Effective cancer treatment requires its early diagnosis and safe drug delivery systems. Up to date many therapeutics have failed due to their limited ability to reach the diseased site selectively without damaging healthy cells. Furthermore, none of the existing imaging techniques is absolutely reliable due to the differences in resolution and sensitivity. Therefore, synergistic combination of imaging modalities in one probe is the key strategy to benefit, for example, from the sensitive and quantifiable PET signal and the high resolution of MRI. Nanozeolites are among the most promising candidates for realization of this concept due to their unique crystalline structure capable of stable loading with metal-ions with diagnostic and therapeutic properties. Even though, these materials have found many applications in various technologies, their medicinal use has not been fully explored yet.
This research is aiming at exploitation of smart hierarchical nanozeolites with modified framework. The mesoporous fragments in the framework will be used for encapsulation of drug molecules (e.g. doxorubicin), while small cavities will be irreversibly loaded with paramagnetic metal-ions (MRI) and PET-tracers. The in vivo efficacy of the designed materials will rely on over-expression of specific molecules (sialic acid) and enzymes (proteases) in tumors compared to healthy regions. Specific surface modification with conjugated phenylboronic moieties and the bulky poly-L-glutamic acid will render nanozeolites with responsive properties: the ability to recognize over-expressed sialic acid in tumors followed by enzymatic cleavage of sugar residues by proteases and release of the drug. Moreover, enzymatic hydrolysis of the coating will open up the pores giving water molecules access to the zeolite interior and hence increase relaxivity as well as trigger the local release of the drug.