Tng Danny Jian Hang, Song Peiyi, Hu Rui, Yang Chengbin, Tan Cher Heng, Yong Ken-Tye
School of Electrical and Electronic Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798.
Department of Diagnostic Radiology, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433.
ACS Biomater Sci Eng. 2015 Nov 9;1(11):1055-1066. doi: 10.1021/acsbiomaterials.5b00369. Epub 2015 Sep 24.
As each tumor is unique, treatments should be individualized in terms of their drug formulation and time dependent dosing. In vitro lab-on-a-chip (LOC) drug testing is a viable avenue to individualize treatments. A drug testing platform in the form of a customizable standalone LOC system is proposed for treatment individualization in vitro. The platform was used to individualize the treatment of pancreatic cancer by using PANC-1 and MIA PaCa-2 cell lines cultured on-chip. Using on-chip drug uptake, growth, and migration inhibition assays, the therapeutic effect of various treatment combinations was analyzed. Thereafter, optimized treatments were devised for each cell line. The individualized dosage for MIA PaCa-2 cell line was found to be between 0.05-0.1 μg/μL of doxorubicin (DOX), where the greatest growth and migration inhibition effects were observed. As the PANC-1 cell line showed resistance to DOX only formulations, a multidrug approach was used for individualized treatment. Compared to the DOX only formulations, the individualized treatment produced the same degree of migration inhibition but with 5-10 times lower concentration of DOX, potentially minimizing the side-effects of the treatment. Furthermore, the individualized treatment had an average of 672.4% higher rate of growth inhibition. Finally, a preliminary study showed how a tested formulation from the LOC system can be translated for use by employing a nanoparticle system for controlled delivery, producing similar therapeutic effects. The use of such systems in clinical practice could potentially revolutionize treatment formulation by maximizing the therapeutic effects of existing treatments while minimizing their potential side effects through individualization of treatment.
由于每个肿瘤都是独特的,因此治疗应在药物制剂和时间依赖性给药方面进行个体化。体外芯片实验室(LOC)药物测试是实现治疗个体化的可行途径。本文提出了一种可定制的独立LOC系统形式的药物测试平台,用于体外治疗个体化。该平台通过使用芯片上培养的PANC-1和MIA PaCa-2细胞系,对胰腺癌治疗进行个体化。通过芯片上的药物摄取、生长和迁移抑制试验,分析了各种治疗组合的治疗效果。此后,为每个细胞系设计了优化的治疗方案。发现MIA PaCa-2细胞系的个体化剂量为0.05-0.1μg/μL阿霉素(DOX),在此剂量下观察到最大的生长和迁移抑制效果。由于PANC-1细胞系仅对DOX制剂表现出抗性,因此采用多药方法进行个体化治疗。与仅使用DOX的制剂相比,个体化治疗产生了相同程度的迁移抑制,但DOX浓度降低了5-10倍,从而可能使治疗的副作用最小化。此外,个体化治疗的平均生长抑制率高出672.4%。最后,一项初步研究表明,如何通过采用纳米颗粒系统进行控释来转化LOC系统中测试的制剂以供使用,从而产生相似的治疗效果。在临床实践中使用此类系统可能会彻底改变治疗方案,通过最大化现有治疗的治疗效果,同时通过个体化治疗最小化其潜在副作用。