Strategies for targeted and image guided drug delivery for solid tumor therapy

Ayele Hailu Negussie*

*Corresponding author for this work

Research output: ThesisPhD Thesis - Research external, graduation UT

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Abstract

The three main cancer treatment modalities are surgery, radiotherapy, and chemotherapy Unfortunately, they are too often associated with high risks of injury, or toxicity to healthy tissues. Therefore, more selective treatment paradigms and adjuvant combination methods that can kill tumor cells with the promise of limited or no side-effects are being investigated including immunotherapy, drug delivery systems (DDS), and drug delivery devices (DDDs). Ideally, combining two or more of these strategies will realize even more selective treatments with better safety and efficacy.
In this thesis work two ‘different scale’ strategies for the treatment of cancer have been explored:1) NANO-scale: thermosensitive liposomes that target tumor vasculature and imageable thermosensitive liposomes for MR-HIFU therapy and 2) MICRO-scale: imageable microparticles as a drug delivery device. Investigation of such strategies has not only therapeutic clinical implications but also can shed light on therapeutic mechanisms and improve our understanding required for the optimization of future drug delivery approaches.
The image-able thermosensitive liposome in combination with heat sources such as high intensity focused ultrasound (HIFU), radiofrequency (RF), microwave (MW), or laser ablation used for enhanced drug deposition and monitoring of the fate of delivered drug within the tumor.
The cNGR-LTSLs demonstrate improved avidity of a cNGR-targeted LTSL for CD13-positive HT- 1080 cells, as a result of multiple cNGR coupling to the liposome surface. The improved avidity of cNGR-targeted LTSL to vascular receptors achieved by surface attachment of the ligand may translate into increased drug delivery to tumor cells in vivo, as the target vascular receptors are well accessible from the bloodstream.
The micro-sized particles reported are radiopaque drug-eluting microparticles containing iodine or bismuth radiopacifiers which were successfully synthesized by direct chemical conjugation of a radio-dense triiodo phenyl species or bismuth chelated macrocycle to microparticles, and which are also able to carry cationic drugs like doxorubicin. These image-able embolic microparticles are visible under fluoroscopy and CBCT which enables real- time feedback of bead location (and thus localization of drug and therapeutic ischemic effect) during and after DEB-TACE.
This thesis addresses the successful formulation of image-guided, targeted and locoregional drug delivery systems based on nanometer- and micrometer-sized particles, respectively.



Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Biomaterials Science and Technology
Supervisors/Advisors
  • Storm, G. , Supervisor
  • Moonen, Chrit T.W., Supervisor, External person
Award date9 Jun 2021
Place of PublicationEnschede
Publisher
Print ISBNs978-90-365-5183-0
DOIs
Publication statusPublished - 9 Jun 2021

Keywords

  • Drug delivery
  • Imageable
  • Nano and micro particles
  • Cancer
  • TACE
  • CT
  • CBCT
  • HCC
  • Targeted cancer therapy
  • HIFU
  • NGR
  • Dual energy CT (DECT)

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