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Aptamer Circuit-Engineered Bio-Nanovesicles With Self-Promoted Tumor-Targeting Loop for Efficient Immunogenic
Shuxuan Shao1, Cao Zhang1, Wei Du2
1Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing, FuRong Laboratory, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan, China.
This study introduces a novel aptamer-guided extracellular vesicle (EV) system for targeted chemotherapy. The system enhances drug delivery to tumors by amplifying targeting signals and inducing immunogenic cell death for improved cancer treatment.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Targeted drug delivery is crucial for effective chemotherapy, minimizing side effects.
- Extracellular vesicles (EVs) show promise as drug carriers but lack sufficient tumor-targeting ability.
- Developing advanced strategies to enhance EV tumor specificity is essential.
Purpose of the Study:
- To design an aptamer-based cascade recognition system to improve EV tumor targeting.
- To engineer a self-promoted targeting loop to amplify drug delivery to cancer cells.
- To evaluate the therapeutic efficacy of this enhanced EV system in cancer treatment.
Main Methods:
- Constructed an aptamer circuit for sequential signal transduction and cascade recognition.
- Utilized Doxorubicin Hydrochloride (DOX)-loaded EVs for drug delivery.
- Investigated the role of PDL1 marker upregulation in tumor targeting.
- Assessed the induction of immunogenic cell death (ICD) and anti-tumor immune response.
Main Results:
- The aptamer circuit enabled preferential binding of EVs to cancer cells over non-cancerous cells.
- DOX release triggered a self-promoted targeting loop, upregulating PDL1 and enhancing tumor accumulation.
- The engineered EVs successfully induced ICD and stimulated an anti-tumor immune response.
- Improved therapeutic outcomes were observed with the vesicle-based drug carrier.
Conclusions:
- A self-promoted tumor-targeting strategy for EV-based carriers was successfully developed.
- Coupling cascade recognition and a tumor-targeting loop significantly enhances therapeutic effects.
- This approach offers a promising strategy for immunogenic chemotherapy and cancer treatment.
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