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Exploring in vivo combinatorial chemo-immunotherapy: Addressing p97 suppression and immune reinvigoration in pancreatic can ...
1 Introduction
2 Materials and methods
2.1 Materials
2.2 Synthesis of pH-sensitive PGA-PEG and lipid-peptide conjugates
2.3 Preparation of CB+miR+R/SLN-CSW and pH-sensitive CB+miR+R/PGA-SLN-CSW
2.4 Physicochemical characterization of CB+miR+R/PGA-SLN-CSW for 28 days
2.5 Cell lines
2.6 Colocalization analysis of CB+miR+R/PGA-SLN-CSW with EGFR and PD-L1 using CLSM
2.7 Panc-02 tumor-bearing mouse model
2.8 Antitumor efficacy
2.9 Positron emission tomography/magnetic resonance imaging (PET/MRI)
2.10 Analysis of biochemical indexes and blood cell counts
2.11 Western blot analysis of the in vivo sample proteins
2.12 Immunohistochemical (IHC) analysis, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) evaluation, a ...
2.13 Biodistribution study
2.14 Evaluation of immune cell infiltration in vivo
2.15 Cytokine/chemokine immunoassay in vivo
2.16 Re-challenge study
2.17 Statistical analysis
3 Results and Discussion
3.1 Physicochemical characterization of CB+miR+R/PGA-SLN-CSW for 28 days
3.2 Targeting and intracellular distribution of CB+miR+R/PGA-SLN-CSW in Panc-02 tumor cells
3.3 The CB+miR+R/PGA-SLN-CSW formulation stimulated significant antitumor immune responses and reversed the immunosuppressi ...
3.4 The TME-responsive CB+miR+R/PGA-SLN-CSW formulation inhibited tumor growth in Panc-02-bearing mice, as validated by PET ...
3.5 Adaptable nanoformulation enhanced long-term immune memory and repolarized TAMs, boosting antitumor immune response in ...
3.6 The biosafety concerns of CB-, miR-, and/or R were improved in Panc-02 tumor-bearing mice using the PGA-SLN-CSW nanofor ...
4 Conclusions
Ethics approval and consent to participate
CRediT authorship contribution statement
Declaration of Competing Interest
Acknowledgments
Appendix A Supporting information
References
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