ROS Responsive Nanoparticles Encapsulated with Natural Medicine Remodel Autophagy Homeostasis in Breast Cancer.

In photodynamic therapy (PDT), elevated reactive oxygen species (ROS) activate tumor cell protective autophagy, therefore attenuating the antitumor function of therapy. Hence, inhibition of protective autophagy in tumors can improve the antitumor effect of PDT. Herein, an innovative nanotraditional Chinese medicine system ((TP+A)@TkPEG NPs), which remodeled autophagy homeostasis, was fabricated. A photosensitizer aggregation inducing emission (AIE) and autophagy modulator triptolide (TP, an active ingredient of Tripterygium wilfordii Hook F) were encapsulated into ROS-responsive nanoparticles to improve antitumor effect of PDT in treatment of triple negative breast cancer. We proved that (TP+A)@TkPEG NPs effectively elevated intracellular ROS levels, activated ROS-responsive release of TP and inhibited the proliferation of 4T1 cells in vitro. More importantly, it sharply reduced autophagy related genes transcription and proteins expression in 4T1 cells, then promote cell apoptosis. In addition, this nanoherb therapeutic system effectively orientated to tumor sites, achieved efficient inhibition of tumor, and extended the survival time of 4T1-bearing mice in vivo. Further results confirmed that (TP+A)@TkPEG NPs remarkably inhibit the expression level of autophagy related initiation gene (becline-1) and elongation protein (light chain 3B) in tumor microenvironment and then block PDT induced protective autophagy. In brief, this system can remodel autophagy homeostasis and serve as an innovative approach for treatment of triple negative breast cancer.

Nano-traditional Chinese medicine: a promising strategy and its recent advances.

Traditional Chinese Medicine (TCM) has been applied to the prevention and treatment of numerous diseases and has an irreplaceable role in rehabilitation and health care. However, the application of TCMs is drastically limited by their defects, such as single administration, poor water solubility, low bioavailability, and weak targeting capability. Recently, nanoparticles have been extensively used in resolving pharmaceutical obstacles in consideration of their large specific surface area, strong targeting capability, good sustained-release effect, etc. In this review, we first describe the limitations of TCM ingredients and two significant forms of nanotechnology applied in TCM, nanometerization of TCMs and nano-drug delivery systems for TCMs. Then, we discuss the preparation methods of nanometerization: mechanical crushing, spray drying, and high-pressure homogenization, which have been utilized to conquer the various weaknesses of TCMs. Then, recent advances in nano-drug delivery systems for TCM ingredients are discussed, including lipid-based nanocarriers, polymeric nanoparticles, inorganic nanocarriers, hybrid nanoparticles, and TCM self-assembled nanoparticles. Finally, the future challenges and perspectives of TCM formula complexity and the limitations of nanocarriers are also discussed. Better understanding the function of nanotechnology in TCM will help to modernize Chinese medicine and broaden the application of nano-TCM in the clinic.

An NIR-responsive mesoporous silica nanosystem for synergetic photothermal-immunoenhancement therapy of hepatocellular carcinoma.

To create a more precise, efficient imaging and therapeutic strategy is a big challenge for the current treatment of hepatocellular carcinoma (HCC). Photothermal therapy (PTT) has attracted enormous attention due to its non-invasive property and precise spatial and temporal control. Here, we developed a strategy to realize superior imaging performance and treatment, utilizing an indocyanine green (ICG) and sorafenib (S) co-loaded mesoporous silica nanosystem for synergetic PTT/immuno-enhanced therapy. We proved that (ICG+S)@mSiO2 could be easily endocytosed by H22 cells, carried out outstanding real-time fluorescence imaging, and enhanced cytotoxicity abilities by near-infrared radiation (NIR) in vitro. Moreover, (ICG+S)@mSiO2 also had excellent fluorescence imaging ability, displayed a remarkable photothermal tumor killing effect and immune enhancement capability under 808 nm irradiation in an H22 tumor-bearing mice model, without apparent adverse effects in other organs. This study provides a new strategy for the development of a PTT/immuno-enhanced synergistic theranostic nanosystem of HCC.