Biomimetic synthesis of 2D ultra-small copper sulfide nanoflakes based on reconfiguration of the keratin secondary structure for cancer theranostics in the NIR-II region.

Two-dimensional transition metal dichalcogenides have attracted widespread attention in cancer theranostics due to their high specific surface area and excellent photothermal conversion properties. However, their dimensions and biodegradability have limited the exploration of the therapeutic properties of transition metal dichalcogenides. Herein, we explore the mechanism of the keratin α-helix-to-random coil transition, as an actuation mechanism for the controllable design and precise synthesis of two-dimension copper sulfide nanoflakes (CuS NFs) with high absorption in the NIR-II window. Upon mixing keratin and Cu2+, the hydrogen bonds that maintain the α-helix are broken by copper ions to form biuret coordination, while the structure of the α-helix is transformed into a random coil, providing a more scalable space for the growth of CuS NFs. The CuS NFs prepared in this way possess the great advantages of outstanding uniformity, size controllability, and biodegradability. Importantly, the CuS NFs in the NIR-II window show an excellent photothermal conversion efficiency (32.9%) and extraordinary photoacoustic signal. This work updates the fabrication of two-dimensional transition metal dichalcogenides and greatly enhances their competitiveness in the area of cancer theranostics in the NIR-II region, and provides significant theoretical and practical opportunities for the development of keratin using biomimetic synthesis.

PEGylated Indium Nanoparticles: A Metallic Contrast Agent for Multiwavelength Photoacoustic Imaging and Second Near-Infrared Photothermal Therapy.

Indium, a low melting point metal, is well-known for constructing eutectic gallium-indium liquid metal. However, unlike liquid metal nanoparticles, the biomedical applications of metallic indium nanoparticles (In NPs) remain in their infancy. Herein, an ultrasound-assisted liquid-reduction synthesis strategy was developed to prepare PEGylated In NPs, which were then used as a high-performance contrast agent for enhancing multiwavelength photoacoustic imaging and second near-infrared (NIR-II) photothermal therapy of the 4T1 breast tumor. The obtained In NPs depicted remarkable optical absorption from the first near-infrared (NIR-I) to NIR-II region and a high photothermal conversion efficiency of 41.3% at 1064 nm, higher than the majority of conventional NIR-II photothermal agents. Upon injection into the tumor, the photoacoustic intensities of the tumor section post-injection were obviously increased by 2.59-, 2.62-, and 4.27-fold of those of pre-injection by using excitation wavelengths of 750, 808, and 970 nm, respectively, depicting an excellent multiwavelength contrast capability of photoacoustic imaging. In addition, efficient ablation of the 4T1 tumor was achieved through the photothermal performance of PEGylated In NPs under NIR-II laser irradiation. Importantly, as the widely used element in the clinic, In NPs were highly biocompatible in vitro and in vivo. Therefore, this work pioneered the biomedical applications of PEGylated In NPs for cancer diagnosis and treatment.