|dc.description.abstract||Specifically targeting cancer cells is much more efficient than non-targeted treatment because it decreases side effects and permits stronger treatment without as a risk of harming normal cells. Smart molecular probes and materials capable of passively or actively targeting cancerous cells show potential in cancer treatment for this reason. The combination of Metal-Organic Frameworks (MOFs) with actively targeting molecules provides an attractive way for targeted cancer theranostic methods. In this work, peptide sequences were synthesized that have high affinity and specificity towards proteins expressed on the surface of cancer cells. To introduce enough flexibility for targeted binding and provide extra functionality, the targeting peptide AP2H was further modified with polyethylene glycol (PEG) as a spacer molecule, and the peptide RGDG was used in place of RGD in order to use the additional glycine residue as a spacer molecule. After solid phase synthesis and cleavage, the resultant peptides were characterized with high-performance liquid chromatography (HPLC) and mass spectrometry (MS). Biocompatible metal-organic frameworks ZIF-8, UiO-66, and UiO-66-NH2 were synthesized. UiO-66-NH2 was functionalized with the peptide sequences to build a targetable delivery system using the MOF to carry molecules, such as fluorescent probes or anticancer drugs, directly to tumor cells by using the targeting peptides RGD and AP2H.
Doxorubicin (DOX), a typical anticancer drug, was used as a model to determine whether the peptide-guided delivery system has the potential for carrying molecular cargos. UV-Vis spectrophotometry was used to quantitatively measure the uptake and subsequent release of DOX. The DOX-encapsulated MOF paired with a targeting peptide can be promising as a targetable delivery system for cancer treatment.||en