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@PHDTHESIS{Chen:1017036,
      author       = {Chen, Junlin},
      othercontributors = {Kiessling, Fabian and Herrmann, Andreas},
      title        = {{P}olymeric microbubbles for m{RNA} delivery and molecular
                      imaging},
      school       = {Rheinisch-Westfälische Technische Hochschule Aachen},
      type         = {Dissertation},
      address      = {Aachen},
      publisher    = {RWTH Aachen University},
      reportid     = {RWTH-2025-07096},
      pages        = {1 Online-Ressource : Illustrationen},
      year         = {2025},
      note         = {Veröffentlicht auf dem Publikationsserver der RWTH Aachen
                      University; Dissertation, Rheinisch-Westfälische Technische
                      Hochschule Aachen, 2025, Kumulative Dissertation},
      abstract     = {Microbubbles (MB) are hollow, air-filled particles that
                      have garnered increasing attention in gene delivery and
                      ultrasound (US) molecular imaging. In mRNA delivery, MB are
                      used as enhancers to improve DNA and mRNA passage through
                      biological barriers under US exposure. However, it has
                      remained unclear whether nanocarrier-encapsulated mRNA
                      should be administered separately (co-administration) or
                      conjugated to MB (co-formulation). Therefore, we analyzed
                      the impact of poly(n-butyl cyanoacrylate) MB (PBCA-MB)
                      co-administration with mRNA-DOTAP/DOPE lipoplexes or their
                      co-formulation on the transfection of cancer cells in vitro
                      and in vivo. Our studies demonstrate that PBCA-MB combined
                      with US are highly suited to enhance mRNA transfection
                      efficacy in vitro and in vivo. Under focused US exposure,
                      co-formulation mainly transfected (peri)vascular tissue.
                      Compared to co-formulation, co-administration reached deeper
                      tumor tissues, thus resulting in higher transfection
                      efficiency. On the other hand, compared to
                      co-administration, co-formulation induced less off-site
                      transfection, and the transfection by the co-formulation
                      approach was more dependent on the ultrasound trigger.
                      Consequently, the choice between co-administration and
                      co-formulation should be thoroughly considered based on the
                      specific targets and objectives when delivering nucleic
                      acids. Additionally, the development of MB-based
                      co-formulation approaches relies heavily on bioconjugate
                      chemistries. However, introducing functional ligands to MB
                      surfaces has been challenging, as conventional methods for
                      functionalizing PBCA-MB often require multi-step synthesis,
                      leading to low MB yield, poor controllability, and limited
                      reproducibility. In this context, we developed a novel
                      single-step aminolysis protocol to generate functionalized
                      PBCA-MB as ultrasound contrast agents. To comprehensively
                      characterize this method's efficacy in introducing
                      functional ligands to MB, actively-targeting MB were
                      generated and we display that they were capable of binding
                      efficiently to inflammatory endothelium under in vitro, ex
                      vivo, and in vivo conditions for breast cancer detection.
                      Our results demonstrated that the aminolysis protocol
                      significantly outperformed conventional functionalization
                      strategies (hydrolysis and carbodiimide chemistry) in terms
                      of simplicity, higher MB yield, and improved controllability
                      and reproducibility. This innovative method has the
                      potential to facilitate the transition from laboratory-scale
                      production to large-scale manufacturing, thereby reducing
                      costs and accelerating clinical translation of MB-based
                      technologies in both gene delivery and molecular imaging
                      applications.},
      cin          = {811003-3 ; 924210},
      ddc          = {610},
      cid          = {$I:(DE-82)811003-3_20140620$},
      pnm          = {GRK 2375 - GRK 2375: Tumor-Targeted Drug Delivery
                      (331065168) / DFG project G:(GEPRIS)445703531 - KFO 5011:
                      Integration neuer Methoden zur Verbesserung von
                      translationaler Nierenforschung (445703531) / DFG project
                      G:(GEPRIS)233312120 - Weiterentwicklung der
                      bewegungsmodellbasierten
                      Ultraschall-Lokalisationsmikroskopie zur Unterstützung der
                      Brustkrebsdiagnostik und Therapieüberwachung in Patienten
                      (233312120)},
      pid          = {G:(GEPRIS)331065168 / G:(GEPRIS)445703531 /
                      G:(GEPRIS)233312120},
      typ          = {PUB:(DE-HGF)11},
      doi          = {10.18154/RWTH-2025-07096},
      url          = {https://publications.rwth-aachen.de/record/1017036},
}