| Autor: |
Aiping Huang, Qingnian Li, Xinyi Shi, Junyi Gao, Yiran Ma, Jinsong Ding, Surong Hua, Wenhu Zhou |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Materials Today Bio, Vol 27, Iss , Pp 101132- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2590-0064 |
| DOI: |
10.1016/j.mtbio.2024.101132 |
| Popis: |
Pancreatic cancer is an aggressive and challenging malignancy with limited treatment options, largely attributed to the dense tumor stroma and intrinsic drug resistance. Here, we introduce a novel iron-containing nanoparticle formulation termed PTFE, loaded with the ferroptosis inducer Erastin, to overcome these obstacles and enhance pancreatic cancer therapy. The PTFE nanoparticles were prepared through a one-step assembly process, consisting of an Erastin-loaded PLGA core stabilized by a MOF shell formed by coordination between Fe3+ and tannic acid. PTFE demonstrated a unique capability to repolarize tumor-associated macrophages (TAMs) into the M1 phenotype, leading to the regulation of dense tumor stroma by modulating the activation of tumor-associated fibroblasts (TAFs) and reducing collagen deposition. This resulted in enhanced nanoparticle accumulation and deep penetration, as confirmed by in vitro multicellular tumor spheroids and in vivo mesenchymal-rich subcutaneous pancreatic tumor models. Moreover, PTFE effectively combated tumor resistance by synergistically employing the Fe3+-induced Fenton reaction and Erastin-induced ferroptosis, thereby disrupting the redox balance. As a result, significant tumor growth inhibition was achieved in mice-bearing tumor model. Comprehensive safety evaluations demonstrated PTFE's favorable biocompatibility, highlighting its potential as a promising therapeutic platform to effectively address the formidable challenges in pancreatic cancer treatment. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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