5-氟尿嘧啶（5-FU）已成为近几十年来最广泛使用的抗代谢化疗药物之一，用于治疗各种类型的癌症。它被认为是转移性结直肠癌患者的标准一线治疗。不幸的是，传统的5-FU化疗存在许多局限性，例如半衰期短、生物利用度低和细胞毒性高，同时影响肿瘤组织和健康组织。为了克服5-FU的缺点并增强其对结直肠癌的治疗效果，许多研究集中在设计新的递送系统以成功地将5-FU递送至肿瘤部位。脂质体作为多种​​化疗药物广为接受的纳米载体而受到关注。这些两亲性球形囊泡由一个或多个磷脂双层组成，除了具有生物降解性、生物相容性、低毒性和非免疫原性等独特特性外，还有望用于疏水性和亲水性成分的药物递送。脂质体的最新进展主要集中在化学和结构修饰上，以特异性靶向和激活针对肿瘤附近癌症的治疗作用。本综述全面概述了内部刺激响应性脂质体（例如通过酶或 pH 值激活的脂质体）和外部刺激响应性脂质体（例如通过施加磁场、光或温度变化激活的脂质体）。结直肠癌治疗中 5-FU 的位点特异性递送，以及这些智能递送脂质体在结直肠癌中的未来前景。此外，这篇综述重点强调了文献中关于各种类型的刺激响应脂质体制剂的最新创新，这些制剂设计用于外源性或​​内源性，并且在将 5-FU 递送到结直肠癌部位方面具有巨大潜力。

5-Fluorouracil (5-FU) has become one of the most widely employed antimetabolite chemotherapeutic agents in recent decades to treat various types of cancer. It is considered the standard first-line treatment for patients with metastatic colorectal cancer. Unfortunately, traditional chemotherapy with 5-FU presents many limitations, such as a short half-life, a low bioavailability, and a high cytotoxicity, affecting both tumor tissue and healthy tissue. In order to overcome the drawbacks of 5-FU and enhance its therapeutic effectiveness against colorectal cancer, many studies have focused on designing new delivery systems to successfully deliver 5-FU to tumor sites. Liposomes have gained attention as a well-accepted nanocarrier for several chemotherapeutic agents. These amphipathic spherical vesicles consist of one or more phospholipid bilayers, showing promise for the drug delivery of both hydrophobic and hydrophilic components in addition to distinctive properties, such as biodegradability, biocompatibility, a low toxicity, and non-immunogenicity. Recent progress in liposomes has mainly focused on chemical and structural modifications to specifically target and activate therapeutic actions against cancer within the proximity of tumors. This review provides a comprehensive overview of both internal-stimuli-responsive liposomes, such as those activated by enzymes or pH, and external-stimuli-responsive liposomes, such as those activated by the application of a magnetic field, light, or temperature variations, for the site-specific delivery of 5-FU in colorectal cancer therapy, along with the future perspectives of these smart-delivery liposomes in colorectal cancer. In addition, this review critically highlights recent innovations in the literature on various types of stimuli-responsive liposomal formulations designed to be applied either exogenously or endogenously and that have great potential in delivering 5-FU to colorectal cancer sites.