ArticleMolecular therapy. Nucleic acids2017
Cholesterol-Containing Nuclease-Resistant siRNA Accumulates in Tumors in a Carrier-free Mode and Silences MDR1 Gene.
Article in Molecular therapy. Nucleic acids, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 82 citations in OpenAlex.
- 1'-Sugar-Tethered Cholesterol-Modified siRNAs with Variable Linker Lengths for Carrier-Free Delivery and Enhanced RNAi Efficiency.ACS omega · 2026Article
- Sequence-Defined Digital Bottlebrush Polymers for Programmable Oligonucleotide Delivery.bioRxiv : the preprint server for biology · 2026Article
- Review
- Lung-targeted RNA delivery systems: strategies and therapeutic applications.Journal of nanobiotechnology · 2026Review
- Knocking on Cells' Door: Strategic Approaches for miRNA and siRNA in Anticancer Therapy.International journal of molecular sciences · 2025Review
- Redesigning miR-34a: structural and chemical advances in the therapeutic development of an miRNA anti-cancer agent.Biochemical Society transactions · 2025Article
- piRNA28846 has the potential to be a novel RNA nucleic acid drug for ovarian cancer.NPJ precision oncology · 2025Article
- Lipid-siRNA Conjugates Targeting High PD-L1 Expression as Potential Novel Immune Checkpoint Inhibitors.Biomolecules · 2025Article
- Advancing cancer treatments: The role of oligonucleotide-based therapies in driving progress.Molecular therapy. Nucleic acids · 2024Review
- Article
- Structural optimization of siRNA conjugates for albumin binding achieves effective MCL1-directed cancer therapy.Nature communications · 2024Article
- Cholesterol Conjugates of Small Interfering RNA: Linkers and Patterns of Modification.Molecules (Basel, Switzerland) · 2024Article
- Influence of Combinations of Lipophilic and Phosphate Backbone Modifications on Cellular Uptake of Modified Oligonucleotides.Molecules (Basel, Switzerland) · 2024Article
- Self-Penetrating Oligonucleotide Derivatives: Features of Self-Assembly and Interactions with Serum and Intracellular Proteins.Pharmaceutics · 2023Article
- Fork- and Comb-like Lipophilic Structures: Different Chemical Approaches to the Synthesis of Oligonucleotides with Multiple Dodecyl Residues.International journal of molecular sciences · 2023Article
- Nucleic acid amphiphiles: Synthesis, properties, and applications.Molecular therapy. Nucleic acids · 2023Review
- The emerging potential of siRNA nanotherapeutics in treatment of arthritis.Asian journal of pharmaceutical sciences · 2023Review
- Extracellular Vesicles for Therapeutic Nucleic Acid Delivery: Loading Strategies and Challenges.International journal of molecular sciences · 2023Review
- Enhancing the Effectiveness of Oligonucleotide Therapeutics Using Cell-Penetrating Peptide Conjugation, Chemical Modification, and Carrier-Based Delivery Strategies.Pharmaceutics · 2023Review
- MicroRNAs of Milk in Cells, Plasma, and Lipid Fractions of Human Milk, and Abzymes Catalyzing Their Hydrolysis.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemical modifications are an effective way to improve the therapeutic properties of small interfering RNAs (siRNAs), making them more resistant to degradation in serum and ensuring their delivery to target cells and tissues. Here, we studied the carrier-free biodistribution and biological activity of a nuclease-resistant anti-MDR1 cholesterol-siRNA conjugate in healthy and tumor-bearing severe combined immune deficiency (SCID) mice. The attachment of cholesterol to siRNA provided its efficient accumulation in the liver and in tumors, and reduced its retention in the kidneys after intravenous and intraperitoneal injection. The major part of cholesterol-siRNA after intramuscular and subcutaneous injections remained in the injection place. Confocal microscopy data demonstrated that cholesterol-siRNA spread deep in the tissue and was present in the cytoplasm of almost all the liver and tumor cells. The reduction of P-glycoprotein level in human KB-8-5 xenograft overexpressing the MDR1 gene by 60% was observed at days 5-6 after injection. Then, its initial level recovered by the eighth day. The data showed that, regardless of the mode of administration (intravenous, intraperitoneal, or peritumoral), cholesterol-siMDR efficiently reduced the P-glycoprotein level in tumors. The designed anti-MDR1 conjugate has potential as an adjuvant therapeutic for the reversal of multiple drug resistance of cancer cells.
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