ArticleChemistry of materials : a publication of the American Chemical Society2025
Multifunctional Polypeptide-Based Nanoconjugates for Targeted Mitochondrial Delivery and Nonviral Gene Therapy.
Article in Chemistry of materials : a publication of the American Chemical Society, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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Who cites it
4 citing papers in PubMed.
- Synthesis and biological study of thiopheneyl/piperazinl-α-aminophosphonate-chitosan conjugates as biologically active carriers for controlled delivery of curcumin.Scientific reports · 2026Article
- Self-Assembling Short Peptide Carriers for Gene Delivery.International journal of molecular sciences · 2026Review
- A worm-like nucleic acid nanostructure for gene delivery and endosomal escape via ClC3 ion exchanger.Science advances · 2026Article
- In vitro Evaluation of Mitochondrial-Targeted Andrographolide Nanoparticles Against 4T1 Breast Cancer Cells.International journal of nanomedicine · 2025Article
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite recent advances in nanomedicine, developing multifunctional nanocarriers capable of targeted subcellular delivery and efficient gene therapy remains a significant challenge. This study reports the design, synthesis, and evaluation of a novel multifunctional polypeptide-based nanoconjugate that addresses this gap using sequential delivery, combining mitochondrial targeting and nonviral gene therapy. We engineered a poly-l-ornithine-based, polyethylene glycol-modified carrier and introduced a novel custom-designed trivalent compound (TRV3) into the structure. TRV3, conjugated to the polypeptide carrier via a redox-sensitive disulfide linker, incorporates the well-described triphenylphosphonium moiety (TPP) for mitochondrial targeting and a Cy5 fluorophore as a model drug. The resulting nanoconjugate (C-TRV3-A) demonstrated efficient endosomal escape and mitochondrial localization. Leveraging the endosomolytic properties of C-TRV3-A, we explored its potential as a nonviral vector for gene therapy. After optimizing formulation stability using a VLC-3 anionic polypeptide coating, we developed plasmid DNA polyplexes that exhibited enhanced stability and transfection efficiency in basic and advanced triple-negative breast cancer cell culture models. This multifunctional polypeptide-based nanoconjugate represents a significant advance in the field, offering a chemically versatile platform for simultaneous subcellular targeting and gene delivery that may be used in targeted cancer treatments, among other pathologies.
Identifiers
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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 Socratic graph.