Tumor Customized 2D Supramolecular Nanodiscs for Ultralong Tumor Retention and Precise Photothermal Therapy of Highly Heterogeneous Cancers.

Target therapy for highly heterogeneous cancers represents a major clinical challenge due to the lack of recurrent therapeutic targets identified in these tumors. Herein, the authors report a tumor-customized targeting photothermal therapy (PTT) strategy for highly heterogeneous cancers, by which 2D supramolecular self-assembled nanodiscs are modified with tumor-specific binding peptides identified by phage display techniques. Taking osteosarcoma (OS) as a model heterogeneous cancer, an OS targeting peptide (OTP) is first selected after biopanning and is demonstrated to successfully bind to this heterogeneous cancer cells/tissues. Successful conjugation of OTP to heptamethine cyanine (Cy7)-based 2D nanodiscs Cy7-TCF (2-dicyanomethylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran,TCF) enables the 2D nanodiscs to specifically target the heterogeneous tumor. Notably, a single dose injection of this targeted nanodisc (T-ND) not only effectively induces enhanced photothermal tumor ablation under near-infrared light, but also exhibits sevenfold increase of tumor retention time (more than 24 days) compared to generic nanomedicine. Thus, the authors' findings suggest that the combination of phage display-based affinity peptides selection and 2D supramolecular nanodiscs leads to the development of a platform technology for highly heterogeneous cancers precise therapy, offering specific tumor targeting, ultralong tumor retention, and precise PTT.

Coating of Epimedii Folium Water Extract onto TiO2 Nanotube Surfaces Promotes Differentiation and Proliferation of Osteoblasts.

The surface modification of titanium is effective in promoting osseointegration and is widely used in the treatment of bone diseases. Epimedii Folium (EF) plays an important role in the treatment of metabolic bone diseases. However, few studies have so far been reported on their combined use in such treatments. In the present study, EF water extract was coated onto the surface of TiO2 nanotubes (TNT) by electrochemical anodization to obtain EF-TNT. Through analysis of surface morphology characteristics, it was demonstrated that EF was successfully coated on the surface of TiO2 nanotubes. In vitro drug release data suggested that the quantity of EF water extract released was a significant quantity over 4 days, reaching a total of 80%, the release continuing in total for approximately 2 weeks. By using scanning electron microscopy and immunofluorescent staining, it was found that, EF-TNT more strongly promoted adhesion, proliferation, and differentiation of MC3T3-E1 osteoblasts compared with Ti and TNT. Quantitative reverse transcript polymerase chain reaction (qRT-PCR) analysis indicated that the expression of key genes for proliferation and differentiation of osteoblasts, such as COL1a1, ALP, OPN, and Runx2, were up-regulated by EF-TNT. Network pharmacology analysis suggested that EF water extract not only regulated the proliferation and differentiation of osteoblasts but also caused a regulatory effect on osteoclasts via multiple signaling pathways, such as RANKL-RANK-induced signaling and TGF-ß signaling. These findings indicate that the EF-TNT promotes differentiation and proliferation of osteoblasts, and represents considerable potential for use in clinical applications.