Yang Juanjuan, Wang Xiaojin, Wang Bingshun, Park Kinam, Wooley Karen, Zhang Shiyi
School of Biomedical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China.
Department of Biostatistics, Clinical Research Institute, Shanghai Jiao Tong University School of Medicine, 227 South Chongqing Road, Shanghai 200025, PR China.
Adv Drug Deliv Rev. 2022 Nov;190:114525. doi: 10.1016/j.addr.2022.114525. Epub 2022 Sep 11.
Nanomedicines for cancer treatment have been studied extensively over the last few decades. Yet, only five anticancer nanomedicines have received approvals from the United States Food and Drug Administration (FDA) for treating solid tumors. This drastic mismatch between effort and return calls into question the basic understanding of this field. Various viewpoints on nanomedicines have been presented regarding their potentials and inefficiencies. However, the underlying logics of nanomedicine research and its inadequate translation to the successful use in the clinic have not been thoroughly examined. Tumor-targeted drug delivery was used to understand the shortfalls of the nanomedicine field in general. The concept of tumor-targeted drug delivery by nanomedicine has been based on two conjectures: (i) increased drug delivery to tumors provides better efficacy, and (ii) decreased drug delivery to healthy organs results in fewer side effects. The clinical evidence gathered from the literature indicates that nanomedicines bearing classic chemotherapeutic drugs, such as Dox, cis-Pt, CPT and PTX, have already reached the maximum drug delivery limit to solid tumors in humans. Still, the anticancer efficacy and safety remain unchanged despite the increased tumor accumulation. Thus, it is understandable to see few nanomedicine-based formulations approved by the FDA. The examination of FDA-approved nanomedicine formulations indicates that their approvals were not based on the improved delivery to tumors but mostly on changes in dose-limiting toxicity unique to each drug. This comprehensive analysis of the fundamentals of anticancer nanomedicines is designed to provide an accurate picture of the field's underlying false conjectures, hopefully, thereby accelerating the future clinical translations of many formulations under research.
在过去几十年里，用于癌症治疗的纳米药物得到了广泛研究。然而，只有五种抗癌纳米药物获得了美国食品药品监督管理局（FDA）批准用于治疗实体瘤。这种努力与回报之间的巨大差距让人质疑该领域的基本认知。关于纳米药物的潜力和低效性，已经提出了各种观点。然而，纳米药物研究的潜在逻辑及其在临床成功应用方面的不足尚未得到充分审视。为了全面了解纳米药物领域的不足，我们以肿瘤靶向给药为例进行分析。纳米药物肿瘤靶向给药的概念基于两个推测：（i）增加药物向肿瘤的递送可提高疗效，（ii）减少药物向健康器官的递送可减少副作用。从文献中收集的临床证据表明，携带经典化疗药物（如阿霉素、顺铂、喜树碱和紫杉醇）的纳米药物，在人体中已经达到了向实体瘤递送药物的最大极限。尽管肿瘤内药物蓄积增加，但其抗癌疗效和安全性仍未改变。因此，FDA批准的基于纳米药物的制剂寥寥无几也就不足为奇了。对FDA批准的纳米药物制剂的审查表明，其获批并非基于向肿瘤递送的改善，而是主要基于每种药物独特的剂量限制性毒性的变化。对抗癌纳米药物基本原理的全面分析旨在准确呈现该领域潜在的错误推测，有望借此加速许多正在研究的制剂未来的临床转化。
