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Light-activated photosensitizer/quercetin co-loaded extracellular vesicles for precise oral squamous cell carcinoma
Qian Liu1, Dandan Jiang2, Shasha Zhang1
1Department of Pathology, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215002, China.
Abstract:
Oral squamous cell carcinoma (OSCC) is the most common subtype of head and neck malignancies, characterized by a five-year survival rate that remains persistently below 50%, indicative of limited progress in therapeutic interventions. There is an urgent imperative to develop innovative therapeutic strategies, warranting the investigation of advanced treatment modalities. Nanocarriers offer a promising avenue by significantly enhancing drug properties and pharmacokinetics. Extracellular vesicles (EVs) are naturally occurring nanocarriers produced by cells and have become a focal point in drug delivery research. Quercetin, one of the most abundant dietary flavonoids, exhibits potent anticancer effects. However, its pharmaceutical application is hampered by poor water solubility, instability under physiological conditions, and low bioavailability. To overcome these obstacles, we propose using bio-derived EVs as carriers to co-encapsulate quercetin with the photosensitizer chlorin e6. This strategy leverages the intrinsic targeting capabilities of EVs for precise drug delivery to tumors, along with light-activated drug release, enabling rapid quercetin release under near-infrared light, effectively inhibiting cellular proliferation and inducing apoptosis in tumor cells. In vivo studies demonstrated that drug-loaded EVs exhibited robust tumor-targeting efficacy, resulting in effective and selective tumor ablation upon photoactivation in mice bearing subcutaneous MOC2 tumors.
Insights
This study introduces extracellular vesicles (EVs) as nanocarriers for quercetin and chlorin e6, enhancing oral squamous cell carcinoma (OSCC) treatment. Light-activated EVs selectively target and destroy OSCC tumors, improving therapeutic outcomes.
Area of Science:
- Oncology
- Nanotechnology
- Pharmacology
Background:
- Oral squamous cell carcinoma (OSCC) has a poor prognosis, necessitating novel therapeutic approaches.
- Dietary flavonoids like quercetin show anticancer potential but face bioavailability challenges.
- Extracellular vesicles (EVs) are natural nanocarriers with potential for targeted drug delivery.
Purpose of the Study:
- To develop an innovative therapeutic strategy for OSCC using bio-derived EVs.
- To co-encapsulate quercetin and chlorin e6 within EVs for enhanced drug delivery and efficacy.
- To investigate the potential of light-activated quercetin release for tumor ablation.
Main Methods:
- Bio-derived extracellular vesicles (EVs) were utilized as nanocarriers.
- Quercetin and the photosensitizer chlorin e6 were co-encapsulated into EVs.
- In vitro and in vivo studies were conducted using OSCC models (MOC2 tumors in mice).
- Near-infrared light was used for photoactivation and drug release.
Main Results:
- Drug-loaded EVs demonstrated effective tumor-targeting capabilities in vivo.
- Photoactivation with near-infrared light triggered rapid quercetin release.
- Selective tumor ablation was achieved in mice bearing subcutaneous MOC2 tumors.
- The treatment inhibited cellular proliferation and induced apoptosis in tumor cells.
Conclusions:
- Co-encapsulation of quercetin and chlorin e6 in EVs offers a promising strategy for OSCC treatment.
- EVs facilitate targeted drug delivery and light-activated release, enhancing therapeutic efficacy.
- This approach shows potential for selective tumor ablation and improved outcomes in OSCC management.
