Amentoflavone-loaded nanoparticles enhanced chemotherapy efficacy by inhibition of AKR1B10.

Therapeutic nanoparticles can be combined with different anticancer drugs to achieve a synergistic therapy and avoid the limitations of traditional medicine and thus have clinical prospects for cancer. Herein, an effective nanoplatform was developed for self-assembling AMF@DOX-Fe3+-PEG nanoparticles (ADPF NPs) via the coordination of ferric ions (Fe3+), amentoflavone (AMF), doxorubicin (DOX), and PEG-polyphenol. The ADPF NPs possessed high drug loading efficiency, good stability and dispersion in water, prolonged blood circulation, and pH-dependent release, which leading to targeted drug transport and enhanced drug accumulation in the tumor. The AMF from the ADPF NPs could inhibit the expression of the Aldo-keto reductase family 1B10 (AKR1B10) and nuclear factor-kappa B p65 (NF-κB p65), which reduced the cardiotoxicity induced by DOX and enhanced the chemotherapy efficacy. This study established a new strategy of combining drug therapy with a nanoplatform. This new strategy has a wide application prospect in clinical tumor therapy.

Polyphenol-Based Paclitaxel Prodrug Self-Assembled Nanoplatform for Tumor Synergistic Therapy.

With the development of nanomedicine, studies focus on self-assembled nanoplatforms to reduce the toxicity of paclitaxel (PTX), promote the immune function at low-toxicity PTX, and achieve tumor synergistic therapy. Herein, a new nanoplatform was prepared with self-assembled 5-hydroxydopamine (DA)-PTX@tannic acid (TA)-Fe3+ nanoparticles (TDPP NPs) by consolidation of targeted DA-PTX and TA with the assistance of coordination between polyphenols and Fe3+. The polyphenol-based TDPP NPs can reduce the toxicity of PTX and thereby realize the in vitro and in vivo synergistic effect against tumors. The low-toxicity TDPP NPs can enhance the expression of CD40 immune protein. Moreover, the TDPP NPs possessed a small size (52.2±4 nm), high drug loading efficiency (95%), and stable pharmacokinetics, ensuring high tumor accumulation of TDPP NPs by enhanced permeability and retention effect. Our work sheds new light on the nanoformulation of PTX with low toxicity and synergistic therapy effect, which may find clinical applications in the future.

Myricetin-Based Self-Assembled Nanoparticles for Tumor Synergistic Therapy by Antioxidation Pathway.

Nanoplatforms are nano-scale systems that can transport different small molecular anticancer drugs or chemosensitization motif to accumulate in tumor cells without obvious side-effect in normal cells and achieve a synergistic therapy. In this paper the new self-assembled nanoparticles (NPs) merging doxorubicin (DOX) and myricetin (MYR) with ferric ions (Fe3+) and polyphenol was employed for forming the DOX@MYR-Fe3+ NP (FDMP NP). The FDMP NPs could reduce the DOX-induced toxicity in blood; and they could not cause damage to the heart and kidney tissues by the reasons that the MYR could enhance the anti-oxidation capability in normal cells, which resulted in preventing ROS-induced damage. Additionally, the FDMP NPs were characteristic of small size (37.70 ± 6.30 nm), high DOX loading efficiency (46.67 ± 1.58%), pH-controlled release and excellent stable pharmacokinetics, that inducing drug release and enhancing drug accumulation in the tumor. Moreover, the FDMP NPs could inhibit the expression of the hypoxia-inducible factor-1 α(HIF-1α) and the key angiogenesis mediator vascular endothelial growth factor (VEGF) both in vitro and in vivo, which succeed in preventing the generation of new blood vessel networks; that is the mechanism of the synergistic effect against tumors induced by FDMP NPs.