title: Quantum dot-conjugated anti-GRP78 scFv inhibits cancer growth in mice.
abstract: Semiconductor quantum dots (Qdots) have recently been shown to offer significant advantages over conventional fluorescent probes to image and study biological processes. The stability and low toxicity of QDs are well suited for biological applications. Despite this, the potential of Qdots remains limited owing to the inefficiency of existing delivery methods. By conjugating Qdots with small antibody fragments targeting membrane-bound proteins, such as GRP78, we demonstrate here that the Quantum dot- Anti-GRP78 scFv (Qdot-GRP78) retains its immunospecificity and its distribution can be monitored by visualization of multi-color fluorescence imaging both in vitro and in vivo. Moreover we demonstrate here for the first time that Qdot-GRP78 scFv bioconjugates can be efficiently internalized by cancer cells, thus upregulate phophosphate-AKT-ser473 and possess biological anti-tumour activity as shown by inhibition of breast cancer growth in a xenograft model. This suggests that nanocarrier-conjugated scFvs can be used as a therapeutic antibody for cancer treatment.
authors.affiliation: Department of Molecular Biology and Biotechnology, The Krebs Institute, The University of Sheffield, S10 2TN, UK. weiming.xu@sheffield.ac.uk
authors.forename: Weiming
authors.initials: W
authors.lastname: Xu
authors.forename: Lizhi
authors.initials: L
authors.lastname: Liu
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Brown
authors.forename: Sven
authors.initials: S
authors.lastname: Christian
authors.forename: David
authors.initials: D
authors.lastname: Hornby
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D006360:Heat-Shock Proteins / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D011471:Prostatic Neoplasms; D045663:Quantum Dots; D057127:Single-Chain Antibodies / Q000494:pharmacology / Q000627:therapeutic use*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D000922:Immunotoxins; D057127:Single-Chain Antibodies