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基于近红外二区荧光纳米颗粒的内镜引导下介入光动力疗法治疗原位胰腺导管腺癌。

Endoscopically guided interventional photodynamic therapy for orthotopic pancreatic ductal adenocarcinoma based on NIR-II fluorescent nanoparticles.

机构信息

Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha 410005, P. R. China.

Translational Medicine Laboratory of Pancreas Disease of Hunan Normal University, Changsha 410005, P. R. China.

出版信息

Theranostics. 2023 Aug 6;13(13):4469-4481. doi: 10.7150/thno.84164. eCollection 2023.

DOI:10.7150/thno.84164
PMID:37649601
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10465211/
Abstract

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. 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. 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 (* < 0.05) in a mouse model. Minimally invasive EG-iPDT has promise as an intraoperative treatment for early-stage or unresectable or metastatic pancreatic cancer.

摘要

胰腺癌主要包括胰腺导管腺癌 (PDAC)，是一种高度恶性的疾病，通常被认为是一种缺氧的肿瘤微环境。PDT 在胰腺癌中的临床应用仍然受到几个缺点的限制，包括 (i) 胰腺癌的位置深，(ii) 光纤引起的组织损伤，(iii) 缺氧的微环境，(iv) 传统光敏剂的短激发波长，以及 (v) 光敏剂的递送效率差。我们设计了一种有机纳米颗粒作为光敏剂，用于近红外 II (NIR-II) 荧光 (FL) 成像，在 NIR (808nm) 激光激发下，对原位胰腺肿瘤发挥 I 型 PDT 作用。这种新型光敏剂在原位胰腺癌小鼠中表现出增强的积累，可用于有效检测胰腺癌，并指导随后的激光照射，以实现对深部胰腺癌的准确 PDT。此外，我们构建了一个由 NIR-II FL 成像监测的内镜平台，以实现微创内镜引导下的光动力治疗 (EG-iPDT)，有效地抑制原位胰腺癌，与 PBS+EG-iPDT 组相比，在小鼠模型中总生存期延长至 78 天 (*<0.05)。微创 EG-iPDT 有望成为早期或不可切除或转移性胰腺癌的术中治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a38/10465211/61907705f634/thnov13p4469g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a38/10465211/61907705f634/thnov13p4469g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a38/10465211/bef64d8d0449/thnov13p4469g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a38/10465211/647cfc4bfdb3/thnov13p4469g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a38/10465211/53535dffc30b/thnov13p4469g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a38/10465211/d45bf3863278/thnov13p4469g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a38/10465211/61907705f634/thnov13p4469g007.jpg

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