Active Pharmaceutical Ingredient (API) Section, Centre of Product Registration, National Pharmaceutical Regulatory Agency (NPRA), Lot 36, Jalan Universiti, 46200 Petaling Jaya, Malaysia.
Integrative Medicine Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, 13200 Bertam, Penang, Malaysia.
Int J Mol Sci. 2018 Jun 11;19(6):1725. doi: 10.3390/ijms19061725.
In the field of medicine, nanomaterials, especially those derived using the green method, offer promise as anti-cancer agents and drug carriers. However, the biosafety of metallic nanoparticles used as anti-cancer agents remains a concern. The goal of this systematic review was to compare the cytotoxicity of different plant-mediated syntheses of metallic nanoparticles based on their potency, therapeutic index, and cancer cell type susceptibility in the hopes of identifying the most promising anti-cancer agents. A literature search of electronic databases including Science Direct, PubMed, Springer Link, Google Scholar, and ResearchGate, was conducted to obtain research articles. Keywords such as biosynthesis, plant synthesis, plant-mediated, metallic nanoparticle, cytotoxicity, and anticancer were used in the literature search. All types of research materials that met the inclusion criteria were included in the study regardless of whether the results were positive, negative, or null. The therapeutic index was used as a safety measure for the studied compound of interest. Data from 76 selected articles were extracted and synthesised. Seventy-two studies reported that the cytotoxicity of plant-mediated synthesis of metallic nanoparticles was time and/or dose-dependent. Biosynthesised silver nanoparticles demonstrated higher cytotoxicity potency compared to gold nanoparticles synthesised by the same plants (, , and ) irrespective of the cancer cell type tested. This review also identified a correlation between the nanoparticle size and morphology with the potency of cytotoxicity. Cytotoxicity was found to be inversely proportional to nanoparticle size. The plant-mediated syntheses of metallic nanoparticles were predominantly spherical or quasi-spherical, with the median lethal dose of 1⁻20 µg/mL. Nanoparticles with other shapes (triangular, hexagonal, and rods) were less potent. Metallic nanoparticles synthesised by , , , , and were acceptably safe as anti-cancer agents, as they had a therapeutic index of >2.0 when tested on both cancer cells and normal human cells. Most plant-mediated syntheses of metallic nanoparticles were found to be cytotoxic, although some were non-cytotoxic. The results from this study suggest a focus on a selected list of potential anti-cancer agents for further investigations of their pharmacodynamic/toxicodynamic and pharmacokinetic/toxicokinetic actions with the goal of reducing the Global Burden of Diseases and the second leading cause of mortality.
在医学领域，纳米材料，特别是采用绿色方法制备的纳米材料，作为抗癌药物和药物载体具有广阔的应用前景。然而，作为抗癌药物的金属纳米粒子的生物安全性仍然令人担忧。本系统评价的目的是比较不同植物介导合成的金属纳米粒子的细胞毒性，根据其效力、治疗指数和癌细胞类型易感性，以期确定最有前途的抗癌药物。通过电子数据库（包括 Science Direct、PubMed、Springer Link、Google Scholar 和 ResearchGate）进行文献检索，以获取研究文章。文献检索中使用了生物合成、植物合成、植物介导、金属纳米粒子、细胞毒性和抗癌等关键词。所有符合纳入标准的研究材料，无论结果是阳性、阴性还是无效，都包括在研究中。治疗指数被用作所研究的化合物的安全性指标。从 76 篇选定的文章中提取和综合了数据。72 项研究报告称，植物介导合成的金属纳米粒子的细胞毒性具有时间和/或剂量依赖性。与用相同植物合成的金纳米粒子相比，生物合成的银纳米粒子表现出更高的细胞毒性效力（[14]、[15]和[16]），而与所测试的癌细胞类型无关。本综述还确定了纳米粒子的大小和形态与细胞毒性效力之间的相关性。细胞毒性与纳米粒子的大小成反比。植物介导的金属纳米粒子合成通常为球形或准球形，中位致死剂量为 1⁻20 µg/mL。具有其他形状（三角形、六边形和棒状）的纳米粒子则效力较低。用[17]、[18]、[19]、[20]和[21]合成的金属纳米粒子被认为是安全的抗癌药物，因为它们在癌细胞和正常人类细胞上的治疗指数均>2.0。大多数植物介导的金属纳米粒子合成都具有细胞毒性，但也有一些是非细胞毒性的。本研究结果表明，应重点关注一组有潜力的抗癌药物，进一步研究其药效/毒性动力学和药代动力学/毒性动力学作用，以期降低全球疾病负担和第二大死亡原因。
