有哪些信誉好的足球投注网站multi-modality therapeutics with potent anti-tumor effects photochemical internalization enhances delivery of the fusion toxin scfvmelrgel多模和强有力的抗肿瘤效果光化学疗法内化增强融合毒素scfvmelrgel的交付.pdfVIP
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multi-modality therapeutics with potent anti-tumor effects photochemical internalization enhances delivery of the fusion toxin scfvmelrgel多模和强有力的抗肿瘤效果光化学疗法内化增强融合毒素scfvmelrgel的交付
Multi-Modality Therapeutics with Potent Anti-Tumor Effects: Photochemical Internalization Enhances Delivery of the Fusion Toxin scFvMEL/rGel ˚ 1 2 2 2 1 Pal K. Selbo *, Michael G. Rosenblum , Lawrence H. Cheung , Wendy Zhang , Kristian Berg 1 Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway, 2 Immunopharmacology and Targeted Therapy Laboratory, Department of Experimental Therapeutics, M. D. Anderson Cancer Center, Houston, Texas, United States of America Abstract Background: There is a need for drug delivery systems (DDS) that can enhance cytosolic delivery of anti-cancer drugs trapped in the endo-lysosomal compartments. Exposure of cells to specific photosensitizers followed by light exposure (photochemical internalization, PCI) results in transfer of agents from the endocytic compartment into the cytosol. Methodology and Principal Findings: The recombinant single-chain fusion construct scFvMEL/rGel is composed of an antibody targeting the progenitor marker HMW-MAA/NG2/MGP/gp240 and the highly effective toxin gelonin (rGel). Here we demonstrate enhanced tumor cell selectivity, cytosolic delivery and anti-tumor activity by applying PCI of scFvMEL/rGel. PCI performed by light activation of cells co-incubated with scFvMEL/rGel and the endo-lysosomal targeting photosensitizers AlPcS2a or TPPS2a resulted in enhanced cytotoxic effects against antigen-positive cell lines, while no differences in cytotoxicity between the scFvMEL/rGel and rGel were observed in antigen-negative cells. Mice bearing well- developed melanoma (A-375) xenografts (50–100 mm3) were treated with
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