Gaurav Isha, Thakur Abhimanyu, Zhang Kui, Thakur Sudha, Hu Xin, Xu Zhijie, Kumar Gaurav, Jaganathan Ravindran, Iyaswamy Ashok, Li Min, Zhang Ge, Yang Zhijun
School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.
Department of Pharmacology, Delhi Pharmaceutical Sciences & Research University (DPSRU), New Delhi 110017, India.
Nanomaterials (Basel). 2024 Oct 17;14(20):1669. doi: 10.3390/nano14201669.
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.
肺癌是主要的癌症类型之一，其治疗面临诸多挑战，包括缺乏特异性以及对健康细胞的损害。基于纳米颗粒的药物递送系统（NDDSs）在克服这些挑战方面显示出前景。虽然传统的NDDSs存在诸如免疫反应和被网状内皮系统（RES）捕获等缺点，但细胞外囊泡（EVs）提供了一种潜在的解决方案。EVs是细胞自然释放的，无需表面修饰即可避开RES，并且对健康细胞的毒性最小。这使其成为开发肺癌靶向药物递送系统的有希望的候选者。从血管内皮细胞分离的EVs，如人脐静脉内皮细胞衍生的EVs（HUVEC-EVs），在肺癌小鼠模型中已显示出抗血管生成活性；因此，在本研究中，选择HUVEC-EVs作为药物递送载体。为了实现肺癌特异性靶向，通过后插入技术将GE11肽修饰到HUVEC-EVs上（GE11-HUVEC-EVs），以靶向在肺癌细胞表面过度表达的表皮生长因子受体（EGFR）。将长春瑞滨负载到GE11-HUVEC-EVs上（GE11-HUVEC-EVs-Vin），然后在体外和体内肺癌模型中进行表征和评估。此外，我们检测了编码P-糖蛋白的ABCB1的结合亲和力，P-糖蛋白通过药物外排在化疗耐药中起关键作用。我们的结果表明，GE11-HUVEC-EVs-Vin对肺癌细胞和小鼠模型有效显示出杀肿瘤作用。
