Reversal of pancreatic desmoplasia by re-educating stellate cells with a tumour microenvironment-activated nanosystem
Open accessAbstract
Pancreatic ductal adenocarcinoma is characterised by a dense desmoplastic stroma composed of stromal cells and extracellular matrix (ECM). This barrier severely impairs drug delivery and penetration. Activated pancreatic stellate cells (PSCs) play a key role in establishing this unique pathological obstacle, but also offer a potential target for anti-tumour therapy. Here, we construct a tumour microenvironment-responsive nanosystem, based on PEGylated polyethylenimine-coated gold nanoparticles, and utilise it to co-deliver all- trans retinoic acid (ATRA, an inducer of PSC quiescence) and siRNA targeting heat shock protein 47 (HSP47, a collagen-specific molecular chaperone) to re-educate PSCs. The nanosystem simultaneously induces PSC quiescence and inhibits ECM hyperplasia, thereby promoting drug delivery to pancreatic tumours and significantly enhancing the anti-tumour efficacy of chemotherapeutics. Our combination strategy to restore homoeostatic stromal function by targeting activated PSCs represents a promising approach to improving the efficacy of chemotherapy and other therapeutic modalities in a wide range of stroma-rich tumours.
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In a relatively low number of formulations, RA was immobilized on the surface of the nanoparticle; the concentration of RA immobilized on the surface is lower than in the core.
“In a relatively low number of formulations, RA was immobilized not in the core but on the surface of the nanoparticle22; however, the concentration of RA immobilized on the surface is lower than in the core.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [22]
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References 68 · Cited by 339
- Authors
- Han, X., Li, Y., Xu, Y., Zhao, X., Zhang, Y., Yang, X., Wang, Y., Zhao, R., Anderson, G. J., Zhao, Y., & Nie, G.
- Affiliations
- Chinese Academy of Sciences (CN)
- National Center for Nanoscience and Technology (CN)
- QIMR Berghofer Medical Research Institute (AU)
- Corresponding author
- Li, Yiye
- Zhao, Yuliang
- Nie, Guangjun
- ORCID
- Venue
- Nature Communications
- Published
- 2018-08-23
- Volume
- 9
- Issue
- 1
- Pages
- 3390-3390
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6107580
- OpenAlex
- W2885761217
- Cited by
- 339
- References
- 68
- Citations by year
- 2026: 22 · 2025: 34 · 2024: 39 · 2023: 43 · 2022: 52 · 2021: 57 · 2020: 61 · 2019: 30 · 2018: 1
- FWCI
- 14.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Academy of Medical Sciences (NAF003\1002)
- National Natural Science Foundation of China (31571021, 11621505, 91543127, QYZDJ‐SSW‐SLH022, 31661130152, 31325010, 31730032, 2018YFA0208900)
- Chinese Academy of Sciences (31730032, 2018YFA0208900, 11621505, QYZDJ-SSW-SLH022)
- Beijing Municipal Science and Technology Commission (Z161100000116035)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- pancreatic ductal adenocarcinoma, pancreatic stellate cells, tumor microenvironment, gold nanoparticles, all-trans retinoic acid, siRNA delivery, HSP47, extracellular matrix, drug delivery, chemotherapy efficacy
- MeSH terms
- Animals, Cell Cycle, Endocytosis, Extracellular Matrix, Female, Gold, Homeostasis, Humans, Hydrogen-Ion Concentration, Mice, Inbred BALB C, Mice, Nude, Pancreatic Neoplasms, Polyethylene Glycols, Polyethyleneimine, Tissue Distribution, Tretinoin, Stromal Cells, Spheroids, Cellular, Gene Silencing, Xenograft Model Antitumor Assays, RNA, Small Interfering, Metal Nanoparticles, Pancreatic Stellate Cells, Tumor Microenvironment
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