Drug-loaded MITOHA nanodrugs for evaluating the efficacy of targeted therapy for pancreatic cancer
Abstract The purpose of this study was to evaluate the efficiency of mitoxantrone hydrochloride (MITOHA) as a targeted pancreatic cancer therapy. MITO@HA binds to sodium hyaluronate, which is highly expressed in pancreatic cancers. This study seeks to evaluate MITO@HA treatment efficacy, clarify its inhibitory effect on pancreatic cancer, and provide an experimental basis for the use of organic polymer nanoparticles loaded with antitumor drugs to treat pancreatic cancer. This treatment strategy was developed for pancreatic cancer based on the hydrophobic behavior of the nanopharmaceutical MITO@HA. The average particle size of MITO@HA was 51.4 ± 2.3 nm, and the particles had a spherical structure. CCK-8 assays revealed that both MITO and MITO@HA inhibited the proliferation of pancreatic cancer cells. that the most suitable experimental conditions were determined to be exposing pancreatic cancer cells to 0.5 uM/L MITO@HA for 2 days. PANC-1 pancreatic cancer cells and pancreatic cancer tissues were found to express high levels of CD44. In in vitro experiments, MITO@HA inhibited G0/G1 phase arrest, increased apoptosis, and decreased cell replication, cell migration and invasion in the pancreatic cancer cell cycle compared to MITO alone. Therefore, we believe that MITO@HA has a good tumor cell inhibitory effect. Furthermore, in vivo experiments revealed that the tumor volume in nude mice in the MITO@HA group decreased (P < 0.05), and both MITO and MITO@HA treatment decreased the tumor growth curves, with MITO@HA decreasing them more than MITO alone. Compared with those in the control group and the MITO group, the HE staining of tumors in the MITO@HA group showed massive liquefaction necrosis of the tumor tissues. Safety evaluation of the nude mice in the MITO@HA group revealed that the mice had a normal blood profile, normal liver and kidney function, and normal myocardial enzymes. The above results indicate that MITO@HA can effectively accumulate in pancreatic cancer tumor tissue through the EPR effect and CD44 receptor targeting, leading to liquefaction and necrosis of tumor tissue, thereby effectively reducing tumor growth. The above results showed that MITO@HA is highly safe and can enhance the antitumor effect on pancreatic cancer, providing an experimental basis for clinical application..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
ResearchSquare.com - (2024) vom: 26. Feb. Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Fengjun [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.21203/rs.3.rs-3972887/v1 |
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| PPN (Katalog-ID): |
XRA042625246 |
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| 520 | |a Abstract The purpose of this study was to evaluate the efficiency of mitoxantrone hydrochloride (MITOHA) as a targeted pancreatic cancer therapy. MITO@HA binds to sodium hyaluronate, which is highly expressed in pancreatic cancers. This study seeks to evaluate MITO@HA treatment efficacy, clarify its inhibitory effect on pancreatic cancer, and provide an experimental basis for the use of organic polymer nanoparticles loaded with antitumor drugs to treat pancreatic cancer. This treatment strategy was developed for pancreatic cancer based on the hydrophobic behavior of the nanopharmaceutical MITO@HA. The average particle size of MITO@HA was 51.4 ± 2.3 nm, and the particles had a spherical structure. CCK-8 assays revealed that both MITO and MITO@HA inhibited the proliferation of pancreatic cancer cells. that the most suitable experimental conditions were determined to be exposing pancreatic cancer cells to 0.5 uM/L MITO@HA for 2 days. PANC-1 pancreatic cancer cells and pancreatic cancer tissues were found to express high levels of CD44. In in vitro experiments, MITO@HA inhibited G0/G1 phase arrest, increased apoptosis, and decreased cell replication, cell migration and invasion in the pancreatic cancer cell cycle compared to MITO alone. Therefore, we believe that MITO@HA has a good tumor cell inhibitory effect. Furthermore, in vivo experiments revealed that the tumor volume in nude mice in the MITO@HA group decreased (P < 0.05), and both MITO and MITO@HA treatment decreased the tumor growth curves, with MITO@HA decreasing them more than MITO alone. Compared with those in the control group and the MITO group, the HE staining of tumors in the MITO@HA group showed massive liquefaction necrosis of the tumor tissues. Safety evaluation of the nude mice in the MITO@HA group revealed that the mice had a normal blood profile, normal liver and kidney function, and normal myocardial enzymes. The above results indicate that MITO@HA can effectively accumulate in pancreatic cancer tumor tissue through the EPR effect and CD44 receptor targeting, leading to liquefaction and necrosis of tumor tissue, thereby effectively reducing tumor growth. The above results showed that MITO@HA is highly safe and can enhance the antitumor effect on pancreatic cancer, providing an experimental basis for clinical application. | ||
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| 700 | 1 | |a Xu, Zhiyang |4 aut | |
| 700 | 1 | |a Jia, Xiaochao |4 aut | |
| 700 | 1 | |a Tang, Yidan |4 aut | |
| 700 | 1 | |a Chen, Mingsheng |4 aut | |
| 700 | 1 | |a Chen, Chuan |4 aut | |
| 700 | 1 | |a Fang, Fang |4 aut | |
| 700 | 1 | |a Shi, Xiudong |4 aut | |
| 700 | 1 | |a Chen, Tianyou |4 aut | |
| 700 | 1 | |a Shi, Yuxin |4 aut | |
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