体外、体内和计算机模拟研究载氧壳聚糖纳米液滴作为潜在药物载体的抗癌效果。

'In Vitro', 'In Vivo' and 'In Silico' Investigation of the Anticancer Effectiveness of Oxygen-Loaded Chitosan-Shelled Nanodroplets as Potential Drug Vector.

机构信息

Dipartimento di Neuroscienze, Università di Torino, Corso Raffaello 30, 10125, Torino, Italy.

Dipartimento di Scienze della Sanità Pubblica e Pediatriche, Università di Torino, Via Santena 5 bis, Torino, 10126, Italy.

出版信息

Pharm Res. 2018 Feb 26;35(4):75. doi: 10.1007/s11095-018-2371-z.

Abstract

PURPOSE

Chitosan-shelled/decafluoropentane-cored oxygen-loaded nanodroplets (OLN) are a new class of nanodevices to effectively deliver anti-cancer drugs to tumoral cells. This study investigated their antitumoral effects 'per se', using a mathematical model validated on experimental data.

METHODS

OLN were prepared and characterized either in vitro or in vivo. TUBO cells, established from a lobular carcinoma of a BALB-neuT mouse, were investigated following 48 h of incubation in the absence/presence of different concentrations of OLN. OLN internalization, cell viability, necrosis, apoptosis, cell cycle and reactive oxygen species (ROS) production were checked as described in the Method section. In vivo tumor growth was evaluated after subcutaneous transplant in BALB/c mice of TUBO cells either without treatment or after 24 h incubation with 10% v/v OLN.

RESULTS

OLN showed sizes of about 350 nm and a positive surface charge (45 mV). Dose-dependent TUBO cell death through ROS-triggered apoptosis following OLN internalization was detected. A mathematical model predicting the effects of OLN uptake was validated on both in vitro and in vivo results.

CONCLUSIONS

Due to their intrinsic toxicity OLN might be considered an adjuvant tool suitable to deliver their therapeutic cargo intracellularly and may be proposed as promising combined delivery system.

摘要

目的

壳聚糖/全氟戊烷核载氧纳米液滴(OLN)是一类新型纳米器件,可有效将抗癌药物递送至肿瘤细胞。本研究使用基于实验数据验证的数学模型,研究了其本身的抗肿瘤作用。

方法

OLN 进行了体外或体内的制备和表征。在不存在/存在不同浓度 OLN 的情况下,将来源于 BALB-neuT 小鼠小叶癌的 TUBO 细胞孵育 48 小时,进行后续研究。如方法部分所述,检查 OLN 内化、细胞活力、坏死、凋亡、细胞周期和活性氧(ROS)产生。将 TUBO 细胞皮下移植到 BALB/c 小鼠中,不进行治疗或在 24 小时内用 10%v/v OLN 孵育后,评估体内肿瘤生长情况。

结果

OLN 粒径约为 350nm,表面带正电荷(45mV)。检测到 ROS 触发凋亡导致 OLN 内化后 TUBO 细胞呈剂量依赖性死亡。预测 OLN 摄取效果的数学模型在体外和体内结果上均得到了验证。

结论

由于其内在毒性,OLN 可被视为一种合适的辅助工具,可将其治疗性货物递送至细胞内,并可作为有前途的联合递药系统进行推广。

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