Nanoprodrugs with responsive release properties integrate the advantages of stimuli-responsive prodrugs and nanotechnology. They would provide ultimate opportunity in fighting atherosclerosis. In this study, we synthesized a redox-responsive nanoprodrug of simvastatin (TPTS) by conjugating α-tocopherol polyethylene glycol derivative to the pharmacophore of simvastatin with a thioketal linker. TPTS formed nanoparticles and released parent simvastatin in the presence of hydrogen peroxide. Moreover, by taking advantage of the self-assembly behavior of TPTS, we developed a fibronectin-targeted delivery system (TPTS/C/T) to codelivery simvastatin prodrug and ticagrelor. In vitro and in vivo experiments indicated that TPTS and TPTS/C/T had good stability, which could reduce off-target leakage of drugs. They greatly inhibited the M1-type polarization of macrophages; reduced intracellular reactive oxygen species level and inflammatory cytokine; and TNF-α, MCP-1, and IL-1β were secreted by macrophage cells, thus providing enhanced anti-inflammatory and antioxidant effects compared with free simvastatin. TPTS/C/T realized targeted drug release to plaques and synergistic therapeutic effects of simvastatin and ticagrelor on atherosclerosis treatment in an ApoE–/– mouse model, resulting in excellent atherosclerosis therapeutic efficacy and a promising biosafety profile. Therefore, this study provides a new method for manufacturing statin nanodrugs and a new design idea for related responsive drug release nanosystems for atherosclerosis.

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An Al/ZrO2/IL/n-Si (IL: interface layer) MOS capacitor has been fabricated by metal organic decomposition of ZrO2 and thermal deposition Al. We have measured parallel capacitance (Cm) and parallel resistance (Rm) versus bias voltage curves (Cm, Rm–V) at different AC signal frequency (f), and Cm, Rm–f curves at different bias voltage. The curves of Cm, Rm–f measurements show obvious frequency dispersion in the range of 100 kHz–2 MHz. The energy band profile shows that a large voltage is applied on the ZrO2 layer and IL at accumulation, which suggests possible dielectric polarization processes by some traps in ZrO2 and IL. Cm, Rm–f data are used for frequency dispersion analysis. To exclude external frequency dispersion, we have extracted the parameters of C (real MOS capacitance), Rp (parallel resistance), CIL (IL capacitance), RIL (IL resistance) and Rs (Si resistance) in a five-element model by using a three-frequency method. We have analyzed intrinsic frequency dispersion of C, Rp, CIL, RIL and Rs by studying the dielectric characteristics and Si surface layer characteristics. At accumulation, the dispersion of C and Rp is attributed to dielectric polarization such as dipolar orientation and oxide traps. The serious dispersion of CIL and RIL are relative to other dielectric polarization, such as border traps and fixed oxide traps. The dispersion of Rs is mainly attributed to contact capacitance (Cc) and contact resistance (Rc). At depletion and inversion, the frequency dispersion of C, Rp, CIL, RIL, and Rs are mainly attributed to the depletion layer capacitance (CD). The interface trap capacitance (Cit) and interface trap resistance (Rit) are not dominant for the dispersion of C, Rp, CIL, RIL, and Rs.

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