A NIR-triggered multifunctional nanoplatform mediated by Hsp70 siRNA for chemo-hypothermal photothermal synergistic therapy.

Recently, hypothermal photothermal therapy (HPTT) seemed essential for the future clinical transformation of cancer optical therapies. However, at a lower working temperature, heat shock proteins (HSPs) seriously affect the anti-tumor effect of HPTT. This work reports a reasonable design of a dual-responsive nanoplatform for the synergistic treatment of chemotherapy and HPTT. We adopted a one-step method to wrap indocyanine green (ICG) into imidazole skeleton-8 (ZIF-8) and further loaded it with the chemotherapy drug doxorubicin (DOX). Furthermore, we introduced Hsp-70 siRNA to block the affection of HSPs at an upstream node, thereby avoiding the side effects of traditional heat shock protein inhibitors. The prepared ZIF-8@ICG@DOX@siRNA nanoparticles (ZID-Si NPs) could significantly improve the stability of siRNA to effectively down-regulate the expression of HSP70 protein during the photothermal therapy, thus realizing the pH-controlled and NIR-triggered release of the chemotherapeutical drug DOX. Moreover, tumors were also imaged accurately by ICG wrapped in ZID-Si nanoparticles. After the evaluation of the in vitro and in vivo photothermal effect as well as the anti-tumor activity, we found that the added Hsp-70 siRNA enhanced the synergistic anti-cancer activity of HPTT and chemotherapy. In summary, this work holds great potential in cancer treatment, and suggests better efficacy of synergistic chemo/HPTT than the single-agent therapy.

Cyclopropyl Scaffold: A Generalist for Marketed Drugs.

In recent decades, much attention has been given to cyclopropyl scaffolds, which commonly exist in natural products and synthetic organic molecules. Clinical drug molecules with cyclopropyl rings are an area of focus in therapeutic research due to their interesting chemical properties and unique pharmacology activity. These molecular drugs against different targets are applicable in some therapeutic treatment fields including cancer, infection, respiratory disorder, cardiovascular and cerebrovascular diseases, dysphrenia, nervous system disorders, endocrine and metabolic disorders, skin disease, digestive disorders, urogenital diseases, otolaryngological and dental diseases, and eye diseases. This review is a guide for pharmacologists who are in search of valid preclinical/clinical drug compounds where the progress, from 1961 to the present day, of approved marketed drugs containing cyclopropyl scaffold is examined.

Discovery and development of novel rhodanine derivatives targeting enoyl-acyl carrier protein reductase.

A series of rhodanine derivatives RB1-RB23 were synthesized through a two-round screening. Their Mycobacterial tuberculosis (Mtb) InhA inhibitory activity and Mtb growth blocking capability were evaluated. The most potent hit compound RB23 indicated comparable InhA inhibiton (IC50 = 2.55 µM) with the positive control Triclosan (IC50 = 6.14 µM) and Isoniazid (IC50 = 8.29 µM). Its improved growth-blocking effect on Mtb and low toxicity were attractive for further development. The docking simulation revealed the possible binding pattern of this series and picked the key interacted residues as Ser20, Phe149, Lys165 and Thr196. The 3D-QSAR model visualized the SAR discussion and hinted new information. Modifying the surroundings near rhodanine moiety might be promising attempts in later investigations.