Pancreatic ductal adenocarcinoma (PDAC) remains a challenging malignancy, mainly due to its resistance to chemotherapy and its complex tumour microenvironment characterised by stromal desmoplasia. There is a need for new strategies to improve the delivery of drugs and therapeutic response. Relevant preclinical tumour models are needed to test potential treatments. This paper compared orthotopic and subcutaneous PDAC tumour models and their suitability for drug delivery studies. A novel aspect was the broad range of tumour properties that were studied, including tumour growth, histopathology, functional vasculature, perfusion, immune cell infiltration, biomechanical characteristics, and especially the extensive analysis of the structure and the orientation of the collagen fibres in the two tumour models. The study unveiled new insights into how these factors impact the uptake of a fluorescent model drug, the macromolecule called 800CW. While the orthotopic model offered a more clinically relevant microenvironment, the subcutaneous model offered advantages for drug delivery studies, primarily due to its reproducibility, and it was characterised by a more efficient drug uptake facilitated by its collagen organisation and well-perfused vasculature. The tumour uptake seemed to be influenced mainly by the structural organisation and the alignment of the collagen fibres and perfusion. Recognising the diverse characteristics of these models and their multifaceted impacts on drug delivery is crucial for designing clinically relevant experiments and improving our understanding of pancreatic cancer biology.
胰腺导管腺癌（PDAC）因其对化疗的耐药性以及以间质纤维化为特征的复杂肿瘤微环境，至今仍是极具挑战性的恶性肿瘤。亟需开发新策略以改善药物递送及治疗反应，而验证潜在疗法需要相关的临床前肿瘤模型。本研究比较了原位与皮下PDAC肿瘤模型在药物递送研究中的适用性。创新之处在于对肿瘤特性进行了广泛考察，包括肿瘤生长、组织病理学、功能性血管系统、灌注情况、免疫细胞浸润、生物力学特征，尤其对两种模型中胶原纤维的结构与取向进行了深入分析。研究揭示了这些因素如何影响荧光模型药物——大分子800CW的摄取，并提出了新见解。虽然原位模型提供了更具临床相关性的微环境，但皮下模型在药物递送研究中展现出独特优势，主要因其可重复性高，且胶原组织结构和灌注良好的血管系统促进了更高效的药物摄取。肿瘤对药物的摄取似乎主要受胶原纤维的结构排列、定向及灌注情况的影响。认识这些模型的多样性特征及其对药物递送的多方面影响，对于设计具有临床相关性的实验及深化对胰腺癌生物学的理解至关重要。
肿瘤(癌症)患者之家