H ₂ S-Activated “One-Key Triple-Lock” Bis-Metal Coordination Network for Visualizing Precise Therapy of Colon Cancer

Abstract

Colon cancer is the third most common malignancy and the fourth most prevalent cause of death worldwide. Unfortunately, current cancer treatment approaches suffer from low specificity toward colon cancers and lack of facile imaging method to monitor a real-time therapeutic process, usually resulting in severe toxicity to normal tissues. Thus, to achieve precise therapy for colon cancer, we developed a "one-key triple-lock" bis-metal ultrathin coordination network (Gd/Cu-nanosheets) as the first H 2 S-unlocked molecular dipoles with activatable fluorescence, magnetic resonance imaging (MRI), and photodynamic effect. Notably, within noncancerous tissues, Cu ions can lock up MRI signal, fluorescent emission, and 1 O 2 generation of molecular dipoles (Gd-porphyrins). Under the trigger of endogenous H 2 S overexpressed colon cancer model (HCT116), the loss photodynamic effect of the as-disassembled Gd-porphyrin was recovered for efficient and potent killing of colon cancer cells in vivo, with minimization of toxic side effect toward normal tissue. By combining the complementary advantages of bimodal MRI/ fluorescence imaging, Gd/Cu-nanosheets enabled high-specificity visualization of colon cancer in living cells and in vivo upon activation of H 2 S. Moreover, a good correlation between the fluorescence intensity of Gd/Cu-nanosheets and cancer inhibition rates afforded the ability to self-report cancer therapeutic outcomes, thereby providing a potentially powerful tool for personalized and precise treatment of colon cancer.

ER-Targeting Cyanine Dye as an NIR Photoinducer to Efficiently Trigger Photoimmunogenic Cancer Cell Death

“…Hypericin utilizes the visible-light energy to cause massive production ROS and inducts of oxidative stress with damage to ER membranes. However, the visible light is not as useful as near-infrared (NIR) in in vivo therapy. − Until now, noble metals and heavy-atom-containing compounds have played an important role in clinical trials, which have been viewed as successful and well-known ROS generators. − By comparison, organic heavy-atom-free photosensitizers give design challenges but have received extensive attention in the biomedical field because of their low-cost synthesis, easy processability, and excellent biocompatibility. − If a heavy-atom-free chromophore could be well-designed to photogenerate ROS as imagined, it might be integrated to become an ideal ICD photoinducer. Furthermore, developing ER-localizable NIR photosensitizers (ER-PSs) must be the most preeminent protocol to explore type II ICD photoinducers.…”

Advanced Light Source Analytical Techniques for Exploring the Biological Behavior and Fate of Nanomedicines

“…One aspect of nanomedicines that remains poorly understood is the true physiochemical behavior of nanostructures inside the dynamic biological environment. The biological behavior and fate of nanomedicines, ,− and the information underlying nanomaterial–biology (nano–bio) interactions, − spatiotemporal relationships among networks of nanoparticles (NPs), − their metabolic products, ,− and cell components must be defined. Understanding these relationships will allow us to grasp how nanomedicines interact with their surrounding biological environments and how variations in nanoformulations manifest protein corona characteristics as well as cellular responses, such as oxidative stress, genetic damage, and toxicity.…”

H2S‐Responsive Small‐Molecule Nanocarriers for Drug Delivery to Colorectal Tumors

“…[13][14][15][16] Several studies have demonstrated the superiority of H 2 S as an internal stimulus for drug delivery. [17][18][19][20][21][22][23][24][25][26][27][28] For instance, copper sulfide (CuS) formation via the reaction between H 2 S and copper ions was utilized to release copper-coordinated doxorubicin (DOX) from protein nanocages. [29] In situ formation of CuS was used for activating photothermal therapy and triggering drug release from liposomes [30] or metal-organic framework.…”