Related Experiment Video
Updated: Jan 19, 2026
Micropatterned Surfaces to Study Hyaluronic Acid Interactions with Cancer Cells
Published on: December 22, 2010
Functional extracellular vesicles engineered with lipid-grafted hyaluronic acid effectively reverse cancer drug
Jia Liu1, Zhilan Ye1, Mengxi Xiang1
1Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Abstract:
Multidrug resistance (MDR) is a key issue accounting for ineffectiveness of cancer chemotherapy. Numerous multifunctional nanocarriers have been developed to increase drug delivery efficacy and inhibit drug efflux for overcoming cancer drug resistance. However, limited success has been achieved in clinic because of nanocarriers' complicated multi-step fabrication procedures and their undesired side toxicity as well as potential immunogenicity. Here, hyaluronic acid (HA) functionalized extracellular vesicles (EVs) are generated as natural vehicles to efficiently deliver doxorubicin (DOX) and reverse MDR. The EVs isolated from noncancerous HEK293T cells (hEVs) reduce P-glycoprotein (P-gp) expression in drug resistant MCF7/ADR cells. To acquire tumor-targeting capability, hEVs are modified with lipidomimetic chains-grafted HA (lipHA) by a simple incubation. Owing to CD44-mediated cancer-specific targeting and P-gp suppressive capability, the HA-functionalized hEVs (lipHA-hEVs) remarkably promote the intracellular DOX accumulation in drug resistant breast cancer cells. In preclinical MDR tumor models, lipHA-hEVs deeply penetrate into tumor tissue and effectively transport DOX into tumor local, while eliminating DOX's systemic toxicity. Importantly, DOX@lipHA-hEVs inhibited MDR tumor growth by 89% and extend animal survival time by approximately 50%. Thus, our engineered tumor-targeting hEVs are promising natural carriers for overcoming cancer MDR.
Insights
Engineered extracellular vesicles (EVs) loaded with doxorubicin (DOX) target tumors and overcome multidrug resistance (MDR) in cancer. This natural nanocarrier approach enhances drug delivery and reduces toxicity, showing significant tumor growth inhibition.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Research
Background:
- Multidrug resistance (MDR) significantly limits chemotherapy efficacy.
- Existing nanocarriers face challenges like complex fabrication, toxicity, and immunogenicity.
- Extracellular vesicles (EVs) offer potential as natural drug delivery systems.
Purpose of the Study:
- To develop hyaluronic acid (HA)-functionalized EVs (lipHA-EVs) for targeted delivery of doxorubicin (DOX) to MDR cancer cells.
- To evaluate the efficacy of lipHA-EVs in overcoming MDR and reducing chemotherapy-related toxicity.
- To assess the potential of lipHA-EVs as a clinical cancer treatment strategy.
Main Methods:
- Isolation of EVs from HEK293T cells (hEVs).
- Functionalization of hEVs with lipidomimetic chains-grafted HA (lipHA) for CD44-mediated targeting.
- Loading of DOX into lipHA-EVs (DOX@lipHA-EVs).
- In vitro assessment of P-glycoprotein (P-gp) expression reduction and intracellular DOX accumulation in drug-resistant MCF7/ADR cells.
- In vivo evaluation in preclinical MDR tumor models.
Main Results:
- lipHA-hEVs reduced P-gp expression in drug-resistant cells.
- lipHA-hEVs enhanced intracellular DOX accumulation via CD44-mediated targeting.
- DOX@lipHA-EVs demonstrated deep tumor penetration and localized DOX delivery.
- Treatment with DOX@lipHA-EVs inhibited MDR tumor growth by 89% and extended survival by ~50%.
- Reduced systemic toxicity of DOX was observed.
Conclusions:
- Engineered HA-functionalized EVs serve as effective natural carriers for overcoming MDR.
- This approach shows promise for improving cancer chemotherapy by enhancing drug delivery and reducing side effects.
- lipHA-EVs represent a potential next-generation nanomedicine for MDR cancer treatment.
Related Concept Videos
10:13Micropatterned Surfaces to Study Hyaluronic Acid Interactions with Cancer Cells
13:45Evaluation of Extracellular Vesicle Function During Malaria Infection
04:16Platelet-Derived Extracellular Vesicle Functionalization of Ti Implants
08:35Hyaluronic-Acid Based Hydrogels for 3-Dimensional Culture of Patient-Derived Glioblastoma Cells
12:01Quantification and Size-profiling of Extracellular Vesicles Using Tunable Resistive Pulse Sensing
03:28Functional Chemoresistance Characterization: A Method to Evaluate Drug Resistance in Cancer Cells Using Clonogenic Assay