cancer models.</p><p><b>Experimental Design:</b> Neuroblastoma, malignant peripheral nerve sheath tumor and, breast cancer cells were treated with saposin C–dioleoylphosphatidylserine nanovesicles and assessed for cell viability, ceramide elevation, caspase activation, and apoptosis. Fluorescently labeled saposin C–dioleoylphosphatidylserine was i.v. injected to determine <i>in vivo</i> tumor-targeting specificity. Antitumor activity and toxicity profile of saposin C–dioleoylphosphatidylserine were evaluated in xenograft models.</p><p><b>Results:</b> Saposin C–dioleoylphosphatidylserine nanovesicles, with a mean diameter of ∼190 nm, showed specific tumor-targeting activity shown through <i>in vivo</i> imaging. Following i.v. administration, saposin C–dioleoylphosphatidylserine nanovesicles preferentially accumulated in tumor vessels and cells in tumor-bearing mice. Saposin C–dioleoylphosphatidylserine induced apoptosis in multiple cancer cell types while sparing normal cells and tissues. The mechanism of saposin C–dioleoylphosphatidylserine induction of apoptosis was determined to be in part through elevation of intracellular ceramides, followed by caspase activation. In <i>in vivo</i> models, saposin C–dioleoylphosphatidylserine nanovesicles significantly inhibited growth of preclinical xenografts of neuroblastoma and malignant peripheral nerve sheath tumor. I.v. dosing of saposin C–dioleoylphosphatidylserine showed no toxic effects in nontumor tissues.</p><p><b>Conclusions:</b> Saposin C–dioleoylphosphatidylserine nanovesicles offer promise as a novel, nontoxic, cancer-targeted, antitumor agent for treating a broad range of cancers. (Clin Cancer Res 2009;15(18):5840–51)</p></div>" @default.
- W4361949103 created "2023-04-05" @default.
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- W4361949103 date "2023-03-31" @default.
- W4361949103 modified "2023-10-14" @default.
- W4361949103 title "Data from Cancer-Selective Targeting and Cytotoxicity by Liposomal-Coupled Lysosomal Saposin C Protein" @default.
- W4361949103 doi "https://doi.org/10.1158/1078-0432.c.6517798.v1" @default.
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