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Peptide-Conjugated Vascular Endothelial Extracellular Vesicles Encapsulating Vinorelbine for Lung Cancer Targeted
Isha Gaurav1, Abhimanyu Thakur2,3, Kui Zhang4
1School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.
Abstract:
Lung cancer is one of the major cancer types and poses challenges in its treatment, including lack of specificity and harm to healthy cells. Nanoparticle-based drug delivery systems (NDDSs) show promise in overcoming these challenges. While conventional NDDSs have drawbacks, such as immune response and capture by the reticuloendothelial system (RES), extracellular vesicles (EVs) present a potential solution. EVs, which are naturally released from cells, can evade the RES without surface modification and with minimal toxicity to healthy cells. This makes them a promising candidate for developing a lung-cancer-targeting drug delivery system. EVs isolated from vascular endothelial cells, such as human umbilical endothelial-cell-derived EVs (HUVEC-EVs), have shown anti-angiogenic activity in a lung cancer mouse model; therefore, in this study, HUVEC-EVs were chosen as a carrier for drug delivery. To achieve lung-cancer-specific targeting, HUVEC-EVs were engineered to be decorated with GE11 peptides (GE11-HUVEC-EVs) via a postinsertional technique to target the epidermal growth factor receptor (EGFR) that is overexpressed on the surface of lung cancer cells. The GE11-HUVEC-EVs were loaded with vinorelbine (GE11-HUVEC-EVs-Vin), and then characterized and evaluated in in vitro and in vivo lung cancer models. Further, we examined the binding affinity of ABCB1, encoding P-glycoprotein, which plays a crucial role in chemoresistance via the efflux of the drug. Our results indicate that GE11-HUVEC-EVs-Vin effectively showed tumoricidal effects against cell and mouse models of lung cancer.
Insights
Engineered extracellular vesicles (EVs) carrying lung cancer drugs target tumors effectively. This novel nanoparticle drug delivery system (NDDS) shows promise for improved lung cancer treatment with reduced side effects.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Lung cancer treatment faces challenges with specificity and healthy cell toxicity.
- Nanoparticle-based drug delivery systems (NDDSs) offer potential solutions but have drawbacks like immune response.
- Extracellular vesicles (EVs) are natural nanoparticles that evade immune detection and offer a safer alternative.
Purpose of the Study:
- To develop a lung-cancer-targeting drug delivery system using engineered extracellular vesicles.
- To investigate the efficacy of GE11 peptide-decorated HUVEC-EVs loaded with vinorelbine for lung cancer treatment.
Main Methods:
- Human umbilical endothelial cell-derived EVs (HUVEC-EVs) were engineered with GE11 peptides for EGFR targeting.
- GE11-HUVEC-EVs were loaded with vinorelbine (GE11-HUVEC-EVs-Vin).
- In vitro and in vivo lung cancer models were used to evaluate the drug delivery system's efficacy and binding affinity to ABCB1.
Main Results:
- GE11-HUVEC-EVs-Vin demonstrated effective tumoricidal effects in both cell and mouse models of lung cancer.
- The engineered EVs showed targeted delivery to lung cancer cells overexpressing EGFR.
- The study examined the interaction with ABCB1, a key factor in chemoresistance.
Conclusions:
- Engineered HUVEC-EVs decorated with GE11 peptides represent a promising platform for targeted lung cancer drug delivery.
- This approach may overcome limitations of conventional NDDSs and improve therapeutic outcomes.
- Further research into the interaction with chemoresistance mechanisms like ABCB1 is warranted.
