School of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China.
State Key Laboratory of Southwestern Chinese Medicine Resources, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
Adv Drug Deliv Rev. 2022 Sep;188:114445. doi: 10.1016/j.addr.2022.114445. Epub 2022 Jul 9.
The therapeutic limitations such as insufficient efficacy, drug resistance, metastasis, and undesirable side effects are frequently caused by the long duration monotherapy based on chemotherapeutic drugs. multiple combinational anticancer strategies such as nucleic acids combined with chemotherapeutic agents, chemotherapeutic combinations, chemotherapy and tumor immunotherapy combinations have been embraced, holding great promise to counter these limitations, while still taking including some potential risks. Nowadays, an increasing number of research has manifested the anticancer effects of phytochemicals mediated by modulating cancer cellular events directly as well as the tumor microenvironment. Specifically, these natural compounds exhibited suppression of cancer cell proliferation, apoptosis, migration and invasion of cancer cells, P-glycoprotein inhibition, decreasing vascularization and activation of tumor immunosuppression. Due to the low toxicity and multiple modulation pathways of these phytochemicals, the combination of chemotherapeutic agents with natural compounds acts as a novel approach to cancer therapy to increase the efficiency of cancer treatments as well as reduce the adverse consequences. In order to achieve the maximized combination advantages of small-molecule chemotherapeutic drugs and natural compounds, a variety of functional nano-scaled drug delivery systems, such as liposomes, host-guest supramolecules, supramolecules, dendrimers, micelles and inorganic systems have been developed for dual/multiple drug co-delivery. These co-delivery nanomedicines can improve pharmacokinetic behavior, tumor accumulation capacity, and achieve tumor site-targeting delivery. In that way, the improved antitumor effects through multiple-target therapy and reduced side effects by decreasing dose can be implemented. Here, we present the synergistic anticancer outcomes and the related mechanisms of the combination of phytochemicals with small-molecule anticancer drugs. We also focus on illustrating the design concept, and action mechanisms of nanosystems with co-delivery of drugs to synergistically improve anticancer efficacy. In addition, the challenges and prospects of how these insights can be translated into clinical benefits are discussed.
基于化疗药物的单一疗法，其治疗效果有限、耐药性、转移和不良副作用等问题频繁出现。为了应对这些局限性，目前已采用了多种联合抗癌策略，如核酸与化疗药物联合、化疗联合、化疗与肿瘤免疫治疗联合等，这些策略具有很大的应用前景，但同时也存在一些潜在风险。如今，越来越多的研究表明，植物化学物质通过直接调节肿瘤细胞事件以及肿瘤微环境来发挥抗癌作用。具体而言，这些天然化合物表现出抑制癌细胞增殖、促进癌细胞凋亡、抑制癌细胞迁移和侵袭、抑制 P-糖蛋白、减少血管生成和激活肿瘤免疫抑制等作用。由于这些植物化学物质的毒性低且具有多种调节途径，因此将化疗药物与天然化合物联合使用是一种新型的癌症治疗方法，可以提高癌症治疗的效率，同时减少不良反应。为了实现小分子化疗药物和天然化合物联合的最大化组合优势，开发了各种功能纳米级药物输送系统，如脂质体、主体-客体超分子、超分子、树枝状大分子、胶束和无机系统，用于双重/多重药物共递药。这些共递药纳米药物可以改善药代动力学行为、肿瘤积累能力，并实现肿瘤部位靶向递药。这样，就可以通过多靶点治疗提高抗肿瘤效果，减少副作用（降低剂量）。在此，我们提出了植物化学物质与小分子抗癌药物联合应用的协同抗癌效果及其相关机制。我们还重点介绍了共递药纳米系统的设计概念和作用机制，以协同提高抗癌疗效。此外，还讨论了如何将这些见解转化为临床获益所面临的挑战和前景。
