Combining histone deacetylase inhibitors (HDACis) with other therapies for cancer therapy.

Histone deacetylases (HDACs) play an important role in regulating the expression of genes involved in tumorigenesis and tumor maintenance, and hence they have been considered as key targets in cancer therapy. As a novel category of antitumor agents, histone deacetylase inhibitors (HDACis) can induce cell cycle arrest, apoptosis, and differentiation in cancer cells, ultimately combating cancer. Although in the United States, the use of HDACis for the treatment of certain cancers has been approved, the therapeutic efficacy of HDACis as a single therapeutic agent in solid tumorshas been unsatisfactory and drug resistance may yet occur. To enhance therapeutic efficacy and limit drug resistance, numerous combination therapies involving HDACis in synergy with other antitumor therapies have been studied. In this review, we describe the classification of HDACs. Moreover, we summarize the antitumor mechanism of the HDACis for targeting key cellular processes of cancers (cell cycle, apoptosis, angiogenesis, DNA repair, and immune response). In addition, we outline the major developments of other antitumor therapies in combination with HDACis, including chemotherapy, radiotherapy, phototherapy, targeted therapy, and immunotherapy. Finally, we discuss the current state and challenges of HDACis-drugs combinations in future clinical studies, with the aim of optimizing the antitumor effect of such combinations.

Rationally assembled albumin/indocyanine green nanocomplex for enhanced tumor imaging to guide photothermal therapy.

Herein, a novel phototheranostic nanocomplex that is self-assembled from bovine serum albumin (BSA) and indocyanine green (ICG) is developed for enhanced near-infrared (NIR) fluorescence imaging, which benefits the guidance on in vivo cancer photothermal therapy (PTT). The study confirms that the binding of ICG with the bind sits on the albumin will result in improved hydrolytic stability and high photoluminescence quantum yield (PLQY). The ICG loading ratio in the nanocomplex is optimized and confirms the loading ratio of 0.5% ICG to be the optimal content. The optimized ICG-BSA nanocomplex (ICG-BSA NC) possesses a higher PLQY of 16.8% than that of free ICG (2.7%). The high PLQY and efficient passive targeting ability of ICG-BSA NC help improve its in vivo tumor accumulation and NIR fluorescence imaging significantly. Under laser irradiation, efficient PTT with obvious tumor growth suppression on a triple negative breast tumor model can be observed in the ICG-BSA NC treated group.

Self-carried curcumin nanoparticles for in vitro and in vivo cancer therapy with real-time monitoring of drug release.

The use of different nanocarriers for delivering hydrophobic pharmaceutical agents to tumor sites has garnered major attention. Despite the merits of these nanocarriers, further studies are needed to improve their drug loading capacities (which are typically <10%) and reduce their potential systemic toxicity. Therefore, the development of alternative self-carried nanodrug delivery strategies without using inert carriers is highly desirable. In this study, we developed a self-carried curcumin (Cur) nanodrug for highly effective cancer therapy in vitro and in vivo with real-time monitoring of drug release. With a biocompatible C18PMH-PEG functionalization, the Cur nanoparticles (NPs) showed excellent dispersibility and outstanding stability in physiological environments with drug loading capacities >78 wt%. Both confocal microscopy and flow cytometry confirmed the cellular fluorescence "OFF-ON" activation and real-time monitoring of the Cur molecule release. In vitro and in vivo experiments clearly show that the therapeutic efficacy of the PEGylated Cur NPs is considerably better than that of free Cur. This self-carried strategy with real-time monitoring of drug release may open a new way for simultaneous cancer therapy and monitoring.