Meng Chen, Yi Xue, Duan Meitao, Mahal Ahmed, Zhang Zhiqiang, Ren Jungang, Chen Ming, Yang Lin, Xu Moxun, Obaidullah Ahmad J, Song Linwei, Li Shuxian, Wang Chen
College of Pharmacy, Jiamusi University, Jiamusi, China.
Key Laboratory of Functional and Clinical Translational Medicine, Fujian Province University, Xiamen Medical College, Xiamen, China.
Front Pharmacol. 2025 May 30;16:1587560. doi: 10.3389/fphar.2025.1587560. eCollection 2025.
Nanoscale vesicles have emerged as promising biocompatible vehicles for precision drug delivery, owing to their inherent therapeutic properties and versatile structural configurations. This study introduces an innovative biomanufacturing strategy utilizing curcumin-extracted nanovesicles (TNVs) conjugated with a cancer-selective peptide and encapsulated with doxorubicin to optimize therapeutic outcomes in colorectal malignancies. TNVs were purified through refined ultracentrifugation protocols, demonstrating uniform saucer-shaped morphology with an average size of 162.42 ± 3.67 nm and stable bilayer architecture dominated by triglyceride (30%) and ceramide (11.8%) constituents. Peptide-mediated surface functionalization substantially improved intracellular internalization efficiency in HCT-116 colon carcinoma models. The engineered TNV-P-D formulation exhibited potent tumoricidal activity (IC = 54.8 μg/ mL), outperforming both unbound doxorubicin (IC = 795.2 ng/mL) and nonfunctionalized TNV-DOX counterparts (IC = 129.7 μg/mL). Cell cycle profiling revealed G1-phase blockade (91.3% G1-phase occupancy), corroborating the platform's proliferation-inhibiting capacity. In murine CT26. WT xenograft models, TNV-P-D administration achieved significant tumor regression (65% volume reduction, p< 0.001) while preserving hepatobiliary function and demonstrating negligible multiorgan toxicity. These results position peptide-augmented phytovesicles as a multifunctional therapeutic system capable of dual-action tumor targeting and systemic toxicity mitigation in colorectal oncology.
纳米级囊泡因其固有的治疗特性和多样的结构构型,已成为用于精准药物递送的有前景的生物相容性载体。本研究引入了一种创新的生物制造策略,利用与癌症选择性肽缀合并包裹阿霉素的姜黄素提取纳米囊泡(TNVs),以优化结直肠癌的治疗效果。通过精细的超速离心方案纯化TNVs,其呈现出均匀的碟形形态,平均尺寸为162.42±3.67nm,具有以甘油三酯(30%)和神经酰胺(11.8%)成分为主的稳定双层结构。肽介导的表面功能化显著提高了HCT-116结肠癌模型中的细胞内内化效率。工程化的TNV-P-D制剂表现出强大的杀肿瘤活性(IC = 54.8μg/mL),优于游离阿霉素(IC = 795.2ng/mL)和未功能化的TNV-DOX对应物(IC = 129.7μg/mL)。细胞周期分析显示G1期阻滞(G1期占有率为91.3%),证实了该平台的增殖抑制能力。在小鼠CT26.WT异种移植模型中,给予TNV-P-D可实现显著的肿瘤消退(体积减少65%,p<0.001),同时保留肝胆功能并显示出可忽略不计的多器官毒性。这些结果将肽增强的植物囊泡定位为一种多功能治疗系统,能够在结直肠癌治疗中实现双作用肿瘤靶向和减轻全身毒性。
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