Gas Therapy: An Emerging “Green” Strategy for Anticancer Therapeutics

Abstract

As an emerging area, gas therapy has attracted more and more attention in treating many diseases including cancer. The fabrication of stimuli-responsive delivery systems with on-demand release behavior is very promising for precision gas therapy, which can obtain optimal therapeutic performance without gas poisoning risks. In this review, the authors introduce the recent progress in the preparation of different kinds of gas carriers for efficient delivery of gaseous molecules (NO, H 2 S, CO, O 2 ). Particularly, in order to achieve targeted accumulation of gaseous molecules in tumor tissues, gaseous molecules-integrated nanoparticles were constructed. Most importantly, by combination of gas therapy with other therapeutic modalities such as chemotherapy, photodynamic therapy (PDT), and radiotherapy, various multifunctional nanocarriers have been designed for synergistic cancer therapy. Especially, the recent developments of multifunctional gas-carrying nanocarriers for synergistic cancer therapy are discussed in detail.

Emerging Delivery Strategies of Carbon Monoxide for Therapeutic Applications: from CO Gas to CO Releasing Nanomaterials

“…Compared with external stimuli‐induced CO release, the release of CO triggered by specific pathologic microenvironment (such as H 2 O 2, glutathione, cysteine, pH and enzyme) is not limited by the penetration depth and thus is more advantageous to tissue‐specific CO therapy …”

“…As is known to all, the concentration of H 2 O 2 in tumor is much higher than that in normal tissue . The H 2 O 2 ‐responsive CO release behavior of manganese carbonyl (MnCO) was first discovered by Jin et al The high concentration of H 2 O 2 in tumor was catalytically decomposed into strongly oxidative hydroxide free radicals by Mn 2+ ions through a new Fenton‐like reaction.…”

“…Then, the hydroxide free radicals efficiently oxidized and competitively coordinated with the Mn center in MnCO, eventually leading to the release of CO from MnCO ( Figure a). Additionally, high concentration thiol‐containing compounds such as glutathione (GSH) and cysteine can also be utilized as effective stimuli for CO release in cellular . For instance, Gao et al have reported a GSH‐responsive dual‐iron hexacarbonyl compound (TG‐FeCORM) which could be used to the site‐specific CO release in cancer cells.…”

“…Moreover, the anti‐inflammatory effect of CO release from TG‐FeCORM was verified by detecting the expression level of inflammatory cytokines in LPS‐stimulated HeLa cells. As another thiol‐containing compound, cysteine has also shown to be an internal stimulus for CO delivery and is especially effective for Ru‐based CORMs . For boranocarbonate compounds (Na[H 3 BCO 2 H]), the rate of CO release was both pH‐ and temperature‐dependent and the half‐life of CO release ranged from 2.5 min (pH = 5.5) to 21 min (pH = 7.4) at 37 °C .…”

“…Take chemotherapeutic drugs for tumor treatment as an example. Chemotherapy usually suffers from drug resistance in cancer therapy, whereas gaseous CO molecules do not induce drug resistance because it can easily diffuse into the tumor tissue and lead to cell apoptosis following CO‐responsive metabolic exhaustion . Furthermore, CO could not only amplify tumor cell death when treated in combination with chemotherapeutic drugs but also exert cytoprotective function and protect normal cells against chemotherapeutic agent‐induced cell toxicity .…”