ArticleEuropean journal of nuclear medicine and molecular imaging2007
123I-labeled HIV-1 tat peptide radioimmunoconjugates are imported into the nucleus of human breast cancer cells and functionally interact in vitro and in vivo with the cyclin-dependent kinase inhibitor, p21(WAF-1/Cip-1).
Article in European journal of nuclear medicine and molecular imaging, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 52 citations in OpenAlex.
- Molecular Imaging of p53 in Mouse Models of Cancer Using a Radiolabeled Antibody TAT Conjugate with SPECT.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2024Article
- Radioimmunotheragnosis in Cancer Research.Cancers · 2024Review
- Application of Cell Penetrating Peptides as a Promising Drug Carrier to Combat Viral Infections.Molecular biotechnology · 2023Review
- A Model System to Explore the Detection Limits of Antibody-Based Immuno-SPECT Imaging of Exclusively Intranuclear Epitopes.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2021Article
- Demonstration of intracellular trafficking, cytosolic bioavailability, and target manipulation of an antibody delivery platform.Nanomedicine : nanotechnology, biology, and medicine · 2021Article
- A Novel Proteomic Method Reveals NLS Tagging of T-DM1 Contravenes Classical Nuclear Transport in a Model of HER2-Positive Breast Cancer.Molecular therapy. Methods & clinical development · 2020Article
- Antibody Delivery for Intracellular Targets: Emergent Therapeutic Potential.Bioconjugate chemistry · 2019Review
- Targeted Intracellular Delivery of Antibodies: The State of the Art.Frontiers in pharmacology · 2018Review
- Article
- Imaging DNA damage in vivo using gammaH2AX-targeted immunoconjugates.Cancer research · 2011Article
- Targeting the Tumour: Cell Penetrating Peptides for Molecular Imaging and Radiotherapy.Pharmaceuticals (Basel, Switzerland) · 2010Review
- Auger processes in the 21st century.International journal of radiation biology · 2008Review
- Creation of a bi-directional protein transduction system for suppression of HIV-1 expression by p27SJ.Antiviral research · 2008Article
- Cell-penetrating peptides and antibodies: a new direction for optimizing radioimmunotherapy.European journal of nuclear medicine and molecular imaging · 2007Article
- The taming of the cell penetrating domain of the HIV Tat: myths and realities.Journal of controlled release : official journal of the Controlled Release Society · 2007Review
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6 authors at 2 institutions in 1 country.
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Abstract
purposeTo evaluate the internalization and nuclear translocation of (123)I-tat-peptide radioimmunoconjugates in MDA-MB-468 breast cancer cells and their ability to interact with the cyclin-dependent kinase inhibitor, p21(WAF-1/Cip-1).
methodsPeptides [GRKKRRQRRRPPQGYGC] harboring the nuclear-localizing sequence from HIV tat domain were conjugated to anti-p21(WAF-1/Cip-1) antibodies. Immunoreactivity was assessed by Western blot using lysate from MDA-MB-468 cells exposed to EGF to induce p21(WAF-1/Cip-1). Internalization and nuclear translocation were measured. The ability of tat-anti-p21(WAF-1/Cip-1) to block G(1)-S phase arrest in MDA-MB-468 cells caused by EGF-induced p21(WAF-1/Cip-1) was evaluated. Tumor and normal tissue uptake were determined at 48 h p.i. in athymic mice implanted s.c. with MDA-MB-468 xenografts injected intratumorally with EGF.
resultsThere was 13.4+/-0.2% of radioactivity internalized by MDA-MB-468 cells incubated with (123)I-tat-anti-p21(WAF-1/Cip-1) and 34.6+/-3.1% imported into the nucleus. Tat-anti-p21(WAF-1/Cip-1)(8 muM) decreased the proportion of EGF-treated cells in G(1) phase from 81.9+/-0.7% to 46.1+/-0.7% (p<0.001), almost restoring the G(1) phase fraction to that of unexposed cells (25.8+/-0.2%). Non-specific tat-mouse IgG did not block EGF-induced G(1)-S phase arrest. Tumor uptake of radioactivity was higher in mice injected with EGF to induce p21(WAF-1/Cip-1) than in mice not receiving EGF (3.1+/-0.4% versus 1.8+/-0.2% ID/g; p=0.04). Western blot analysis of tumors revealed a threefold increase in the p21(WAF-1/Cip-1)/beta-actin ratio.
conclusionWe conclude that intracellular and nuclear epitopes in cancer cells can be functionally targeted with tat-radioimmunoconjugates to exploit many more epitopes for imaging and radiotherapeutic applications than have previously been accessible.
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