关键词: Antitumor activity Balb/c mice Capecitabine delivery Carbohydrate-based nanoparticles Colon cancer Tumor targeting

Mesh : Animals Chitosan / chemistry Colonic Neoplasms / drug therapy pathology Starch / chemistry Solanum tuberosum / chemistry Capecitabine / administration & dosage pharmacology Humans Mice, Inbred BALB C Mice Nanoparticles / chemistry HT29 Cells Antimetabolites, Antineoplastic / administration & dosage pharmacology chemistry Drug Liberation Drug Carriers / chemistry Apoptosis / drug effects Drug Delivery Systems / methods Cell Proliferation / drug effects Male

来  源:   DOI:10.1016/j.ejpb.2024.114328

Abstract:
Aggressive colon cancer treatment poses significant challenges. This study investigates the potential of innovative carbohydrate-based nanoparticles for targeted Capecitabine (CTB) delivery. CTB nanoparticles were synthesized by conjugating CTB with potato starch and chitosan using ultrasonication, hydrolysis, and ionotropic gelation. Characterization included drug loading, rheology, Surface-Enhanced Raman Spectroscopy (SERS), Fourier-Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), and Thermogravimetric Analysis (TGA). In vitro and in vivo antitumor activity was evaluated using HT-29 cells and N, N-dimethylhydrazine-induced Balb/c mice, respectively. Cellular assays assessed angiogenesis, migration, proliferation, and apoptosis. Nanoparticles exhibited a mean size of 245 nm, positive zeta potential (+30 mV), high loading efficacy (76 %), and sustained drug release (92 % over 100 h). CTB-loaded nanoparticles displayed superior colon histology, reduced tumour scores, and inhibited VEGD and CD31 expression compared to free CTB. Cellular assays confirmed significant antitumor effects, including reduced tube formation, migration, and proliferation, and increased apoptosis. This study demonstrates the promise of CTB-loaded potato starch-chitosan nanoparticles for aggressive colon cancer treatment. These findings highlight the potential of these nanoparticles for further evaluation in diverse cancer models.
摘要:
侵袭性结肠癌治疗提出了重大挑战。这项研究调查了基于碳水化合物的创新纳米颗粒用于靶向卡培他滨(CTB)递送的潜力。CTB纳米颗粒通过CTB与马铃薯淀粉和壳聚糖结合使用超声波合成,水解,和离子凝胶化。表征包括载药量,流变学,表面增强拉曼光谱(SERS),傅里叶变换红外光谱(FTIR),差示扫描量热法(DSC),X射线衍射(XRD)和热重分析(TGA)。使用HT-29细胞和N,N-二甲基肼诱导的Balb/c小鼠,分别。细胞试验评估血管生成,迁移,扩散,和凋亡。纳米粒子表现出245nm的平均尺寸,正ζ电位(+30mV),高负荷效率(76%),和持续药物释放(92%超过100小时)。载有CTB的纳米颗粒显示上结肠组织学,降低肿瘤评分,与游离CTB相比,抑制VEGD和CD31表达。细胞试验证实了显著的抗肿瘤作用,包括减少的管形成,迁移,和扩散,和增加细胞凋亡。这项研究证明了负载CTB的马铃薯淀粉-壳聚糖纳米颗粒用于侵袭性结肠癌治疗的前景。这些发现强调了这些纳米颗粒在不同癌症模型中进一步评估的潜力。
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