Intratumoral H₂O₂-triggered release of CO from a metal carbonyl-based nanomedicine for efficient CO therapy

Abstract

A new HO-responsive nanomedicine for CO therapy is constructed by effectively encapsulating the hydrophobic manganese carbonyl prodrug into an advanced hollow mesoporous silica nanoparticle carrier to realize the intratumoral HO-triggered release of CO and selective killing of tumour cells rather than normal cells, exhibiting high in vitro and in vivo efficacies of CO therapy.

Intelligent Metal Carbonyl Metal–Organic Framework Nanocomplex for Fluorescent Traceable H2O2‐Triggered CO Delivery

“…From the BET results (Figure S1 in the Supporting Information), the MnCO loading has caused the micropores of the Ti‐MOF to be blocked and the specific surface area sharply drops to 432 m 2 g −1 , reflecting that the MnCO prodrug had been loaded into the micropores of the Ti‐MOF. According to the difference in the absorbance of MnCO solutions before and after loading and the Beer law, the MnCO loading capacity of the Ti‐MOF is measured to be as high as 532 mg g −1 , which is higher than that of inorganic carriers . Such a high drug capacity could be attributed to the high surface area of the Ti‐MOF and the coordination between MnCO and the Ti‐MOF.…”

“…The controlled release behavior and release monitoring performance of MnCO@Ti‐MOF were further investigated. In our recent report, manganese carbonyl has been identified as a H 2 O 2 ‐responsive CO‐releasing prodrug by a Fenton‐like reaction . In this work, we further testified the H 2 O 2 ‐responsive CO release behavior of the constructed MnCO@Ti‐MOF and meanwhile, the fluorescence recovery profile during the CO release was also monitored under tumor microenvironment‐simulated conditions composed of pH 7.4 phosphate‐buffered saline solution (PBS) with different concentrations of H 2 O 2 .…”

“…OH radicals under the catalysis of MnCO by a Fenton‐like reaction, and the strongly oxidative . OH radicals further oxidize and competitively coordinate with the Mn center, thereby causing the release of CO from MnCO@Ti‐MOF . Under the same conditions, the fluorescence intensity was quantitatively measured in real time by using a fluorescence spectrometer with an excitation of λ =350 nm.…”

“…Unfortunately, either the lack of controllability or the presence of phototoxicity accompanied by the limited penetrability troublesomely hinders the practical utility. By comparison, the endogenous triggering of CO release by the tumor microenvironment (TME, such as acidity, redox property, over‐expressed H 2 O 2 ) is superior owing to no limitation of the penetration depth, and a more focused and tumor‐specific CO release, but there has not been a related breakthrough so far. Moreover, the integration of TME‐responsive drugs with advanced nanocarriers is also highly desired to achieve a targeted delivery, controlled release, and release monitoring for CO therapy of cancer .…”

Physical‐, chemical‐, and biological‐responsive nanomedicine for cancer therapy

“…Due to the tumor environment is also like inflammatory tissue, oxidation responsiveness was based on hypoxic environment induced by the ROS accumulation (Hua et al, ; W. Huang et al, ; Wan, Zeng, Cheng, & Zhang, ). In 2017, Qian et al identified manganese carbonyl as a novel H 2 O 2 ‐responsive CO release molecule and constructed MnCO@hMSN anti‐tumor nanoparticles by hollow mesoporous silica nanoparticles co‐loaded with Mn nanoparticle and CO prodrug (Z. Jin, Wen, Xiong, et al, ). The fabricated MnCO@hMSN nanosystem exhibited CO on‐demand release triggered by H 2 O 2 in intracellular microenvironment and presented high anti‐tumor efficacy in vitro and in vivo.…”