TY - JOUR
T1 - Efficient pre-Treatment for pancreatic cancer using chloroquine-loaded nanoparticles targeting pancreatic stellate cells
AU - Matsumoto, Sokichi
AU - Nakata, Kohei
AU - Sagara, Akiko
AU - Guan, Weiyu
AU - Ikenaga, Naoki
AU - Ohuchida, Kenoki
AU - Nakamura, Masafumi
N1 - Funding Information:
The present study was partially supported by The Japan Society for the Promotion of Science Grants‑in‑Aid and for Young Scientists Grant (grant nos. JP18H02880, JP19H03732, JP19K18153 and JP20H03754), The Takeda Science Foundation, The Kobayashi Foundation for Cancer Research and The Shinnihon Foundation of Advanced Medical Treatment Research.
Publisher Copyright:
© 2021 Spandidos Publications. All rights reserved.
PY - 2021/7
Y1 - 2021/7
N2 - 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.
AB - 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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U2 - 10.3892/ol.2021.12894
DO - 10.3892/ol.2021.12894
M3 - Article
AN - SCOPUS:85109107582
SN - 1792-1074
VL - 22
JO - Oncology Letters
JF - Oncology Letters
IS - 2
M1 - 633
ER -
