title: Synergistic antitumor activity from two-stage delivery of targeted toxins and endosome-disrupting nanoparticles.
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.
authors: Department of Material Science and Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
authors: Xingfang
authors: X
authors: Su
authors: Nicole
authors: N
authors: Yang
authors: K Dane
authors: KD
authors: Wittrup
authors: Darrell J
authors: DJ
authors: Irvine
mesh_terms: D000818:Animals; D000906:Antibodies; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology; D045744:Cell Line, Tumor; D003911:Dextrans / Q000378:metabolism; D004337:Drug Carriers; D011992:Endosomes / Q000378:metabolism*; D006801:Humans; D051379:Mice; D053758:Nanoparticles; D009369:Neoplasms / Q000188:drug therapy*; D010590:Phalloidine / Q000008:administration & dosage*; D054789:Ribosome Inactivating Proteins, Type 1 / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D003911:Dextrans; D004337:Drug Carriers; D054789:Ribosome Inactivating Proteins, Type 1; D010590:Phalloidine; C025674:GEL protein, Gelonium multiflorum