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Ionizable cationic lipid nanoparticles loaded with miRNA‐125b/BLZ945 for pancreatic cancer treatment.

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Title: Ionizable cationic lipid nanoparticles loaded with miRNA‐125b/BLZ945 for pancreatic cancer treatment.
Authors: Zhang, Jiajie1,2 (AUTHOR), Qu, Ming3,4 (AUTHOR), Mo, Zhanhao3,4 (AUTHOR), Sui, He3,4 (AUTHOR), Liu, Lin3,4 (AUTHOR), Fu, Deliang1 (AUTHOR) 16111220055@fudan.edu.cn
Source: Biotechnology & Applied Biochemistry. Jun2025, Vol. 72 Issue 3, p846-857. 12p.
Subjects: Cationic lipids, Pancreatic tumors, Pancreatic cancer, Nucleic acids, Macrophages
Abstract: In prior research, both miRNA‐125b and BLZ945 have shown potential in effectively inhibiting M2 macrophage polarization and producing antitumor effects. Nevertheless, their physicochemical characteristics present significant challenges for efficient in vivo delivery. Ionizable cationic lipid nanoparticles (LNPs), recognized for their superior biocompatibility and drug‐loading capacity, serve as a novel carrier for nucleic acid‐based therapeutics. In our study, we successfully encapsulated both agents within LNPs and conducted a thorough characterization. Subsequently, we investigated their potential to repolarize M2 macrophages in vitro and evaluated their in vivo distribution, biosafety, and antitumor efficacy. The findings revealed that the LNPs maintained excellent drug‐loading efficiency, consistent particle size, and stable zeta potential. All formulations effectively inhibited M2 macrophage polarization in vitro. Upon administration in vivo, the LNPs not only demonstrated favorable biosafety profiles but also accumulated efficiently in tumor tissues, substantially reducing tumor burden, particularly notable in co‐loaded LNPs. Our results affirm that LNPs are an effective carrier for miRNA‐125b and BLZ945, highlighting this encapsulation approach as promising for the treatment of solid tumors and meriting further investigation. Practitioner points: (i) Ionizable cationic nanoparticles provide high and stable encapsulation rates to efficiently load nucleic acid polymers into the LNP, avoiding the rapid accumulation of circulating macrophages, which can lead to reduced penetration of the LNP into target tissues. Therefore, it can be used as a novel drug delivery method to benefit clinical patients. (ii) miRNA‐125b LNP/BLZ945 LNP attenuated the depleting effect of BLZ945 on macrophages and significantly inhibited macrophage M2 polarization. It could be effectively distributed in tumors and showed good biosafety while exerting antitumor effects, bringing hope to clinical pancreatic tumor patients. [ABSTRACT FROM AUTHOR]
Copyright of Biotechnology & Applied Biochemistry is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Label: Title
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  Data: Ionizable cationic lipid nanoparticles loaded with miRNA‐125b/BLZ945 for pancreatic cancer treatment.
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  Data: <searchLink fieldCode="AR" term="%22Zhang%2C+Jiajie%22">Zhang, Jiajie</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Qu%2C+Ming%22">Qu, Ming</searchLink><relatesTo>3,4</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Mo%2C+Zhanhao%22">Mo, Zhanhao</searchLink><relatesTo>3,4</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Sui%2C+He%22">Sui, He</searchLink><relatesTo>3,4</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Liu%2C+Lin%22">Liu, Lin</searchLink><relatesTo>3,4</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Fu%2C+Deliang%22">Fu, Deliang</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> 16111220055@fudan.edu.cn</i>
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  Data: <searchLink fieldCode="JN" term="%22Biotechnology+%26+Applied+Biochemistry%22">Biotechnology & Applied Biochemistry</searchLink>. Jun2025, Vol. 72 Issue 3, p846-857. 12p.
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  Data: <searchLink fieldCode="DE" term="%22Cationic+lipids%22">Cationic lipids</searchLink><br /><searchLink fieldCode="DE" term="%22Pancreatic+tumors%22">Pancreatic tumors</searchLink><br /><searchLink fieldCode="DE" term="%22Pancreatic+cancer%22">Pancreatic cancer</searchLink><br /><searchLink fieldCode="DE" term="%22Nucleic+acids%22">Nucleic acids</searchLink><br /><searchLink fieldCode="DE" term="%22Macrophages%22">Macrophages</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: In prior research, both miRNA‐125b and BLZ945 have shown potential in effectively inhibiting M2 macrophage polarization and producing antitumor effects. Nevertheless, their physicochemical characteristics present significant challenges for efficient in vivo delivery. Ionizable cationic lipid nanoparticles (LNPs), recognized for their superior biocompatibility and drug‐loading capacity, serve as a novel carrier for nucleic acid‐based therapeutics. In our study, we successfully encapsulated both agents within LNPs and conducted a thorough characterization. Subsequently, we investigated their potential to repolarize M2 macrophages in vitro and evaluated their in vivo distribution, biosafety, and antitumor efficacy. The findings revealed that the LNPs maintained excellent drug‐loading efficiency, consistent particle size, and stable zeta potential. All formulations effectively inhibited M2 macrophage polarization in vitro. Upon administration in vivo, the LNPs not only demonstrated favorable biosafety profiles but also accumulated efficiently in tumor tissues, substantially reducing tumor burden, particularly notable in co‐loaded LNPs. Our results affirm that LNPs are an effective carrier for miRNA‐125b and BLZ945, highlighting this encapsulation approach as promising for the treatment of solid tumors and meriting further investigation. Practitioner points: (i) Ionizable cationic nanoparticles provide high and stable encapsulation rates to efficiently load nucleic acid polymers into the LNP, avoiding the rapid accumulation of circulating macrophages, which can lead to reduced penetration of the LNP into target tissues. Therefore, it can be used as a novel drug delivery method to benefit clinical patients. (ii) miRNA‐125b LNP/BLZ945 LNP attenuated the depleting effect of BLZ945 on macrophages and significantly inhibited macrophage M2 polarization. It could be effectively distributed in tumors and showed good biosafety while exerting antitumor effects, bringing hope to clinical pancreatic tumor patients. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Biotechnology & Applied Biochemistry is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1002/bab.2701
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        Text: English
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        PageCount: 12
        StartPage: 846
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      – SubjectFull: Cationic lipids
        Type: general
      – SubjectFull: Pancreatic tumors
        Type: general
      – SubjectFull: Pancreatic cancer
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      – SubjectFull: Nucleic acids
        Type: general
      – SubjectFull: Macrophages
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      – TitleFull: Ionizable cationic lipid nanoparticles loaded with miRNA‐125b/BLZ945 for pancreatic cancer treatment.
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            NameFull: Zhang, Jiajie
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            NameFull: Qu, Ming
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              M: 06
              Text: Jun2025
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              Y: 2025
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