Samanta Kamalika, Setua Saini, Kumari Sonam, Jaggi Meena, Yallapu Murali M, Chauhan Subhash C
Department of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Department of Immunology and Microbiology, Institute for Cancer Immunotherapy, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78503, USA.
Pharmaceutics. 2019 Nov 4;11(11):574. doi: 10.3390/pharmaceutics11110574.
Pancreatic cancer is one of the deadliest causes of cancer-related death in the United States, with a 5-year overall survival rate of 6 to 8%. These statistics suggest that immediate medical attention is needed. Gemcitabine (GEM) is the gold standard first-line single chemotherapy agent for pancreatic cancer but, after a few months, cells develop chemoresistance. Multiple clinical and experimental investigations have demonstrated that a combination or co-administration of other drugs as chemotherapies with GEM lead to superior therapeutic benefits. However, such combination therapies often induce severe systemic toxicities. Thus, developing strategies to deliver a combination of chemotherapeutic agents more securely to patients is needed. Nanoparticle-mediated delivery can offer to load a cocktail of drugs, increase stability and availability, on-demand and tumor-specific delivery while minimizing chemotherapy-associated adverse effects. This review discusses the available drugs being co-administered with GEM and the limitations associated during the process of co-administration. This review also helps in providing knowledge of the significant number of delivery platforms being used to overcome problems related to gemcitabine-based co-delivery of other chemotherapeutic drugs, thereby focusing on how nanocarriers have been fabricated, considering the modes of action, targeting receptors, pharmacology of chemo drugs incorporated with GEM, and the differences in the physiological environment where the targeting is to be done. This review also documents the focus on novel mucin-targeted nanotechnology which is under development for pancreatic cancer therapy.
胰腺癌是美国癌症相关死亡中最致命的原因之一，其5年总生存率为6%至8%。这些统计数据表明需要立即就医。吉西他滨（GEM）是胰腺癌的金标准一线单一化疗药物，但几个月后，细胞会产生化疗耐药性。多项临床和实验研究表明，将其他药物与GEM联合或共同给药作为化疗可带来更好的治疗效果。然而，这种联合疗法往往会引发严重的全身毒性。因此，需要制定策略，更安全地将化疗药物组合递送给患者。纳米颗粒介导的递送可以提供装载多种药物的组合，提高稳定性和可用性，实现按需和肿瘤特异性递送，同时将化疗相关的不良反应降至最低。本综述讨论了与GEM联合使用的现有药物以及联合给药过程中相关的局限性。本综述还有助于提供有关大量递送平台的知识，这些平台用于克服与基于吉西他滨的其他化疗药物联合递送相关的问题，从而重点关注纳米载体是如何制造的，考虑其作用方式、靶向受体、与GEM联合使用的化疗药物的药理学，以及进行靶向的生理环境的差异。本综述还记录了对正在开发用于胰腺癌治疗的新型粘蛋白靶向纳米技术的关注。
