ArticleProceedings of the National Academy of Sciences of the United States of America2023
In vivo bone marrow microenvironment siRNA delivery using lipid-polymer nanoparticles for multiple myeloma therapy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
30 citing papers in PubMed, 48 citations in OpenAlex.
- 25+ Years of TRPV4: From Discovery to Translational Horizons.Research square · 2026Article
- The RNA delivery dilemma-lipid versus polymer nanoparticle platforms.Drug delivery and translational research · 2026Article
- Nanoparticle Strategies for Bone Metastasis Immunotherapy: Targeting, Immune Reprogramming and Combination Therapy.Pharmaceutics · 2026Review
- In vivo genome editing of human haematopoietic stem cells for treatment of blood disorders using mRNA delivery.Nature biomedical engineering · 2026Article
- Dysregulated Bone Marrow Contributes to Glomerular Injury through Soluble Factors.Journal of the American Society of Nephrology : JASN · 2026Article
- RNA-Based Therapeutic Strategies in Multiple Myeloma: From Molecular Targets to Delivery and Clinical Translation.International journal of molecular sciences · 2026Review
- Nanomedicine-Empowered CAR-T Therapy for Multiple Myeloma: Toward Programmable, Durable, and Precision Immunotherapy.International journal of nanomedicine · 2026Review
- Nanogel-Based Precision Bone Regeneration: Rational Design, Biological Barrier Penetration, and Osteoporotic Microenvironment Remodeling.International journal of nanomedicine · 2026Review
- Plasma Cell Myeloma: Biochemical Insights into Diagnosis, Treatment, and Smart Nanocarrier-Based Therapeutic Development.Pharmaceutics · 2025Review
- Lipid nanoparticles: a promising tool for nucleic acid delivery in cancer immunotherapy.Medical oncology (Northwood, London, England) · 2025Review
- Breaking Barriers: The Role of the Bone Marrow Microenvironment in Multiple Myeloma Progression.International journal of molecular sciences · 2025Review
- CD47 peptide-cloaked lipid nanoparticles promote cell-specific mRNA delivery.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Nature-inspired platform nanotechnology for RNA delivery to myeloid cells and their bone marrow progenitors.Nature nanotechnology · 2025Article
- Sequential dual-targeting biomimetic nanovesicles for bone marrow-specific delivery of bortezomib in multiple myeloma.Frontiers in bioengineering and biotechnology · 2025Article
- A QUARTER CENTURY OF CALCIUM-PERMEABLE ION CHANNEL, TRPV4: PERSPECTIVES ON EXPRESSION AND FUNCTION IN ENDOTHELIAL CELLS-TIME TO TRANSLATE.Transactions of the American Clinical and Climatological Association · 2025Review
- Advancing Cancer Immunotherapy Using Lipid Nanoparticle-Based Approaches.International journal of nanomedicine · 2025Review
- Recent advances in targeted drug delivery systems for multiple myeloma.Journal of controlled release : official journal of the Controlled Release Society · 2024Review
- Enhancing RNA-lipid nanoparticle delivery: Organ- and cell-specificity and barcoding strategies.Journal of controlled release : official journal of the Controlled Release Society · 2024Review
- Optimized microfluidic formulation and organic excipients for improved lipid nanoparticle mediated genome editing.Lab on a chip · 2024Article
- Lymphoid organ-targeted nanomaterials for immunomodulation of cancer, inflammation, and beyond.Chemical Society reviews · 2024Review
Corrections and comments
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Authors and funding
18 authors at 10 institutions in 3 countries.
Funding
Abstract
Multiple myeloma (MM), a hematologic malignancy that preferentially colonizes the bone marrow, remains incurable with a survival rate of 3 to 6 mo for those with advanced disease despite great efforts to develop effective therapies. Thus, there is an urgent clinical need for innovative and more effective MM therapeutics. Insights suggest that endothelial cells within the bone marrow microenvironment play a critical role. Specifically, cyclophilin A (CyPA), a homing factor secreted by bone marrow endothelial cells (BMECs), is critical to MM homing, progression, survival, and chemotherapeutic resistance. Thus, inhibition of CyPA provides a potential strategy to simultaneously inhibit MM progression and sensitize MM to chemotherapeutics, improving therapeutic response. However, inhibiting factors from the bone marrow endothelium remains challenging due to delivery barriers. Here, we utilize both RNA interference (RNAi) and lipid-polymer nanoparticles to engineer a potential MM therapy, which targets CyPA within blood vessels of the bone marrow. We used combinatorial chemistry and high-throughput in vivo screening methods to engineer a nanoparticle platform for small interfering RNA (siRNA) delivery to bone marrow endothelium. We demonstrate that our strategy inhibits CyPA in BMECs, preventing MM cell extravasation in vitro. Finally, we show that siRNA-based silencing of CyPA in a murine xenograft model of MM, either alone or in combination with the Food and Drug Administration (FDA)-approved MM therapeutic bortezomib, reduces tumor burden and extends survival. This nanoparticle platform may provide a broadly enabling technology to deliver nucleic acid therapeutics to other malignancies that home to bone marrow.
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What Socratic holds
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.