ArticleBioconjugate chemistry2015
Dual peptide conjugation strategy for improved cellular uptake and mitochondria targeting.
Article in Bioconjugate chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Combining Leu-enkephalin nanomedicines with enkephalinase inhibitors: a promising painkiller strategy?Drug delivery and translational research · 2026Article
- Recent Advances in the Application of Mitochondria-targeted Fluorescent Probes.Current medicinal chemistry · 2025Review
- The Role and Applied Value of Mitochondria in Glioma-Related Research.CNS neuroscience & therapeutics · 2024Review
- Recent advances in mitochondria-targeting theranostic agents.Exploration (Beijing, China) · 2024Review
- A Potential Effect of Circadian Rhythm in the Delivery/Therapeutic Performance of Paclitaxel-Dendrimer Nanosystems.Journal of functional biomaterials · 2023Article
- Unraveling mitochondria-targeting reactive oxygen species modulation and their implementations in cancer therapy by nanomaterials.Exploration (Beijing, China) · 2023Review
- Non-transgenic Gene ModulationACS nano · 2022Article
- Synthetic Molecular Evolution of Cell Penetrating Peptides.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Gallic acid-mitochondria targeting sequence-HThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2022Article
- Cell-Penetrating Peptides.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Peptide-Assisted Nucleic Acid Delivery Systems on the Rise.International journal of molecular sciences · 2021Review
- Development of Antimicrobial Stapled Peptides Based on Magainin 2 Sequence.Molecules (Basel, Switzerland) · 2021Article
- Dual-Functional Peptide Driven Liposome Codelivery System for Efficient Treatment of Doxorubicin-Resistant Breast Cancer.Drug design, development and therapy · 2021Article
- Polymeric Nanoparticles for Mitochondria Targeting Mediated Robust Cancer Therapy.Frontiers in bioengineering and biotechnology · 2021Review
- Mitochondria-Targeted Nanocarriers Promote Highly Efficient Cancer Therapy: A Review.Frontiers in bioengineering and biotechnology · 2021Review
- A peptide for transcellular cargo delivery: Structure-function relationship and mechanism of action.Journal of controlled release : official journal of the Controlled Release Society · 2020Article
- Direct Drug Targeting into Intracellular Compartments: Issues, Limitations, and Future Outlook.The Journal of membrane biology · 2019Review
- Cationic Surfactants: Self-Assembly, Structure-Activity Correlation and Their Biological Applications.International journal of molecular sciences · 2019Review
- Mitochondrial-Targeting Anticancer Agent Conjugates and Nanocarrier Systems for Cancer Treatment.Frontiers in pharmacology · 2018Review
- Self-assembling prodrugs.Chemical Society reviews · 2017Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Mitochondria are critical regulators of cellular function and survival. Delivery of therapeutic and diagnostic agents into mitochondria is a challenging task in modern pharmacology because the molecule to be delivered needs to first overcome the cell membrane barrier and then be able to actively target the intracellular organelle. Current strategy of conjugating either a cell penetrating peptide (CPP) or a subcellular targeting sequence to the molecule of interest only has limited success. We report here a dual peptide conjugation strategy to achieve effective delivery of a non-membrane-penetrating dye 5-carboxyfluorescein (5-FAM) into mitochondria through the incorporation of both a mitochondrial targeting sequence (MTS) and a CPP into one conjugated molecule. Notably, circular dichroism studies reveal that the combined use of α-helix and PPII-like secondary structures has an unexpected, synergistic contribution to the internalization of the conjugate. Our results suggest that although the use of positively charged MTS peptide allows for improved targeting of mitochondria, with MTS alone it showed poor cellular uptake. With further covalent linkage of the MTS-5-FAM conjugate to a CPP sequence (R8), the dually conjugated molecule was found to show both improved cellular uptake and effective mitochondria targeting. We believe these results offer important insight into the rational design of peptide conjugates for intracellular delivery.
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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.