Journal
ONCOLOGY LETTERS
Volume 22, Issue 2, Pages -Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ol.2021.12894
Keywords
chloroquine; combination therapy; desmoplasia; nanoparticles; orthotopic xenograft; pancreatic cancer; pancreatic ductal adenocarcinoma; pre-treatment; stroma
Categories
Funding
- Japan Society for the Promotion of Science [JP18H02880, JP19H03732, JP19K18153, JP20H03754]
- Takeda Science Foundation
- Kobayashi Foundation for Cancer Research
- Shinnihon Foundation of Advanced Medical Treatment Research
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In this study, PLGA nanoparticles were used to deliver chloroquine to pancreatic tumors, effectively reducing PSC activation and showing promise as a novel pre-treatment strategy for PDAC.
Pancreatic stellate cells (PSCs) play a key role in desmoplastic stroma, which is a characteristic of pancreatic ductal adenocarcinoma (PDAC), and they also enhance the malignancy of pancreatic cancer cells. Our previous study reported chloroquine's mitigating effects on PSC activation; however, the drug is known to induce adverse effects in clinical practice. The present study aimed to reduce chloroquine doses and develop a useful pre-treatment that targets PSCs using nanoparticles. Poly lactic-co-glycolic acid (PLGA) nanoparticles were used as carriers and loaded with indocyanine green (Nano-ICG) or chloroquine (Nano-CQ). Tumor accumulation of Nano-ICG was evaluated using an in vivo imaging system. The effects of chloroquine, Nano-CQ and/or chemotherapy drug gemcitabine were investigated in an orthotopic xenograft mouse model. Nano-ICG selectively accumulated in pancreatic tumors and persisted therein for over 7 days after administration. Additionally, Nano-ICG accumulated in the peritoneal metastasized regions, but not in the liver, kidney and normal pancreatic tissues. Nano-CQ reduced the density of activated PSCs at lower chloroquine doses and significantly restrained tumor progression in combination with gemcitabine. In conclusion, the PLGA nanosystem successfully delivered the drug to pancreatic tumors. Nano-CQ efficiently reduced PSC activation and may be a promising novel pre-treatment strategy for PDAC.
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