Explore the vast range of titles available.

Advances in precision molecular imaging promise to transform our ability to detect, diagnose and treat disease. Here, we describe the engineering and validation of a new cystine knot peptide (knottin) that selectively recognizes human integrin αvβ 6 with single-digit nanomolar affinity. We solve its 3D structure by NMR and x-ray crystallography and validate leads with 3 different radiolabels in pre-clinical models of cancer. We evaluate the lead tracer’s safety, biodistribution and pharmacokinetics in healthy human volunteers, and show its ability to detect multiple cancers (pancreatic, cervical and lung) in patients at two study locations. Additionally, we demonstrate that the knottin PET tracers can also detect fibrotic lung disease in idiopathic pulmonary fibrosis patients. Our results indicate that these cystine knot PET tracers may have potential utility in multiple disease states that are associated with upregulation of integrin α v β 6 . Knottin is a cystine knot peptide. Here, the authors develop a knottin-based tracer for positron emission tomography and demonstrate its ability to detect cancer and idiopathic pulmonary fibrosis through selective binding to integrin αvβ 6 .

Aim: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype. Since no targeted therapy is available, gene-directed enzyme prodrug therapy (GDEPT) could be an attractive strategy for treating TNBC. Materials & methods: Polyethylene glycol (PEG)ylated-poly(lactic-co-glycolic acid)/polyethyleneimine nanoparticles (PLGA/PEI NPs) were synthesized and complexed with TK–NTR fusion gene. Ultrasound (US) and microbubble (MB) mediated sonoporation was used for efficient delivery of the TK–NTR–DNA–NP complex to TNBC tumor in vivo for cancer therapy. Therapeutic effect was evaluated by treating TNBC cells in vitro and tumor xenograft in vivo by using prodrugs ganciclovir (GCV) and CB1954. Results: TNBC cells treated with GCV/CB1954 prodrugs after transfection of TK–NTR–DNA by PEGylated-PLGA/PEI NP resulted in high apoptotic-index. US–MB image-guided delivery of TK–NTR–DNA–NP complex displayed significant expression level of TK–NTR protein and showed tumor reduction when treated with GCV/CB1954 prodrugs in TNBC xenograft in vivo. Conclusion: US–MB image-guided delivery of TK–NTR gene by PEGylated-PLGA/PEI NPs could be a potential prodrug therapy for TNBC in the clinic.

This study explores the use of hydrophilic poly(ethylene glycol)-conjugated poly(lactic-co-glycolic acid) nanoparticles (PLGA-PEG-NPs) as delivery system to improve the antitumor effect of antiobesity drug orlistat for triple-negative breast cancer (TNBC) therapy by improving its bioavailability. PLGA-PEG-NPs were synthesized by emulsion-diffusion-evaporation method, and the experiments were conducted in MDA-MB-231 and SKBr3 TNBC and normal breast fibroblast cells. Delivery of orlistat via PLGA-PEG-NPs reduced its IC compared with free orlistat. Combined treatment of orlistat-loaded NPs and doxorubicin or antisense-miR-21-loaded NPs significantly enhanced apoptotic effect compared with independent doxorubicin, anti-miR-21-loaded NPs, orlistat-loaded NPs or free orlistat treatments. We demonstrate that orlistat in combination with antisense-miR-21 or current chemotherapy holds great promise as a novel and versatile treatment agent for TNBC.

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype. Since no targeted therapy is available, gene-directed enzyme prodrug therapy (GDEPT) could be an attractive strategy for treating TNBC. Polyethylene glycol (PEG)ylated-poly(lactic-co-glycolic acid)/polyethyleneimine nanoparticles (PLGA/PEI NPs) were synthesized and complexed with fusion gene. Ultrasound (US) and microbubble (MB) mediated sonoporation was used for efficient delivery of the -DNA-NP complex to TNBC tumor for cancer therapy. Therapeutic effect was evaluated by treating TNBC cells and tumor xenograft by using prodrugs ganciclovir (GCV) and CB1954. TNBC cells treated with GCV/CB1954 prodrugs after transfection of -DNA by PEGylated-PLGA/PEI NP resulted in high apoptotic-index. US-MB image-guided delivery of -DNA-NP complex displayed significant expression level of TK-NTR protein and showed tumor reduction when treated with GCV/CB1954 prodrugs in TNBC xenograft . US-MB image-guided delivery of gene by PEGylated-PLGA/PEI NPs could be a potential prodrug therapy for TNBC in the clinic.

Abstract Advances in precision molecular imaging promise to transform our ability to detect, diagnose and treat disease. Here, we describe the engineering and validation of a new cystine knot peptide (knottin) that selectively recognizes human integrin αvβ 6 with single-digit nanomolar affinity. We solve its 3D structure by NMR and x-ray crystallography and validate leads with 3 different radiolabels in pre-clinical models of cancer. We evaluate the lead tracer’s safety, biodistribution and pharmacokinetics in healthy human volunteers, and show its ability to detect multiple cancers (pancreatic, cervical and lung) in patients at two study locations. Additionally, we demonstrate that the knottin PET tracers can also detect fibrotic lung disease in idiopathic pulmonary fibrosis patients. Our results indicate that these cystine knot PET tracers may have potential utility in multiple disease states that are associated with upregulation of integrin α v β 6 .

Advances in precision molecular imaging promise to transform our ability to detect, diagnose and treat disease. Here, we describe the engineering and validation of a new cystine knot peptide (knottin) that selectively recognizes human integrin αvβ with single-digit nanomolar affinity. We solve its 3D structure by NMR and x-ray crystallography and validate leads with 3 different radiolabels in pre-clinical models of cancer. We evaluate the lead tracer's safety, biodistribution and pharmacokinetics in healthy human volunteers, and show its ability to detect multiple cancers (pancreatic, cervical and lung) in patients at two study locations. Additionally, we demonstrate that the knottin PET tracers can also detect fibrotic lung disease in idiopathic pulmonary fibrosis patients. Our results indicate that these cystine knot PET tracers may have potential utility in multiple disease states that are associated with upregulation of integrin α β .