Cancer‐Targeting Functionalization of Selenium‐Containing Ruthenium Conjugate with Tumor Microenvironment‐Responsive Property to Enhance Theranostic Effects

Abstract

A mutifunctional ruthenium‐based conjugate Ru‐BSe was designed and synthesized. The Ru complex with favorable bioimaging function was covalently linked with a cancer‐targeted molecule that could be effectively internalized by the tumor to realize enhanced theranostic effects. The pH‐response of the Ru conjugate in tumor acidic microenvironment causes ligand substitution and release of therapeutic complex. This activated complex remains inert to the reducing biomolecule‐glutathione and terminally locates in mitochondria, in which it triggers oxidative stress, and activates intrinsic apoptosis. Real‐time monitoring reveals that this Ru conjugate could selectively accumulate in tumor tissue in vivo, which significantly suppresses tumor progression and alleviate the damage to normal organs, realizing the precise cancer theranosis.

A highly X-ray sensitive iridium prodrug for visualized tumor radiochemotherapy

“…The change of Bcl-2 and Bax protein expression levels in various treatments was measured by western blotting. 17 Aer various treatments, the proteins of A549 cells were collected using cell lysis buffer. The proteins were quantied using the BCA protein assay and separated by SDS-PAGE.…”

“…with a positive charge are ideal candidates for mitochondria-targeting RSs since heavy metals with high-Z are sensitive to X-rays and positively charged materials tend to accumulate in mitochondria. 16,17 Despite the fact that using lipophilic heavy metal complexes with a positive charge as RSs can well combat the deciencies of DNA-targeting RSs, the lack of visualization of tumor sites and the low bioavailability of RSs also hinder their application. Cyclometalated iridium-based (Ir, Z ¼ 77) materials would be promising candidates for the design of novel RSs with bioimaging function due to their long-lived luminescence, good light stability and also photophysical sensitivity to acidity, oxygen content or viscosity.…”

Chemosensitization of doxorubicin against lung cancer by nature borneol, involvement of TRPM8-regulated calcium mobilization

“…The integration of mitochondria membrane is regulated by the balance of pro-survival proteins, such as Bcl-2 and Bcl-xL, and pro-apoptosis protein, such as Bax and Bad. Upon apoptosis inducing signal transduction, △ψm is depleted and ultimately result in destruction of mitochondria structure [43]. This study shows that borneol combined with DOX dramatically downregulates Bcl-2/Bax protein expression to induce mitochondrial dysfunction and activate endogenous apoptosis pathway, which suggests that mitochondria-mediated pathway exhibits an important role in NB serves as a sensitizer of DOX.…”

Combination of Ruthenium Complex and Doxorubicin Synergistically Inhibits Cancer Cell Growth by Down-Regulating PI3K/AKT Signaling Pathway

“…Ruthenium-based complexes have more properties compared with platinum-based drugs, including variable oxidation states, better tumor selectivity, and similar ligand exchange kinetics (12). More importantly, ruthenium-based complexes showed mild toxicity toward normal tissues, making them promising chemotherapeutic agents (13). The application of ruthenium complex is vast because of its special structure.…”