ArticleFrontiers in oncology2020
PD-L1 siRNA Theranostics With a Dextran Nanoparticle Highlights the Importance of Nanoparticle Delivery for Effective Tumor PD-L1 Downregulation.
Article in Frontiers in oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Molecular signatures of breast cancer in the Iranian population: a review of cell growth and cell cycle regulators.Journal of cancer research and clinical oncology · 2025Pooled it
- Engineered exosomes for breast cancer immunotherapy: Emerging strategies and translational potential.Biochemistry and biophysics reports · 2026Review
- Glucan-Based Nanoparticles Empower Precision Cancer Immunotherapy: Design Strategies, Immune Reprogramming Mechanisms, and Clinical Translation Prospects.International journal of nanomedicine · 2026Review
- Targeting tumor immune evasion: the role of PD-L1 siRNA in advancing cancer immunotherapy.Medical oncology (Northwood, London, England) · 2025Review
- Targeting breast tumor extracellular matrix and stroma utilizing nanoparticles.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Nanotechnology Applications in Breast Cancer Immunotherapy.Small (Weinheim an der Bergstrasse, Germany) · 2024Review
- Nanoparticle-Mediated Immunotherapy in Triple-Negative Breast Cancer.ACS biomaterials science & engineering · 2024Review
- Nano-immunotherapy: overcoming delivery challenge of immune checkpoint therapy.Journal of nanobiotechnology · 2023Review
- The use of RNA-based treatments in the field of cancer immunotherapy.Molecular cancer · 2023Review
- PSMA-specific degradable dextran for multiplexed immunotargeted siRNA therapeutics against prostate cancer.Nanoscale · 2022Article
- Neuroimmune crosstalk and its impact on cancer therapy and research.Discover oncology · 2022Review
- VEGF Overexpression Significantly Increases Nanoparticle-Mediated siRNA Delivery and Target-Gene Downregulation.Pharmaceutics · 2022Article
- Targeting the PD-1/PD-L1 axis for cancer treatment: a review on nanotechnology.Royal Society open science · 2022Review
- Critical review of nucleic acid nanotechnology to identify gaps and inform a strategy for accelerated clinical translation.Advanced drug delivery reviews · 2022Review
- Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
purposeThe inhibition of immune checkpoints such as programmed cell death ligand-1 (PD-L1/CD274) with antibodies is providing novel opportunities to expose cancer cells to the immune system. Antibody based checkpoint blockade can, however, result in serious autoimmune complications because normal tissues also express immune checkpoints. As sequence-specific gene-silencing agents, the availability of siRNA has significantly expanded the specificity and range of "druggable" targets making them promising agents for precision medicine in cancer. Here, we have demonstrated the ability of a novel biodegradable dextran based theranostic nanoparticle (NP) to deliver siRNA downregulating PD-L1 in tumors. Optical imaging highlighted the importance of NP delivery and accumulation in tumors to achieve effective downregulation with siRNA NPs, and demonstrated low delivery and accumulation in several PD-L1 expressing normal tissues.
methodsThe dextran scaffold was functionalized with small molecules containing amine groups through acetal bonds. The NP was decorated with a Cy5.5 NIR probe allowing visualization of NP delivery, accumulation, and biodistribution. MDA-MB-231 triple negative human breast cancer cells were inoculated orthotopically or subcutaneously to achieve differences in vascular delivery in the tumors. Molecular characterization of PD-L1 mRNA and protein expression in cancer cells and tumors was performed with qRT-PCR and immunoblot analysis.
resultsThe PD-L1 siRNA dextran NPs effectively downregulated PD-L1 in MDA-MB-231 cells. We identified a significant correlation between NP delivery and accumulation, and the extent of PD-L1 downregulation, with
conclusionsHere we have demonstrated, for the first time, the feasibility of downregulating PD-L1 in tumors using siRNA delivered with a biodegradable dextran polymer that was decorated with an imaging reporter. Our data demonstrate the importance of tumor NP delivery and accumulation in achieving effective downregulation, highlighting the importance of imaging in siRNA NP delivery. Effective delivery of these siRNA carrying NPs in the tumor but not in normal tissues may mitigate some of the side-effects of immune checkpoint inhibitors by sparing PD-L1 inhibition in these tissues.
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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 OpenQuestion graph.