Minicircles for a two-step blood biomarker and PET imaging early cancer detection strategy.

Autor: Robinson ER; Department of Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University School of Medicine, Stanford, CA 94305, USA., Gowrishankar G; Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University School of Medicine, Stanford, CA 94305, USA., D'Souza AL; Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University School of Medicine, Stanford, CA 94305, USA., Kheirolomoom A; Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University School of Medicine, Stanford, CA 94305, USA., Haywood T; Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University School of Medicine, Stanford, CA 94305, USA., Hori SS; Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University School of Medicine, Stanford, CA 94305, USA; Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Palo Alto, CA 94304, USA., Chuang HY; Department of Biomedical Imaging and Radiological Sciences, National Yang Ming University, Taipei, Taiwan., Zeng Y; Department of Materials Science and Engineering, Stanford University, Stanford, CA 94305, USA., Tumbale SK; Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University School of Medicine, Stanford, CA 94305, USA., Aalipour A; Department of Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University School of Medicine, Stanford, CA 94305, USA., Beinat C; Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University School of Medicine, Stanford, CA 94305, USA., Alam IS; Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University School of Medicine, Stanford, CA 94305, USA., Sathirachinda A; Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University School of Medicine, Stanford, CA 94305, USA., Kanada M; Institute for Quantitative Health Science and Engineering (IQ), Michigan State University, East Lansing, MI 48824., USA., Paulmurugan R; Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University School of Medicine, Stanford, CA 94305, USA; Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Palo Alto, CA 94304, USA., Ferrara KW; Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University School of Medicine, Stanford, CA 94305, USA; Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Palo Alto, CA 94304, USA. Electronic address: kwferrar@stanford.edu., Gambhir SS; Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University School of Medicine, Stanford, CA 94305, USA; Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
Jazyk: angličtina
Zdroj: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2021 Jul 10; Vol. 335, pp. 281-289. Date of Electronic Publication: 2021 May 21.
DOI: 10.1016/j.jconrel.2021.05.026
Abstrakt: Early cancer detection can dramatically increase treatment options and survival rates for patients, yet detection of early-stage tumors remains difficult. Here, we demonstrate a two-step strategy to detect and locate cancerous lesions by delivering tumor-activatable minicircle (MC) plasmids encoding a combination of blood-based and imaging reporter genes to tumor cells. We genetically engineered the MCs, under the control of the pan-tumor-specific Survivin promoter, to encode: 1) Gaussia Luciferase (GLuc), a secreted biomarker that can be easily assayed in blood samples; and 2) Herpes Simplex Virus Type 1 Thymidine Kinase mutant (HSV-1 sr39TK), a PET reporter gene that can be used for highly sensitive and quantitative imaging of the tumor location. We evaluated two methods of MC delivery, complexing the MCs with the chemical transfection reagent jetPEI or encapsulating the MCs in extracellular vesicles (EVs) derived from a human cervical cancer HeLa cell line. MCs delivered by EVs or jetPEI yielded significant expression of the reporter genes in cell culture versus MCs delivered without a transfection reagent. Secreted GLuc correlated with HSV-1 sr39TK expression with R 2  = 0.9676. MC complexation with jetPEI delivered a larger mass of MC for enhanced transfection, which was crucial for in vivo animal studies, where delivery of MCs via jetPEI resulted in GLuc and HSV-1 sr39TK expression at significantly higher levels than controls. To the best of our knowledge, this is the first report of the PET reporter gene HSV-1 sr39TK delivered via a tumor-activatable MC to tumor cells for an early cancer detection strategy. This work explores solutions to endogenous blood-based biomarker and molecular imaging limitations of early cancer detection strategies and elucidates the delivery capabilities and limitations of EVs.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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