Journal
NANO TODAY
Volume 44, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.nantod.2022.101458
Keywords
Pancreatic ductal adenocarcinoma; Tumor mechanics; Cancer-associated fibroblasts; Cancer stem cells; Hyperbaric oxygen; Cancer therapy
Categories
Funding
- Research Core Facilities for Life Science (HUST)
- Optical Bioimaging Core Facility of WNLO-HUST
- Analytical and Testing Center of HUST
- National Research and Development Program of China [2018YFA0208900, 2020YFA0211200, 2020YFA0710700]
- National Science Foundation of China [82172757, 31972927]
- Scientific Research Foundation of Huazhong University of Science and Technology [82172757]
- Program for HUST Academic Frontier Youth Team [82172757]
- HCP Program for HUST
- [3004170130]
- [2018QYTD01]
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Hyperbaric oxygen therapy can enhance the therapeutic efficacy of Abraxane and gemcitabine in the treatment of pancreatic ductal carcinoma by inhibiting cancer-associated fibroblasts, reducing extracellular matrix components, and improving drug delivery. It also regulates the niche of cancer stem cells. Translating this combination therapy to bedside applications is feasible.
While the combination of Abraxane and gemcitabine (GEM) has been approved as a first-line therapy for the treatment of advanced pancreatic ductal carcinoma (PDAC), the clinical antitumor efficacy is dismal thus far. Here, we explore hyperbaric oxygen (HBO) therapy to boost antitumor efficacy of Abraxane and GEM against murine PDAC Panc02 tumors. Mechanistically, we reveal that HBO significantly constrains cancer associated fibroblasts (CAFs) by disrupting hypoxia. As CAFs are the main producers of extracellular matrix (ECM) components, HBO effectively reduces collagen I and fibronectin, leading to normalization of not only tumor mechanics but also blood vessels. Therefore, HBO augments drug delivery in terms of tumor accumulation, penetration, and cellular internalization. Furthermore, we demonstrate that HBO helps Abraxane and GEM eliminate cancer stem cells (CSCs) by regulating CAFs mediated CSCs niche. Consequently, HBO potentiates antitumor efficacy of Abraxane and GEM by inhibiting not only primary tumors but more importantly metastases of Panc02 tumors, with negligible side effects. Given HBO, Abraxane, and GEM are routinely applied in clinical practice, their combination is readily translatable to bedside applications.(c) 2022 Elsevier Ltd. All rights reserved.
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