Pancreatic cancer is one of the common malignant tumors of the digestive system, and its clinical treatment is still very challenging. Most of the pancreatic cancer chemotherapeutic drugs have poor plasma stability, low cell uptake efficiency, and are prone to developing drug resistance and toxic side effects. Besides, pancreatic cancer often has a dense extracellular matrix, which consists of collagens, hyaluronic acid, and other proteoglycans. Among them, hyaluronic acid is a key component of the dense matrix, which results in vascular compression and insufficient perfusion, and hinders the delivery of chemotherapeutic drugs. In this study, we explore using hyaluronidase in tumor-bearing mice to eliminate the hyaluronic acid barrier, to reduce blood vessel compression and reshape the tumor microenvironment. In addition, we evaluate using doxorubicin-loaded nanoprobes to improve the stability and local tumor-killing effect of the drug. The nanoprobes have the characteristics of near-infrared optical imaging, which are used to monitor the tumor size in real-time during the treatment process, and dynamically observe the tumor inhibitory effect. The results show that elimination of the hyaluronic acid barrier combined with the doxorubicin-loaded nanoprobes can greatly increase drug penetration into tumor tissue and improve the effectiveness of chemotherapy drugs. This study provides a novel strategy for the treatment of pancreatic cancer.

胰腺癌是消化系统常见的恶性肿瘤之一，其临床治疗仍极具挑战性。大部分胰腺癌化疗药物血浆稳定性差，细胞摄取效率低，容易产生耐药性和毒副作用。此外，胰腺癌通常具有致密的细胞外基质，由胶原蛋白、透明质酸和其他蛋白多糖组成。其中，透明质酸是致密基质的关键成分，会导致血管受压、灌注不足，阻碍化疗药物的输送。在这项研究中，我们探索在荷瘤小鼠中使用透明质酸酶消除透明质酸屏障，减少血管压迫，重塑肿瘤微环境。此外，我们评估使用负载多柔比星的纳米探针来提高药物的稳定性和局部肿瘤杀伤效果。纳米探针具有近红外光学成像的特点，用于在治疗过程中实时监测肿瘤大小，动态观察肿瘤抑制效果。结果表明，消除透明质酸屏障结合负载阿霉素的纳米探针可以大大增加药物对肿瘤组织的渗透，提高化疗药物的有效性。该研究为胰腺癌的治疗提供了一种新的策略。用于在治疗过程中实时监测肿瘤大小，动态观察肿瘤抑制效果。结果表明，消除透明质酸屏障结合负载阿霉素的纳米探针可以大大增加药物对肿瘤组织的渗透，提高化疗药物的有效性。该研究为胰腺癌的治疗提供了一种新的策略。用于在治疗过程中实时监测肿瘤大小，动态观察肿瘤抑制效果。结果表明，消除透明质酸屏障结合负载阿霉素的纳米探针可以大大增加药物对肿瘤组织的渗透，提高化疗药物的有效性。该研究为胰腺癌的治疗提供了一种新的策略。