In vivo tumor imaging using a novel RNAi-based detection mechanism
Abstract
A new concept of tumor imaging is introduced using a siRNA-based probe that is capable of amplifying a specific endogenous fluorescence emission in cancerous tissue. In previous studies, we demonstrated a significant downregulation of Ferrochelatase (FECH) mRNA-expression in colorectal carcinomas leading to the accumulation of protoporphyrin IX (PpIX), a fluorescent metabolite of the heme synthesis. In this article, we report on first in vivo experiments in xenografted nude mice using folate-coupled liposomes or dendritic polyglycerolamine nanoparticles carrying ferrochelatase-siRNA to enhance PpIX-derived fluorescence in the tumor tissue. Tiny tumor foci could be monitored by the emission of PpIX fluorescence in vivo. Due to the omnipresence of the heme synthesis pathway, targeted application of ferrochelatase-siRNA may provide a general means for molecular imaging. From the clinical editor A new concept of tumor imaging is presented in this paper using a siRNA-based probe detecting protoporphyrin IX (PpIX), a fluorescent metabolite of the heme synthesis previously demonstrated to accumulate in cancer tissue.
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Genetic silencing of FECH significantly increases ALA-PpIX fluorescence in multiple cell lines and even in an animal study.
“Although genetic silencing of FECH significantly increases ALA-PpIX fluorescence in multiple cell lines [108,109,110,111] and even in an animal study [112], pharmacological inhibition of FECH with enzymatic inhibitors for the enhancement of PpIX has not been well studied.”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [112]
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References 13 · Cited by 21
- Authors
- Wan, K., Ebert, B., Voigt, J., Wang, Q., Dai, Y., Haag, R., & Kemmner, W.
- Affiliations
- Charité – Universitätsmedizin Berlin (DE)
- Physikalisch-Technische Bundesanstalt (DE)
- Freie Universität Berlin (DE)
- Corresponding author
- Kemmner, Wolfgang
- Venue
- Nanomedicine: Nanotechnology, Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2012-05
- Volume
- 8
- Issue
- 4
- Pages
- 393-398
- ISSN
- 1549-9634 (ISSN-L)
- OpenAlex
- W2028733665
- Cited by
- 21
- References
- 13
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 1 · 2021: 5 · 2020: 1 · 2019: 1 · 2016: 3 · 2015: 1 · 2014: 3 · 2013: 3 · 2012: 1
- FWCI
- 1.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nanomedicine Nanotechnology Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Keywords
- tumor imaging, ferrochelatase, protoporphyrin IX, heme biosynthesis, RNA interference, fluorescence imaging, colorectal cancer, nude mouse xenograft, molecular imaging
- MeSH terms
- Animals, Female, Ferrochelatase, Fluorescence, Humans, Mice, Nude, Neoplasm Proteins, Neoplasm Transplantation, Protoporphyrins, RNA, Messenger, RNA, Neoplasm, Transplantation, Heterologous, Colorectal Neoplasms, RNA Probes, Mice, Nanoparticles
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