JS‑K Combined with a Melanin-Based Theranostic
Agent: A Novel Sequential Delivery Strategy to Enhance the Near-Infrared
Fluorescence Imaging of Pancreatic Ductal Adenocarcinoma
posted on 2024-03-01, 18:33authored byManxiong Dai, Shuo Qi, Xingyang Zhao, Lei Zhou, Quanneng Luo, Xiong Teng, Wei Cheng, Ning Zhou, Hongwen Liu, Kang Chen
Pancreatic
ductal adenocarcinoma (PDAC) is an aggressive malignancy
with a 5 year survival rate less than 12%. This malignancy is closely
related to the unique tumor microenvironment (TME), which is characterized
by a hypovascular and hyperdense extracellular matrix, making it difficult
for drugs to permeate the tumor center. Near-infrared fluorescence
(NIRF) imaging, which has high sensitivity and resolution, may improve
the survival rate of PDAC patients. In this study, we first used JS-K
(O2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl) piperazine-1-yl]
diazene-1-ium-1,2-diolate) to specifically dilate blood vessels within
the TME of PDAC patients and subsequently injected IR820-PEG-MNPs
(IPM NPs) to diagnose and treat orthotopic PDAC. We found that JS-K
promoted the accumulation of IPM NPs in orthotopic Pan02 tumor-bearing
mice and was able to increase the tumor signal-to-background ratio
(SBR) in the orthotopic PDAC area by 41.5%. In addition, surgical
navigation in orthotopic Pan02 tumor-bearing mice and complete tumor
resection based on fluorescence imaging were achieved with a detection
sensitivity of 81.0%. Moreover, we verified the feasibility of the
combination of laparoscopy and photothermal ablation (PTA) for the
treatment of PDAC. Finally, we demonstrated that IPM NPs had greater
affinity for human PDAC tissues than for normal pancreatic tissues ex vivo, preliminarily highlighting the potential for clinical
translation of these NPs. In conclusion, we developed and validated
a novel sequential delivery strategy that promotes the accumulation
of nanoagents in the tumor area and can be used for the diagnosis
and treatment of PDAC.