Abstract
Plant-derived Type I toxins are candidate anticancer therapeutics requiring cytosolic delivery into tumor cells. We tested a concept for two-stage delivery, whereby tumor cells precoated with an antibody-targeted gelonin toxin were killed by exposure to endosome-disrupting polymer nanoparticles. Co-internalization of particles and tumor cell-bound gelonin led to cytosolic delivery and >50-fold enhancement of toxin efficacy. This approach allows the extreme potency of gelonin to be focused on tumors with significantly reduced potential for off-target toxicity.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Antibodies
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Antineoplastic Agents / administration & dosage*
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Antineoplastic Agents / metabolism
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents, Phytogenic / administration & dosage*
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Antineoplastic Agents, Phytogenic / pharmacology
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Cell Line, Tumor
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Dextrans / metabolism
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Drug Carriers*
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Endosomes / metabolism*
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Humans
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Mice
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Nanoparticles
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Neoplasms / drug therapy*
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Phalloidine / administration & dosage*
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Ribosome Inactivating Proteins, Type 1 / administration & dosage*
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Ribosome Inactivating Proteins, Type 1 / chemistry
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Ribosome Inactivating Proteins, Type 1 / pharmacology
Substances
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Antibodies
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Antineoplastic Agents
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Antineoplastic Agents, Phytogenic
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Dextrans
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Drug Carriers
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Ribosome Inactivating Proteins, Type 1
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Phalloidine
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GEL protein, Gelonium multiflorum