ArticleBlood2013
Targeted nanoparticle delivery overcomes off-target immunostimulatory effects of oligonucleotides and improves therapeutic efficacy in chronic lymphocytic leukemia.
Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
29 citing papers in PubMed, 64 citations in OpenAlex.
- Potential New Therapies "ROS-Based" in CLL: An Innovative Paradigm in the Induction of Tumor Cell Apoptosis.Antioxidants (Basel, Switzerland) · 2024Review
- Targeting ferroptosis for leukemia therapy: exploring novel strategies from its mechanisms and role in leukemia based on nanotechnology.European journal of medical research · 2024Review
- Versatility of Liposomes for Antisense Oligonucleotide Delivery: A Special Focus on Various Therapeutic Areas.Pharmaceutics · 2023Review
- From Nanoparticles to Cancer Nanomedicine: Old Problems with New Solutions.Nanomaterials (Basel, Switzerland) · 2021Review
- Molecular Perspective of Nanoparticle Mediated Therapeutic Targeting in Breast Cancer: An Odyssey of Endoplasmic Reticulum Unfolded Protein Response (UPRBiomedicines · 2021Review
- Nanocarriers as Magic Bullets in the Treatment of Leukemia.Nanomaterials (Basel, Switzerland) · 2020Review
- Article
- Nanoparticles for hematologic diseases detection and treatment.Hematology & medical oncology · 2019Article
- Optimizing Advances in Nanoparticle Delivery for Cancer Immunotherapy.Advanced drug delivery reviews · 2019Review
- Vector-independent transmembrane transport of oligodeoxyribonucleotides involves p38 mitogen activated protein kinase phosphorylation.Scientific reports · 2017Article
- Comparative analysis of metallic nanoparticles as exogenous soft tissue contrast for live in vivo micro-computed tomography imaging of avian embryonic morphogenesis.Developmental dynamics : an official publication of the American Association of Anatomists · 2016Article
- Injection site reactions after subcutaneous oligonucleotide therapy.British journal of clinical pharmacology · 2016Review
- CD20-targeting in B-cell malignancies: novel prospects for antibodies and combination therapies.Investigational new drugs · 2016Review
- Epigenetic Control of B Cell Development and B-Cell-Related Immune Disorders.Clinical reviews in allergy & immunology · 2016Review
- Current understanding of interactions between nanoparticles and the immune system.Toxicology and applied pharmacology · 2016Review
- Pre-clinical immunotoxicity studies of nanotechnology-formulated drugs: Challenges, considerations and strategy.Journal of controlled release : official journal of the Controlled Release Society · 2015Review
- Nanomedicine and drug delivery strategies for treatment of inflammatory bowel disease.World journal of gastroenterology · 2015Review
- miR-181b as a therapeutic agent for chronic lymphocytic leukemia in the Eµ-TCL1 mouse model.Oncotarget · 2015Article
- Review
- Cell type-specific delivery of short interfering RNAs by dye-functionalised theranostic nanoparticles.Nature communications · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
Several RNA-targeted therapeutics, including antisense oligonucleotides (ONs), small interfering RNAs, and miRNAs, constitute immunostimulatory CpG motifs as an integral part of their design. The limited success with free antisense ONs in hematologic malignancies in recent clinical trials has been attributed to the CpG motif-mediated, TLR-induced prosurvival effects and inefficient target modulation in desired cells. In an attempt to diminish their off-target prosurvival and proinflammatory effects and specific delivery, as a proof of principle, in the present study, we developed an Ab-targeted liposomal delivery strategy using a clinically relevant CD20 Ab (rituximab)-conjugated lipopolyplex nanoparticle (RIT-INP)- and Bcl-2-targeted antisense G3139 as archetypical antisense therapeutics. The adverse immunostimulatory responses were abrogated by selective B cell-targeted delivery and early endosomal compartmentalization of G3139-encapsulated RIT-INPs, resulting in reduced NF-κB activation, robust Bcl-2 down-regulation, and enhanced sensitivity to fludarabine-induced cytotoxicity. Furthermore, significant in vivo therapeutic efficacy was noted after RIT-INP-G3139 administration in a disseminated xenograft leukemia model. The results of the present study demonstrate that CD20-targeted delivery overcomes the immunostimulatory properties of CpG-containing ON therapeutics and improves efficient gene silencing and in vivo therapeutic efficacy for B-cell malignancies. The broader implications of similar approaches in overcoming immunostimulatory properties of RNA-directed therapeutics in hematologic malignancies are also discussed.
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What OpenQuestion 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 OpenQuestion graph.