School of Pharmaceutical Sciences, Sao Paulo State University (UNESP), Rodovia Araraquara-Jau/ Km 01, Campos Ville, 14800-903 - Araraquara, SP, Brazil.
Curr Med Chem. 2021;28(26):5411-5430. doi: 10.2174/0929867328666210319144347.
Pancreatic Ductal Adenocarcinoma (PDA) is a highly metastatic tumor, and the liver is its first target, which restricts the use of medications. PDA is considered one of the most aggressive types of cancer in the world, with an extremely short survival time, depending on the stage of diagnosis. In non-surgical cases, chemotherapy alternatives are only effective in 40% to 60% of patients. The low efficiency of treatments occurs mainly due to the complex microenvironment in PDA, leading to chemoresistance to treatments and making it difficult to reach the affected tissue. A very important histological characteristic of PDA is the extremely dense stroma, which leads to low vascularization of tumor tissue. Consequently, the stroma environment causes less drug accumulation in tumor cells, even of selective and/or targeted drugs. Overcoming the stroma's microenvironment is a major challenge for therapies. Moreover, specific genes lead to direct chemoresistance in PDA due to their high progression. In this scenario, nanotechnology appears as an alternative to overcome these clinical challenges concerning two distinct ways: acting on the stroma or/and acting directly on the pancreatic tumor cells. Thus, this review aimed to highlight advances in the application of nanotechnology aiming to open up new landscapes against PDA. There are a huge number of nanoparticles carrying drugs in preclinical and clinical trials for the effective treatment of PDA. These works have been discussed, and based on the current scenario, the future prospects for an efficient treatment of PDA have been proposed.
胰腺导管腺癌（PDA）是一种高度转移性肿瘤，肝脏是其首选转移部位，这限制了药物的应用。PDA 被认为是世界上侵袭性最强的癌症之一，其生存时间极短，取决于诊断阶段。在非手术病例中，化疗替代方案仅对 40%至 60%的患者有效。治疗效率低下主要是由于 PDA 复杂的微环境导致对治疗的耐药性，难以到达受影响的组织。PDA 的一个非常重要的组织学特征是极其密集的基质，导致肿瘤组织的血管化程度低。因此，基质环境导致肿瘤细胞中药物积累较少，即使是选择性和/或靶向药物也是如此。克服基质的微环境是治疗的主要挑战。此外，由于其高进展性，特定基因导致 PDA 直接产生化疗耐药性。在这种情况下，纳米技术作为一种克服这些临床挑战的替代方法出现，有两种不同的作用方式：作用于基质或/和直接作用于胰腺肿瘤细胞。因此，本综述旨在强调纳米技术应用方面的进展，以期为 PDA 开辟新的治疗前景。有大量载药的纳米颗粒正在进行临床前和临床试验，以有效治疗 PDA。这些工作已经被讨论过了，并且根据目前的情况，提出了对 PDA 进行有效治疗的未来前景。
