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Updated: May 5, 2026
Manufacture and Drug Delivery Applications of Silk Nanoparticles
Published on: October 8, 2016
Tumour-derived small extracellular vesicles act as a barrier to therapeutic nanoparticle delivery
Ningqiang Gong1,2, Wenqun Zhong3, Mohamad-Gabriel Alameh4
1Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
Abstract:
Nanoparticles are promising for drug delivery applications, with several clinically approved products. However, attaining high nanoparticle accumulation in solid tumours remains challenging. Here we show that tumour cell-derived small extracellular vesicles (sEVs) block nanoparticle delivery to tumours, unveiling another barrier to nanoparticle-based tumour therapy. Tumour cells secrete large amounts of sEVs in the tumour microenvironment, which then bind to nanoparticles entering tumour tissue and traffic them to liver Kupffer cells for degradation. Knockdown of Rab27a, a gene that controls sEV secretion, decreases sEV levels and improves nanoparticle accumulation in tumour tissue. The therapeutic efficacy of messenger RNAs encoding tumour suppressing and proinflammatory proteins is greatly improved when co-encapsulated with Rab27a small interfering RNA in lipid nanoparticles. Together, our results demonstrate that tumour cell-derived sEVs act as a defence system against nanoparticle tumour delivery and that this system may be a potential target for improving nanoparticle-based tumour therapies.
Insights
Tumor cells release small extracellular vesicles (sEVs) that hinder nanoparticle drug delivery. Inhibiting sEVs with Rab27a knockdown enhances nanoparticle accumulation and therapeutic efficacy in tumors.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Biology
Background:
- Nanoparticles show promise for drug delivery, with clinical applications existing.
- Achieving high nanoparticle accumulation in solid tumors is a significant challenge in cancer therapy.
Purpose of the Study:
- To investigate the role of tumor cell-derived small extracellular vesicles (sEVs) in nanoparticle delivery to tumors.
- To identify sEVs as a barrier to nanoparticle-based tumor therapy and explore strategies to overcome it.
Main Methods:
- Investigated the interaction between nanoparticles and tumor cell-derived sEVs in the tumor microenvironment.
- Utilized gene knockdown of Rab27a to reduce sEV secretion.
- Assessed nanoparticle accumulation in tumors and therapeutic efficacy of co-delivered mRNA and siRNA in lipid nanoparticles.
Main Results:
- Tumor cell-derived sEVs bind to nanoparticles and traffic them to liver Kupffer cells for degradation, blocking tumor delivery.
- Knockdown of Rab27a significantly reduced sEV levels, leading to improved nanoparticle accumulation in tumors.
- Co-encapsulation of therapeutic mRNAs with Rab27a small interfering RNA in lipid nanoparticles enhanced therapeutic efficacy.
Conclusions:
- Tumor cell-derived sEVs function as a defense mechanism impeding nanoparticle delivery to tumors.
- Targeting sEV secretion presents a potential strategy to enhance nanoparticle-based tumor therapies.
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