Melanin-Integrated Structural Color Hybrid Hydrogels for Wound Healing.

Hydrogel patches have outstanding values in wound treatment; challenges in this field are concentrated on developing functional and intelligent hydrogel patches with new antibacterial strategies for improving healing process. Herein, a novel melanin-integrated structural color hybrid hydrogel patches for wound healing is presented. Such hybrid hydrogel patches are fabricated by infusing asiatic acid (AA)-loaded low melting-point agarose (AG) pregel into the melanin nanoparticles (MNPs)-integrated fish gelatin inverse opal film. In this system, MNPs not only impart the hybrid hydrogels with properties of photothermal antibacterial and antioxidant, but also improve the visibility of structural colors by providing an inherent dark background. Besides, the photothermal effect of MNPs under near-infrared irradiation can also trigger liquid transformation of AG component in hybrid patch, resulting in the controllable release of its loaded proangiogenic AA. Attracting, this drug release induced refractive index variations in the patch can be detected as visible structural color shifting, which can be used to monitor their delivery processes. Benefiting from these features, the hybrid hydrogel patches are demonstrated to achieve excellent therapeutic effects for in vivo wound treatment. Thus, it is believed that the proposed melanin-integrated structural color hybrid hydrogels are valuable as multifunctional patches for clinical applications.

Rocket-Inspired Effervescent Motors for Oral Macromolecule Delivery.

Oral administration is among the most convenient ways with good patient compliance for drug delivery; while it remains a challenge to achieve desirable bioavailability of most macromolecules due to the complex gastrointestinal barriers. Here, inspired by the structure and function of rocket, a novel micromotor delivery system is presented with scaled-down rocket-like architecture and effervescent-tablets-derived fuel for efficient oral macromolecule delivery by penetrating intestinal barrier. These rocket-inspired effervescent motors (RIEMs) are composed of sharp needle tips for both loading cargoes and efficient penetrating, and tail wings for loading effervescent powders and avoiding perforation. When exposed to a water environment, the effervescent fuel generates intensive CO2 bubbles to propel the RIEMs to move at high speed. Thus, the RIEMs with their sharp tip can inject into the surrounding mucosa for effective drug release. Furthermore, benefiting from their tail-wing design, perforation can be effectively avoided during the injection process, ensuring the safety of the RIEMs in gastrointestinal active delivery. Based on these advantages, it is demonstrated that the RIEMs can efficiently move and stab into the intestinal mucosa for insulin delivery, exhibiting efficacy in regulating blood sugar glucose in a diabetic rabbit model. These features indicate that these RIEMs are versatile and valuable for clinical oral delivery of macromolecules.

Rotary Structural Color Spindles from Droplet Confined Magnetic Self-Assembly.

Structural colors materials are profoundly explored owing to their fantastic optical properties and widespread applications. Development of structural color materials bearing flexible morphologies and versatile functionalities is highly anticipated. Here, a droplet-confined, magnetic-induced self-assembly strategy for generating rotary structural color spindles (SCSPs) by fast solvent extraction is proposed. The as-prepared SCSPs exhibit an orderly close-packed lattice structure, thus appearing brilliant structural colors that serve as encoding tags for multiplexed bioassays. Besides, benefitting from the abundant specific surface area, biomarkers can be labeled on the SCSPs with high efficiency for specific detection of analytes in clinical samples. Moreover, the directional magnetic moment arrangement enables contactless magnetic manipulation of the SCSPs, and the resultant rotary motions of the SCSPs generates turbulence in the detection solution, thus significantly improving the detection efficiency and shortening the detection time. Based on these merits, a portable point-of-care-testing strip integrating the rotary SCSPs is further constructed and the capability and advantages of this platform for multiplexed detection of tumor-related exosomes in clinical samples are demonstrated. This study offers a new way for the control of bottom-up self-assembly and extends the configuration and application values of colloidal crystal structural colors materials.

Freeze-derived heterogeneous structural color films.

Structural colors have a demonstrated value in constructing various functional materials. Efforts in this area are devoted to developing stratagem for generating heterogeneous structurally colored materials with new architectures and functions. Here, inspired by icing process in nature and ice-templating technologies, we present freeze-derived heterogeneous structural color hydrogels with multiscale structural and functional features. We find that the space-occupying effect of ice crystals is helpful for tuning the distance of non-close-packed colloidal crystal nanoparticles, resulting in corresponding reflection wavelength shifts in the icing area. Thus, by effectively controlling the growth of ice crystals and photo-polymerizing them, structural color hydrogels with the desired structures and morphologies can be customized. Other than traditional monochromatic structure color hydrogels, the resultant hydrogels can be imparted with heterogeneous structured multi-compartment body and multi-color with designed patterns through varying the freezing area design. Based on these features, we have also explored the potential value of these heterotypic structural color hydrogels for information encryptions and decryptions by creating spatiotemporally controlled icing areas. We believe that these inverse ice-template structural color hydrogels will offer new routes for the construction and modulation of next generation smart materials with desired complex architectures.

Olaparib hydroxamic acid derivatives as dual PARP and HDAC inhibitors for cancer therapy.

Olaparib was the first PARP inhibitor approved by the FDA for patients with BRCA-mutated ovarian cancer. Recent studies have demonstrated enhanced anticancer effects of combination therapy consisting of olaparib and HDAC inhibitors. Herein, based on rational drug design strategy, hydroxamic acid derivatives of olaparib were constructed as dual PARP and HDAC inhibitors. These hybrid compounds showed potent inhibitory activities against PARP1/2 and HDAC1/6 with IC50 values in the nanomolar range. Furthermore, compound P1 exhibited broad-spectrum antiproliferative activities in selected human cancer cell lines. Specially, P1 showed more potent activity than olaparib and SAHA in cancer cells MDA-MB-231, HCC1937 and Raji, and 4.1-fold less cytotoxicity compared with SAHA to normal cells MCF-10A. Further mechanism study indicated that P1 could induce the cleavage of PARP and the hyperacetylation of histones, increase the expression of DNA damage biomarker γ-H2AX, decrease the level of BRCA1 and RAD51, and regulate tumor cell growth and apoptosis through modulating both mitochondrial- and death receptor-mediated pathways. Therefore, our study suggested that compounds targeting PARP and HDAC concurrently might be a practical approach for cancer therapy.

Design, synthesis and anticancer potential of NSC-319745 hydroxamic acid derivatives as DNMT and HDAC inhibitors.

DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) are important epigenetic targets during anticancer drug development. Recent study indicates that DNMT inhibitors and HDAC inhibitors display synergistic effects in certain cancers, therefore, development of molecules targeting both DNMT and HDAC is of therapeutic advantage against these cancers. Based on the structure of DNMT inhibitor NSC-319745 and the pharmacophore characteristics of HDAC inhibitors, a series of hydroxamic acid derivatives of NSC-319745 were designed and synthesized as DNMT and HDAC multifunctional inhibitors. Most compounds displayed potential DNMT inhibitory potency and potent HDAC inhibitory activity, especially compound 15a showed much better DNMT1 inhibitory potency than NSC-319745, and inhibited HDAC1, HDAC6 with IC50 values of 57, 17 nM, respectively. Furthermore, the synthesized compounds exhibited significant cytotoxicity against human cancer cells K562 and U937. Further mechanistic studies demonstrated that 15a treatment in U937 increased histones H3K9 and H4K8 acetylation, prompted P16 CpG islands demethylation and upregulated P16 expression, regulated apoptosis-related protein expression on the cellular level and induced remarkable U937 apoptosis. Moreover, genotoxicity of representative compounds was evaluated. In summary, our study provided a practical drug design strategy targeting multiple enzymes, and 15a represents a novel and promising lead compound for the development of novel epigenetic inhibitors as antitumor agents.