Manganoporphyrin-Polyphenol Multilayer Capsules as Radical and Reactive Oxygen Species (ROS) Scavengers

Abstract

Local modulation of oxidative stress is crucial for a variety of biochemical events including cellular differentiation, apoptosis, and defense against pathogens. Currently employed natural and synthetic antioxidants exhibit a lack of biocompatibility, bioavailability, and chemical stability, resulting in limited capability to scavenge reactive oxygen species (ROS). To mediate these drawbacks, we have developed a synergistic manganoporphyrin-polyphenol polymeric nanothin coating and hollow microcapsules with efficient antioxidant activity and controllable ROS modulation. These materials are produced by multilayer assembly of a natural polyphenolic antioxidant, tannic acid (TA), with a synthesized copolymer of polyvinylpyrrolidone containing a manganoporphyrin modality (MnP-PVPON) which mimics the enzymatic antioxidant superoxide dismutase. The redox activity of the copolymer is demonstrated to dramatically increase the antioxidant response of MnP-PVPON/TA capsules versus unmodified PVPON/TA capsules through reduction of a radical cationic dye and to significantly suppress the proliferation of superoxide via cytochrome C competition. Inclusion of MnP-PVPON as an outer layer enhances radical-scavenging activity as compared to localization of the layer in the middle or inner part of the capsule shell. In addition, we demonstrate that TA is crucial for the synergistic radical-scavenging activity of the MnP-PVPON/TA system which exhibits a combined superoxide dismutase-like ability and catalase-like activity in response to the free radical superoxide challenge. The MnP-PVPON/TA capsules exhibit a negligible, 8% loss of shell thickness upon free radical treatment, while PVPON/TA capsules lose 39% of their shell thickness due to the noncatalytic free-radical-scavenging of TA, as demonstrated by small angle neutron scattering (SANS). Finally, we have found the manganoporphyrin-polyphenol capsules to be nontoxic to splenocytes from NOD mice after 48 h incubation. Our study illustrates the strong potential of combining catalytic activity of manganoporphyrins with natural polyphenolic antioxidants to design efficient free-radical-scavenging materials that may eventually be used in antioxidant therapies and as free radical dissipating protective carriers of biomolecules for biomedical or industrial applications.

<p>Multifunctional Hf/Mn-TCPP Metal-Organic Framework Nanoparticles for Triple-Modality Imaging-Guided PTT/RT Synergistic Cancer Therapy</p>

“…Importantly, the combination of PTT and RT showed strongly significant cytotoxicity compared with either treatment alone. In addition to the heating and ionization effects, according to previous studies, 16,45 the high cytotoxicity of fHMNM caused by PTT and RT may be attributed to the following reasons: the Mn-TCPP linker in fHMNM decomposes endogenous H 2 O 2 to O 2 , which prevents the repair of DNA damaged by free radicals through the "oxygen fixation hypothesis"; 46 the excited triplet state of the Hf 6 cluster can transfer energy directly to ground-state O 2 to generate singlet oxygen 1 O 2 , which leads to lethal damage to cells by damaging various cell membranes. 47 To confirm the above statements, the ability of fHMNM to catalyse H 2 O 2 to produce O 2 in vitro was assessed.…”

Polymer Capsules with Hydrophobic Liquid Cores as Functional Nanocarriers

“…The unique permeability properties of the capsule shells make these capsules excellent nano and micro reaction chambers for performing enzymatically catalyzed reactions [ 186 , 187 , 188 , 189 ]. The multilayer shells of capsules are semipermeable: permeable for small solutes; hence, the substrate and products of enzymatic reaction could permeate through the capsule wall while the enzymes are located inside and could be protected against high molecular weight inhibitors [ 189 , 190 ].…”

Multilayer capsules made of weak polyelectrolytes: a review on the preparation, functionalization and applications in drug delivery

“…Catalase enzyme encapsulated in the capsules was used to prevent oxidative stress in an in vitro inflammation model depicting that the PE shell can make encapsulated enzymes more stable compared to free enzymes. The capsules made of PVP copolymer containing a manganoporphyrin modality (MnP-PVP) and TA can mimic enzymatic antioxidant superoxide dismutase-like and catalase-like activity for efficient free radical scavenging [189]. The schematic illustration of the formation of the capsules is depicted in Figure 8a.…”

“…The multilayers have also proved to be efficient in vascular therapies for the development of suitable grafts for repairing damaged vessels or arteries [193]. [189], copyright 2017 American Chemical Society and the images in b,c were adapted and reprinted with permission from [190], copyright 2019 American Chemical Society. Further permissions related to the material excerpted should be directed to the American Chemical Society.…”