Biomaterials are being utilized as biocompatible scaffolds or encapsulants to protect delivery of materials during their target of action. Chiefly biomaterials are ceramic, metallic, or polymeric in nature. Various types of biomaterials have been designed as drug carriers. Among them protein-based biomaterials have several specific characteristics. These include protein-specific biocompatibility, less toxicity, tunability and structural flexibility, etc. These characteristics are advantageous for biomedical applications such as drug delivery systems. Owing to these benefits, much research is devoted on the protein-based biomaterials, for the design and development of various drugs for the targeted actions.
In this dissertation, protein-based biomaterials were synthesized and utilized as potential materials for the targeted drug delivery system. This thesis mainly consists of four sections. In the first and second sections, peptide-conjugates with strong antioxidant activity were synthesized using two types of peptides along with phytochemicals. In Section I, a peptide-conjugate (Caffeic acid-APPPKK) with excellent antioxidant activity was prepared by combining silkworm-derived peptide (APPPKK) with the phytochemical caffeic acid. APPPKKK, which has high biocompatibility but weak ROS scavenging activity, and caffeic acid, which has excellent antioxidant but cytotoxicity, were combined. Conjugated Caffeic acid-APPPKK did not show toxicity even at high concentrations and made cells resistant to UVB irradiation due to their excellent ROS scavenging ability. In Section II, PGC-1α-derived peptide (TPPTTP) was combined with gallic acid. KTPPTTP was synthesized by combining lysine with TPPTTP to obtain more excellent antioxidant effect by combining two excellent gallic acids. Finally, (galloyl)₂-KTPPTTP (Gal₂-Pep) was synthesized. The synthesized Gal₂-Pep has shown excellent antioxidant activity, and the stability of the antioxidant activity was superior to that of gallic acid at room temperature under light. Particularly, mitochondrial membrane potential (MmP) tends to decrease as aging progresses, and it was confirmed that Gal₂-Pep activates MmP. From the analysis it was confirmed that the activity of elastase, a proteolytic enzyme that causes skin aging, was reduced. In the third and fourth sections, we developed a drug delivery system by synthesizing albumin-based nanoparticles. These nanoparticles released the drugs into the tumor microenvironment. In Section III, we observed that with the application of folic acid (FA)-conjugated BSA nanoparticles loaded with chlorin e6 and doxorubicin (FCDBNPs) in which the drug is released as the pH is lowered. It was confirmed that FCDBNPs were selectively uptaken by the folate receptors overexpressed in HeLa cells. In addition, it was confirmed that photodynamic therapy (PDT) and chemotherapy were possible at the same time, for effectively killing the cancer cells. In Section IV, we developed nanoparticles (RP/CA/PHNPs) in which two drugs are simultaneously released as the linker to which the drug is bound is broken in a hypoxia environment. Since the drug is released in hypoxia, which is one of the tumor microenvironments, side effects were reduced, and the effect of PDT could be increased compared to the state in which the drug was bound to nanoparticles. Because the drug was released in a hypoxic environment, the drug could penetrate deeper into the spheroid.
The application of anti-aging and drug delivery systems using protein-based biomaterials (peptide-conjugates and protein-based nanoparticles) are studied and presented in this thesis. Furthermore, it suggests that protein-based biomaterials are excellent candidates for biomedical applications.