紫杉醇纳米制剂研发现状及其在胆道恶性肿瘤的应用进展
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1.华中科技大学同济医学院附属协和医院 肝胆外科,湖北 武汉430022;2.华中科技大学同济医学院附属协和医院 协和中心实验室,湖北 武汉430022

作者简介:

李卓霞,华中科技大学同济医学院附属协和医院硕士研究生,主要从事肝胆恶性肿瘤基础和临床方面的研究。

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国家自然科学基金资助项目(82172754,81874208)。


Current development of paclitaxel nanoformulations and its application progress in biliary tract cancer
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1.Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China;2.Union Hospital Central Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China

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    摘要:

    胆管癌是一种上皮源性的恶性肿瘤,根治性外科手术是首选治疗方案,但是大多数患者初诊时已处于中晚期,丧失手术切除机会,只能采用其他非手术治疗方案。晚期胆管癌的标准一线化疗方案为吉西他滨联合顺铂,但是该方案的中位总生存期仅为11.7个月,且会出现中性粒细胞减少症、血小板减少、疲劳和贫血等不良反应。有Ⅱ期临床研究展现了紫杉醇(PTX)在改善晚期不可切除胆管癌的潜力,因此开启了PTX在治疗晚期胆管癌的新应用。PTX主要通过调控微管蛋白解聚而诱导肿瘤细胞凋亡,疗效显著,但因其溶解性差和毒副作用大而限制了临床应用。随着各种新型纳米载体的出现,PTX毒性和溶解度得到了极大改善,且已有产品转化应用于临床实践。有研究证实,PTX纳米制剂联合化疗、靶向治疗或者免疫检查点抑制剂用于胆道恶性肿瘤的综合治疗,其疗效优于临床常用化疗方案,展现出巨大的临床价值。本文总结了PTX的药理特性和应用壁垒,纳米制剂的研发现状,以及在胆道恶性肿瘤的应用进展,并提出了PTX纳米制剂的研发方向和应用前景。

    Abstract:

    Cholangiocarcinoma is an epithelial-origin malignancy for which radical surgical resection is the preferred treatment option. However, most patients are diagnosed at an advanced stage, have already lost the opportunity for surgical removal and are limited to other non-surgical treatments. The standard first-line chemotherapy for advanced cholangiocarcinoma is gemcitabine combined with cisplatin, but this regimen offers a median overall survival of only 11.7 months and is associated with adverse reactions such as neutropenia, thrombocytopenia, fatigue, and anemia. A phase Ⅱ clinical study has demonstrated the potential of paclitaxel (PTX) in improving outcomes for advanced unresectable cholangiocarcinoma, thereby opening up new a application for PTX in the treatment of advanced cholangiocarcinoma. PTX primarily induces tumor cell apoptosis by regulating microtubule depolymerization, showing significant efficacy. However, its poor solubility and high toxicity have limited its clinical application. With the emergence of various novel nanocarriers, the toxicity and solubility of PTX have been greatly improved, and some products have been translated into clinical practice. Studies have confirmed that PTX nanoformulations combined with chemotherapy, targeted therapy, or immune checkpoint inhibitors offer superior efficacy in treating biliary malignancies compared to standard chemotherapy regimens, demonstrating significant clinical value. This paper summarizes the pharmacological properties and application barriers of PTX, the current status of research and development of its nanoformulations, and the progress in its application in biliary malignancies. It also proposes future research directions and potential applications for PTX nanoformulations.

    图1 PTX的化学结构式及其抗癌作用的主要分子机制 A:化学结构式;B:抗癌作用的主要分子机制Fig.1 The chemical structure of PTX and its main molecular mechanisms of anticancer activity A: Chemical structure; B: Main molecular mechanisms of anticancer activity
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李卓霞,瞿勇,许依婷,李民.紫杉醇纳米制剂研发现状及其在胆道恶性肿瘤的应用进展[J].中国普通外科杂志,2024,33(8):1311-1319.
DOI:10.7659/j. issn.1005-6947.2024.08.012

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  • 收稿日期:2024-06-05
  • 最后修改日期:2024-07-08
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  • 在线发布日期: 2024-09-05