ArticleIntegrative biology : quantitative biosciences from nano to macro2009
Systemic in vivo distribution of activatable cell penetrating peptides is superior to that of cell penetrating peptides.
Article in Integrative biology : quantitative biosciences from nano to macro, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
85 citing papers in PubMed, 194 citations in OpenAlex.
- Interactions of Antibody Drug Conjugate Anti-Tubulin and Topoisomerase I Inhibitor Payloads with Radiotherapy to Potentiate Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Development of Cathepsin B‑Activatable Cell-Penetrating Peptides for Tumor Targeting.ACS pharmacology & translational science · 2026Article
- Orthogonally targeted tumor radiosensitization using cell penetrating peptide-ATM inhibitor conjugates to stimulate anti-tumor immune responses.bioRxiv : the preprint server for biology · 2026Article
- Analytical Insights and Biomedical Applications of Homing Penetrating Peptides in Cancer.Advances in experimental medicine and biology · 2026Article
- Peptide hydrogel-drug conjugates for tailored disease treatment.Materials today. Bio · 2025Review
- Biological Properties of Arginine-rich Peptides and their Application in Cargo Delivery to Cancer.Current drug delivery · 2025Review
- Bismuth-Cyclized Cell-Penetrating Peptides.Molecular pharmaceutics · 2024Article
- Cell-Penetrating and Enzyme-Responsive Peptides for Targeted Cancer Therapy: Role of Arginine Residue Length on Cell Penetration and In Vivo Systemic Toxicity.ACS applied materials & interfaces · 2024Article
- Brain-targeted intranasal delivery of protein-based gene therapy for treatment of ischemic stroke.Theranostics · 2024Article
- Peptide-Based siRNA Nanocomplexes Targeting Hepatic Stellate Cells.Biomolecules · 2023Article
- Mitochondrial adaptation in cancer drug resistance: prevalence, mechanisms, and management.Journal of hematology & oncology · 2022Review
- Accum™ Technology: A Novel Conjugable Primer for Onco-Immunotherapy.Molecules (Basel, Switzerland) · 2022Review
- The role of cell-penetrating peptides in potential anti-cancer therapy.Clinical and translational medicine · 2022Review
- Deep Learning Enables Discovery of a Short Nuclear Targeting Peptide for Efficient Delivery of Antisense Oligomers.JACS Au · 2021Article
- Efficient intracellular delivery of proteins by a multifunctional chimaeric peptide in vitro and in vivo.Nature communications · 2021Article
- CPPs to the Test: Effects on Binding, Uptake and Biodistribution of a Tumor Targeting Nanobody.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Hybrid Cyclobutane/Proline-Containing Peptidomimetics: The Conformational Constraint Influences Their Cell-Penetration Ability.International journal of molecular sciences · 2021Article
- Hexokinase 2 in Cancer: A Prima Donna Playing Multiple Characters.International journal of molecular sciences · 2021Review
- Article
- Chiral Cyclobutane-Containing Cell-Penetrating Peptides as Selective Vectors for Anti-International journal of molecular sciences · 2020Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Cell penetrating peptides (CPPs) have been developed as vehicles for payload delivery into cells in culture and in animals. However several biologic features limit their usefulness in living animals. Activatable cell penetrating peptides (ACPPs) are polycationic CPPs whose adsorption and cellular uptake are minimized by a covalently attached polyanionic inhibitory domain. Cleavage of the linker connecting the polyanionic and polycationic domains by specific proteases (tumor associated matrix metalloproteases discussed herein) dissociates the polyanion and enables the cleaved ACPP to enter cells. In contrast to their CPP counterpart, ACPPs are relatively nonadherent and distributed uniformly to normal tissues. While nonaarginine (r(9)) CPP administered intravenously into mice initially bind to the local vasculature and redistribute to the liver, where >90% of the injected dose accumulates 30 min after injection. Regardless of the presence of the polyanionic inhibitory domain, confocal imaging of live tissues reveals that the majority of the ACPP and CPP remain in punctate organelles, presumably endosomes. Therefore further improvements in the efficiency of delivery to the cytosol and nucleus are necessary. In addition to improved target specificity, a major advantage of ACPPs over CPPs for potential clinical applications is reduced toxicity. Systemically administered r(9) CPP causes acute toxicity in mice at a dose 4-fold lower than the MMP cleavable ACPP, a complication not observed with an uncleavable ACPP presumably because the polycationic charge remains masked systemically. These data suggest that ACPPs have greater potential than CPPs for systemic delivery of imaging and therapeutic agents.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.