## 2 Keratin-Based Nanoparticles
### Human Hair Keratin-Based Nanoparticles
According to the authors, the PDA/keratin coating of MSNs could reduce their toxicity by limiting the interaction with cells membranes, thus allowing the system to reach the tumor environment where, thanks to the presence of elevated GSH concentration, the PDA/keratin coating would be degraded, allowing the release of the MSN's cargo. The responsiveness of MSNs@PDA@keratin nanoparticles was evaluated at different pH and GSH concentrations, showing that nanoparticles size dramatically increased both under acidic and reductive conditions (pH = 5; GSH 10 mM), while the zeta potential switched from negative to positive, most likely due to the sulfhydryl-disulfhydryl exchange reaction. Finally, to further prove the potential of their system, the authors loaded the anticancer drug doxorubicin (DOX) onto MSNs@PDA@keratin nanoparticles (see Section 2.1.1). In 2020, [PERSON] reported a study where keratin and albumin were used to improve the biocompatibility and storage stability of gold nanoparticles (AuNPs) [27]. The authors prepared blank AuNPs, keratin-functionalized AuNPs (KP-AuNPs), albumin-functionalized AuNPs (AP-AuNPs), and keratin-albumin-functionalized AuNPs (KP-AP-AuNPs) by mixing an aqueous solution of 0.01 M HAuCl\({}_{4}\)3H\({}_{2}\)O with the proteins dissolved in water at different concentrations (Figure 3). Figure 3: Schematic preparation procedure of (**a**) KP-AuNPs, (**b**) AP-AuNPs, and (**c**) KP-AP-AuNPs. Figure 2: (**a**) DPPH and (**b**) ABTS radical scavenging activities of vitamin C, NANO, and EGCG at different concentrations. The “\(\ast\ast\)”, and “\(\ast\ast\)” represent \(p<0.05\), and \(p<0.01\). Reprinted and adapted with permission from [25]. Copyright 2021 American Chemical Society. The successful AuNPs functionalization was confirmed through various characterization techniques, and results revealed that the interaction between the proteins and the AuNPs surface through cysteine and amine groups ultimately determines a significant size increase (from 38 nm till 590 nm). The cytocompatibility, hemocompatibility, and stability, including long-term storage stability (six months), under different pH conditions were studied and assessed with surface plasmon resonance, suggesting promising properties of protein functionalized nanoparticles as opposed to plain AuNPs. Importantly, results from these authors show that unfunctionalized AuNPs induce an 8% red blood cells lysis, whereas the protein-functionalized particles reached only 2%, and no significant differences were observed in the hemolytic profile of KP-AuNPs, AP-AuNPs, and KP-AP-AuNPs. Overall, the work by [PERSON] and colleagues indicated that keratin alone or in combination with albumin could serve as an effective functional protein for augmenting gold nanoparticles biocompatibility and stability. Patients affected by type II diabetes mellitus (T2 DM) experience compromised parameters of glucose metabolism and removal along with peripheral insulin resistance, which leads to the development of complications such as chronic hyperglycemia, and acute glycemic fluctuations [28]. [PERSON] and co-workers recently focused their studies on the use of human hair keratin as carriers of indolequinoxaline (INDX) derivatives for the treatment of T2 DM [29]. This pathogenic condition leads to hyperglycemia and, therefore, more insulin is required to take up glucose into the muscle, adipocytes, and liver. Numerous studies have demonstrated that activation of adenosine monophosphate-activated protein kinase (AMPK) and down regulation of protein tyrosine phosphatase 1B (PTP1B) are beneficial for treating T2 DM. Therefore, the authors designed and synthesized INDX derivatives incorporated into keratin NPs by the solid dispersion method [30,31]. The entrapment efficiency and loading capacity of INDX into the keratin carrier were 89 and 11.9%, respectively.