ArticleACS nano2013
Two-wave nanotherapy to target the stroma and optimize gemcitabine delivery to a human pancreatic cancer model in mice.
Article in ACS nano, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.
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
75 citing papers in PubMed, 1 synthesis or guideline pooled it, 186 citations in OpenAlex.
- Signaling pathway mechanisms in pancreatic ductal adenocarcinoma tumor microenvironment and emerging targeting strategies for improved prognosis.Oncology reviews · 2026Pooled it
- Clinical validation of a nanodiamond-embedded thermoplastic biomaterial.Proceedings of the National Academy of Sciences of the United States of America · 2017Trial
- Breaking barriers: nano-boosted drug delivery systems in overcoming the defenses of pancreatic cancer.Molecular cancer · 2026Review
- Stromal homeostasis-restoring "rocket-like" nanomedicine inhibited pancreatic tumor growth in vivo.Materials today. Bio · 2026Article
- Targeted drug delivery systems for pancreatic cancer therapy: advances, challenges, and future perspectives.Frontiers in immunology · 2026Review
- Review
- Nanocarriers for Combination Therapy in Pancreatic Ductal Adenocarcinoma: A Comprehensive Review.Nanomaterials (Basel, Switzerland) · 2025Review
- Feasibility analysis and development trend of nanomaterials for the treatment of pancreatic cancer.Discover nano · 2025Review
- Extensive Review of Nanomedicine Strategies Targeting the Tumor Microenvironment in PDAC.International journal of nanomedicine · 2025Review
- Exploring and Analyzing the Systemic Delivery Barriers for Nanoparticles.Advanced functional materials · 2024Article
- Bioactive Glasses as Carriers of Cancer-Targeted Drugs: Challenges and Opportunities in Bone Cancer Treatment.Materials (Basel, Switzerland) · 2022Review
- Review
- A Space-Time Conversion Vehicle for Programmed Multi-Drugs Delivery into Pancreatic Tumor to Overcome Matrix and Reflux Barriers.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Nanomedicine Penetration to Tumor: Challenges, and Advanced Strategies to Tackle This Issue.Cancers · 2022Review
- Review
- Stromal disruption facilitating invasion of a 'nano-arsenal' into the solid tumor.Drug discovery today · 2022Review
- Local Release of TGF-β Inhibitor Modulates Tumor-Associated Neutrophils and Enhances Pancreatic Cancer Response to Combined Irreversible Electroporation and Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Mesoporous Silica Nanoparticle-Based Drug Delivery Systems for the Treatment of Pancreatic Cancer: A Systematic Literature Overview.Pharmaceutics · 2022Review
- Emerging pro-drug and nano-drug strategies for gemcitabine-based cancer therapy.Asian journal of pharmaceutical sciences · 2022Review
- Nanomaterial-Based Drug Delivery Systems: A New Weapon for Cancer Immunotherapy.International journal of nanomedicine · 2022Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) elicits a dense stromal response that blocks vascular access because of pericyte coverage of vascular fenestrations. In this way, the PDAC stroma contributes to chemotherapy resistance in addition to causing other problems. In order to improve the delivery of gemcitabine, a first-line chemotherapeutic agent, a PEGylated drug-carrying liposome was developed, using a transmembrane ammonium sulfate gradient to encapsulate the protonated drug up to 20% w/w. However, because the liposome was precluded from entering the xenograft site due to the stromal interference, we developed a first-wave nanocarrier that decreases pericyte coverage of the vasculature through interference in the pericyte recruiting TGF-β signaling pathway. This was accomplished using a polyethyleneimine (PEI)/polyethylene glycol (PEG)-coated mesoporous silica nanoparticle (MSNP) for molecular complexation to a small molecule TGF-β inhibitor, LY364947. LY364947 contains a nitrogen atom that attaches, through H-bonding, to PEI amines with a high rate of efficiency. The copolymer coating also facilitates systemic biodistribution and retention at the tumor site. Because of the high loading capacity and pH-dependent LY364947 release from the MSNPs, we achieved rapid entry of IV-injected liposomes and MSNPs at the PDAC tumor site. This two-wave approach provided effective shrinkage of the tumor xenografts beyond 25 days, compared to the treatment with free drug or gemcitabine-loaded liposomes only. Not only does this approach overcome stromal resistance to drug delivery in PDAC, but it also introduces the concept of using a stepwise engineered approach to address a range of biological impediments that interfere in nanocancer therapy in a spectrum of cancers.
Indexed as
Identifiers
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.