背景：胰腺癌主要由胰腺导管腺癌（PDAC）组成，是一种高度恶性的疾病，通常被称为缺氧肿瘤微环境。临床上应用PDT治疗胰腺癌仍存在一些问题，包括：（i）胰腺癌深部位置；（ii）光纤引起的组织损伤；（iii）缺氧微环境；（iv）传统光敏剂的短激发波长；以及（v）光敏剂的传递效率低等。方法：我们设计了一种有机纳米颗粒作为近红外II（NIR-II）荧光成像的光敏剂，通过近红外（808 nm）激光激发对深部原位胰腺肿瘤产生一类I PDT效应。结果：这种新型光敏剂在小鼠原位胰腺癌中具有增强的积累能力，并可用于有效检测胰腺癌并引导后续激光照射以进行准确的深部胰腺癌PDT。此外，我们构建了一个通过NIR-II荧光成像监测的内窥镜平台，实现了微创内窥镜引导的干预性光动力疗法（EG-iPDT），有效抑制了原位胰腺癌，在小鼠模型中使总生存期延长至78天，与PBS + EG-iPDT组相比（*p < 0.05）。结论：微创EG-iPDT对于早期、不能切除或转移的胰腺癌具有潜在治疗前景。©作者。

Rationale: Pancreatic cancer, comprising mostly pancreatic ductal adenocarcinoma (PDAC), is a highly malignant disease, typically known as a hypoxic tumor microenvironment. The application of PDT in pancreatic cancer in clinic is still hampered by several shortcomings, including the (i) deep location of pancreatic cancer, (ii) tissue damage induced by optical fibers, (iii) hypoxic microenvironment, (iv) short excitation wavelengths of traditional photosensitizers, and (v) poor delivery efficiency of photosensitizers. Methods: We designed an organic nanoparticle as photosensitizer for near-infrared II (NIR-II) fluorescent (FL) imaging that exerts a type I PDT effect on deep orthotopic pancreatic tumors under excitation by a NIR (808 nm) laser. Results: This novel photosensitizer exhibits enhanced accumulation in orthotopic pancreatic cancer in mice and could be used to effectively detect pancreatic cancer and guide subsequent laser irradiation for accurate PDT of deep pancreatic cancer. In addition, we built an endoscopic platform monitored by NIR-II FL imaging to achieve minimally invasive endoscopically guided interventional photodynamic therapy (EG-iPDT) with efficient inhibition of orthotopic pancreatic cancer, which prolonged overall survival up to 78 days compared to PBS + EG-iPDT group (*p < 0.05) in a mouse model. Conclusions: Minimally invasive EG-iPDT has promise as an intraoperative treatment for early-stage or unresectable or metastatic pancreatic cancer.© The author(s).