Human Serum Albumin-Platinum(II) Agent Nanoparticles Inhibit Tumor Growth Through Multimodal Action Against the Tumor Microenvironment.

To overcome the limitations of traditional platinum (Pt)-based drugs and further improve the targeting ability and therapeutic efficacy in vivo, we proposed to design a human serum albumin (HSA)-Pt agent complex nanoparticle (NP) for cancer treatment by multimodal action against the tumor microenvironment. We not only synthesized a series of Pt(II) di-2-pyridone thiosemicarbazone compounds and obtained a Pt(II) agent [Pt(Dp44mT)Cl] with significant anticancer activity but also successfully constructed a novel HSA-Pt(Dp44mT) complex nanoparticle delivery system. The structure of the HSA-Pt(Dp44mT) complex revealed that Pt(Dp44mT)Cl binds to the IIA subdomain of HSA and coordinates with His-242. The HSA-His242-Pt-Dp44mT NPs had an obvious effect on the inhibition of tumor growth, which was superior to that of Dp44mT and Pt(Dp44mT)Cl, and they had almost no toxicity. In addition, the HSA-His242-Pt-Dp44mT NPs were found to kill cancer cells by inducing apoptosis, autophagy, and inhibiting angiogenesis.

Design of a binary metal micron grating and its application in near-infrared hot-electron photodetectors.

Metal plasmonic nano-gratings possess a high absorption ability and exhibit potential applications in sensing, hot-electron photodetection, metasurfaces, etc. However, the fabrication techniques of high-quality nano-gratings are challenging. In this article, a binary metal micron grating for near-infrared hot-electron photodetectors (HEPDs) is designed in which the surface plasmons are excited by high-diffraction-order modes. The high-diffraction-order micron grating can be fabricated by conventional lithography and has a significantly higher tolerance in the grating parameters than a nano-grating. The range of absorption greater than 70% is ∼3 times that of a nano-grating. Moreover, an interesting relationship between the resonant wavelength and the grating duty cycle is found. When the high-diffraction-order micron grating is applied in metal-insulator-metal HEPDs, a high zero-biased responsivity of 0.533 mA/W is achieved.

Designing a multitarget In(III) compound to overcome the resistance of lung cancer cells to cisplatin.

Designing novel anticancer non-platinum metal agents is fully challenging. Herein, a series of little-known indium (In) 2-acetylpyridine thiosemicarbazone compounds as potential anticancer agents were designed, synthesized, and characterized. The hydrogen atoms at the N-4 position with the alkyl of the In compounds significantly increased cellular uptake and cytotoxicity. In(III) compounds showed significantly higher cytotoxicity toward cisplatin-resistant cell lines than cisplatin. More importantly, C4 greatly inhibited A549DDP tumor growth in a vaccinated mouse model. C4 exerted cytotoxic effects via a multitarget mechanism. First, it activated p53 and blocked the cell cycle at the S phase, which then led to weak expression levels of cyclin and related kinases and upregulation of the expression levels of cyclin-dependent kinase inhibitors. C4 also depolarized the mitochondrial membrane potential and regulated the expression of the Bcl-2 family, which then released cyt-c and activated caspase-3/8/9 to execute apoptotic pathways. Then, it inhibited telomerase through the inhibition of the expression of the c-Myc regulator gene and expression of the human telomerase reverse transcriptase. Furthermore, C4 showed excellent antimetastatic activity.