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Recent Advances in ROS-Scavenging Metallic Nanozymes for Anti-Inflammatory Diseases: A Review
MOHAPATRA ADITYANARAYAN,박인규 전남대학교 의과학연구소 2023 CMJ Vol.59 No.1
Oxidative stress and dysregulated inflammatory responses are the hallmarks of inflammatory disorders, which are key contributors to high mortality rates and impose a substantial economic burden on society. Reactive oxygen species (ROS) are vital signaling molecules that promote the development of inflammatory disorders. The existing mainstream therapeutic approaches, including steroid and non-steroidal anti-inflammatory drugs, and proinflammatory cytokine inhibitors with anti-leucocyte inhibitors, are not efficient at curing the adverse effects of severe inflammation. Moreover, they have serious side effects. Metallic nanozymes (MNZs) mimic the endogenous enzymatic process and are promising candidates for the treatment of ROS-associated inflammatory disorders. Owing to the existing level of development of these metallic nanozymes, they are efficient at scavenging excess ROS and can resolve the drawbacks of traditional therapies. This review summarizes the context of ROS during inflammation and provides an overview of recent advances in metallic nanozymes as therapeutic agents. Furthermore, the challenges associated with MNZs and an outline for future to promote the clinical translation of MNZs are discussed. Our review of this expanding multidisciplinary field will benefit the current research and clinical application of metallic-nanozyme-based ROS scavenging in inflammatory disease treatment.
REVURIVISHNU,먼달,MOHAPATRA ADITYANARAYAN,Rajendrakumar Santhosh Kalash,Surwase Sachin S.,Park In-kyu,Park Jooho,이용규 한국약제학회 2022 Journal of Pharmaceutical Investigation Vol.52 No.6
Purpose Here, we present the fabrication of a novel molybdenum-based, synthetic blue nano-enzyme (Synz) as an in situ oxygenic catalase mimic for the reduction of H2O2 and the detection of hydrogen peroxide ( H2O2) and l-cysteine (l-Cys). Methods Molybdenum-based synthetic nano-enzymes (Synz) were fabricated by the flash freeze–heating method. Field emission scanning electron microscopy, energy-dispersive X-ray spectrometry, X-ray diffraction analysis, X-ray photoelectron spectroscopy (HP-XPS) and Fourier transform infrared spectroscopy were used for the physicochemical characterization of the developed Synz. Ultraviolet–visible (UV–Vis) absorption spectra were used to detect both H2O2 and l-Cys. Digital photographs were taken to visualize the colour changes in Synz-coated paper incubated with both H2O2 and l-Cys. Results Synz was used as a colorimetric biosensor for the detection of both H2O2 and l-Cys. Furthermore, co-incubation with lipopolysaccharide and Synz reduced the levels of both H2O2 and reactive oxygen species in J77A4 macrophage cells. Additionally, the incubation of H2O2 on Synz-coated cellulose filter paper led to a substantial change in the paper’s colour from blue to white with a low H2O2 detection limit of 10 μM and, on the contrary, retained the blue colour with the addition of an l-Cys + H2O2 solution with l-Cys concentration detection limit of 70 μM. Conclusion Collectively, our results show Synz to be a promising catalase-mimicking biomaterial that can alleviate H2O2 and be used to develop a low-cost colorimetric paper biosensor for prognostic or theranostic applications.
Rajendrakumar, Santhosh Kalash,Chang, Ning-Chu,Mohapatra, Adityanarayan,Uthaman, Saji,Lee, Byeong-Il,Tsai, Wei-bor,Park, In-Kyu MDPI 2018 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.19 No.4
<P>To prolong blood circulation and avoid the triggering of immune responses, nanoparticles in the bloodstream require conjugation with polyethylene glycol (PEG). However, PEGylation hinders the interaction between the nanoparticles and the tumor cells and therefore limits the applications of PEGylated nanoparticles for therapeutic drug delivery. To overcome this limitation, zwitterionic materials can be used to enhance the systemic blood circulation and tumor-specific delivery of hydrophobic agents such as IR-780 iodide dye for photothermal therapy. Herein, we developed micellar nanoparticles using the amphiphilic homopolymer poly(12-(methacryloyloxy)dodecyl phosphorylcholine) (PCB-lipid) synthesized via reversible addition–fragmentation chain transfer (RAFT) polymerization. The PCB-lipid can self-assemble into micelles and encapsulate IR-780 dye (PCB-lipid–IR-780). Our results demonstrated that PCB-lipid–IR-780 nanoparticle (NP) exhibited low cytotoxicity and remarkable photothermal cytotoxicity to cervical cancer cells (TC-1) upon near-infrared (NIR) laser irradiation. The biodistribution of PCB-lipid–IR-780 showed higher accumulation of PCB-lipid–IR-780 than that of free IR-780 in the TC-1 tumor. Furthermore, following NIR laser irradiation of the tumor region, the PCB-lipid–IR-780 accumulated in the tumor facilitated enhanced tumor ablation and subsequent tumor regression in the TC-1 xenograft model. Hence, these zwitterionic polymer-lipid hybrid micellar nanoparticles show great potential for cancer theranostics and might be beneficial for clinical applications.</P>
Rajendrakumar, Santhosh Kalash,Revuri, Vishnu,Samidurai, Manikandan,Mohapatra, Adityanarayan,Lee, Jae Hyuk,Ganesan, Palanivel,Jo, Jihoon,Lee, Yong-Kyu,Park, In-Kyu American Chemical Society 2018 Nano letters Vol.18 No.10
<P>Oxidative stress during sepsis pathogenesis remains the most-important factor creating imbalance and dysregulation in immune-cell function, usually observed following initial infection. Hydrogen peroxide (H<SUB>2</SUB>O<SUB>2</SUB>), a potentially toxic reactive oxygen species (ROS), is excessively produced by pro-inflammatory immune cells during the initial phases of sepsis and plays a dominant role in regulating the pathways associated with systemic inflammatory immune activation. In the present study, we constructed a peroxide scavenger mannosylated polymeric albumin manganese dioxide (mSPAM) nanoassembly to catalyze the decomposition of H<SUB>2</SUB>O<SUB>2</SUB> responsible for the hyper-activation of pro-inflammatory immune cells. In a detailed manner, we investigated the role of mSPAM nanoassembly in modulating the expression and secretion of pro-inflammatory markers elevated in bacterial lipopolysaccharide (LPS)-mediated endotoxemia during sepsis. Through a facile one-step solution-phase approach, hydrophilic bovine serum albumin reduced manganese dioxide (BM) nanoparticles were synthesized and subsequently self-assembled with cationic mannosylated disulfide cross-linked polyethylenimine (mSP) to formulate mSPAM nanoassembly. In particular, we observed that the highly stable mSPAM nanoassembly suppressed HIF1α expression by scavenging H<SUB>2</SUB>O<SUB>2</SUB> in LPS-induced macrophage cells. Initial investigation revealed that a significant reduction of free radicals by the treatment of mSPAM nanoassembly has reduced the infiltration of neutrophils and other leukocytes in a local endotoxemia animal model. Furthermore, therapeutic studies in a systemic endotoxemia model demonstrated that mSPAM treatment reduced TNF-α and IL-6 inflammatory cytokines in serum, in turn circumventing organ damage done by the inflammatory macrophages. Interestingly, we also observed that the reduction of these inflammatory cytokines by mSPAM nanoassembly further prevented IBA-1 immuno-positive microglial cell activation in the brain and consequently improved the cognitive function of the animals. Altogether, the administration of mSPAM nanoassembly scavenged H<SUB>2</SUB>O<SUB>2</SUB> and suppressed HIF1α expression in LPS-stimulated macrophages and thereby inhibited the progression of local and systemic inflammation as well as neuroinflammation in an LPS-induced endotoxemia model. This mSPAM nanoassembly system could serve as a potent anti-inflammatory agent, and we further anticipate its successful application in treating various inflammation-related diseases.</P> [FIG OMISSION]</BR>