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Dihydroartemisinin (DHA), a plant-derived natural product, has recently been proven to be an effective therapeutic agent for cancer treatment. Nevertheless, the poor water solubility and low bioavailability of DHA seriously impede its clinical applications. Herein, a simple and green strategy based on the self-assembly of DHA was developed to synthesize carrier-free nanoparticles (NPs). The resulting nanodrug (DHA NPs) was formed by the self-assembly of DHA molecules viahydrogen bonding and hydrophobic interactions. The DHA NPs exhibited a near-spherical morphology with narrow size distribution, favorable drug encapsulation efficiency (>92%), excellent stability, and on-demand drug release behavior. Furthermore, the in vitroand in vivoexperiments revealed that the DHA NPs exhibited significantly higher therapeutic efficacy than the DHA equivalent. In addition, we further explored the potential molecular mechanism of the DHA NPs by utilizing RNA-seq technology and western blotting analysis, which demonstrated that the p53 signaling pathway plays a crucial part in the process of inhibiting tumor cell growth and inducing apoptosis. This work not only reveals the rationale for developing pure nanodrugs viathe self-assembly of natural small molecules for oncotherapy but also the investigation of the antitumor mechanism and provides novel theoretical support for the clinical usage of DHA.

Cancer phototheranostics that combines diagnosis with phototherapy has emerged as a new mode of precise treatment. Nevertheless, taking highly effective phototheranostics into consideration, it is still a tremendous challenge to design multifunctional photothermal agents (PTAs) that combine the features of intensive near-infrared (NIR) absorption/emission, high photothermal conversion efficiency (PCE) and preferable tumor accumulation. Herein, seeking a convenient method to facilitate absorption red-shift, promote the accumulation of drugs in tumors and heighten the PCE appears to be particularly important for cancer theranostics. In this work, heavy-atom-free boron dipyrromethene (BODIPY) was assembled with F127 to fabricate ultra-small J-aggregated nanoparticles (named as BNPs). Compared to free BODIPY, BNPs exhibited 63 nm redshifted absorption, deep-tissue fluorescence imaging, enhanced cellular uptake, preferable tumor accumulation, elevated PCE, excellent photothermal stability and water dispersibility. In vivoexperiments demonstrated that BNPs could behave as high-performance tumor fluorescent imaging probes and antitumor PTAs to conduct NIR imaging-guided PTT. This work offers a novel J-aggregated framework on developing robust diagnostic and therapeutic agents.

The NIR dye cyanine (Cy) is one of the most significant phototherapy agents (PTAs) due to its strong NIR absorbance, high thermal conversion capacity and good safety. However, its clinic application is seriously limited owing to its inherent properties as an organic dye, including low solubility, poor selectivity, and fast clearance. Thus, herein, we embed Cy into the zeolitic imidazolate framework-8 (Cy@ZIF-8) for antitumor photothermal therapy (PTT). The obtained Cy@ZIF-8 NPs not only have good water solubility and excellent photostability, but also exhibit strong NIR absorbance and great photothermal conversion efficiency. Especially, the Cy@ZIF-8 NPs efficaciously inhibit tumor growth and possess outstanding NIR imaging capacity both in vitroand in vivo. This work demonstrates the theranostic value of Cy@ZIF-8 NPs for imaging-guided PTT therapy, and also encourages the further study of other PTAs@ZIF-8 composites for better anticancer PTT.