ArticleRNA nanomed2024
pH-responsive bond as a linker for the release of chemical drugs from RNA-drug complexes in endosome or lysosome.
Article in RNA nanomed, 2024. 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.
- Conjugation of hydrophobic drugs to motile pRNA 4WJ nanoparticles for spontaneous tumor targeting and undetectable toxicity.Nature protocols · 2026Review
- Developing Potent Therapeutics for Liver Cancer Chemoresistance via an RNA Nanotech and Series-Circuit-Christmas-Bulb Mechanism Targeting ABC Transporters.Molecular pharmaceutics · 2026Review
- Nanomedicine delivery systems remodel the immunosuppressive microenvironment of colorectal cancer: synergistic strategies and mechanisms of targeted immune checkpoint inhibitors.Frontiers in immunology · 2026Review
- Lysosome as a Chemical Reactor.International journal of molecular sciences · 2025Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Emerging phenomena have signaled that RNA therapeutics will be the third milestone in pharmaceutical drug development. RNA nanoparticles display motile and deformable properties that lead to (1) fast and efficient tumor accumulation via both spontaneous and active targeting, and (2) fast renal excretion of non-tumor-accumulated nanoparticles due to RNA's negative charge and dynamic property; thus, undetectable toxicity. Here, we report the use of RNA nanoparticles to harbor the cancer-targeting ligand and chemical drugs and the design of the pH-responsive bond as a linker for the release of chemical drugs from RNA-drug complexes in endosomes or lysosomes. RNA nanoparticles constructed from a three-way junction (3WJ) core of bacteriophage phi29 packaging RNA (pRNA) offer an advanced strategy for receptor-selective drug delivery into cancer cells and has the potential to enhance the efficacy of anti-cancer therapies while mitigating dose-limiting toxicity in patients with colorectal cancer (CRC). We investigated conjugation of small-molecule drugs targeting the PI3K/mTOR pathway to 3WJ RNA nanoparticles and confirmed intracellular drug delivery by 3WJ RNA nanoparticles into CRC cells. 3WJ a, a single strand of 3WJ nanoparticle, was constructed with a pH-sensitive linkage conjugated to a dual PI3K/mTOR inhibitor, PI-103-azide. We demonstrated PI-103 conjugation to RNA under normal physiologic pH conditions and rapid pH-dependent drug release in an acidic environment. Next, we assembled FA-3WJ-PI103 nanoparticles from three single-stranded RNA, 3WJ a-PI-103, 3WJ b and 3WJ c-folate, to specifically target folate receptor alpha (FRα). Our tests demonstrated receptor-mediated uptake of FA-pRNA-PI-103 nanoparticles, pH-responsive PI-103 drug release from lysosomes and inhibition of the PI3K/mTOR pathway in CRC cells and tumor spheroids. These results confirm receptor-mediated cytosolic drug delivery by pH-responsive RNA nanoparticles and demonstrate potential of the 3WJ-drug complex as a novel strategy for receptor-selective drug delivery to cancer cells with high FRα expression.
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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.