Self‐production of oxygen system CaO₂/MnO₂@PDA‐MB for the photodynamic therapy research and switch‐control tumor cell imaging

Abstract

Photodynamic therapy (PDT) holds promise in biochemical study and tumor treatment. A novel multifunctional nanosystem CaO /MnO @polydopamine (PDA)-methylene blue (MB) nanosheet (CMP-MB) was designed. CaO nanoparticles were encapsulated by MnO nanosheet, and then PDA was coated on the surface of CaO /MnO nanosheets, which could adsorb photosensitizer MB through hydrophobic interaction or π-π stacking. In this nanosystem, CaO /MnO had the ability of self-production of oxygen, which solved the problem of tumor hypoxia largely. Moreover, it is worth mentioning that the fluorescence of MB was suppressed by MnO , while its emission was triggered in the simulated tumor microenvironment. Therefore, CMP-MB nanosheet could be used to switch-control cell imaging potentially. 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide testing and Live/Dead assay confirmed CMP-MB nanosheet had fewer side effects without illumination while it destroyed Hela cell with the illumination of light. Vitro cell experiment demonstrated CMP-MB nanosheet could achieve tumor microenvironment responsive imaging and inhibit tumor cell growth under illumination effectively. Therefore, the system has great potential for PDT application and switch-control tumor cell imaging. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2544-2552, 2018.

<p>Manganese dioxide nanosheets: from preparation to biomedical applications</p>

“…Once exposed to a tumor microenvironment, the MnO 2 NSs could decompose into Mn 2+ , which triggered the emission of MB fluorescence. Hence, switch-controlled tumor cell imaging was achieved 84. Xia et al found that the MnO 2 NS mediated quenching effect can be reversed via the reduction of MnO 2 into Mn 2+ by ascorbic acid (AA), resulting in MnO 2 NS destruction.…”

Metal peroxides for cancer treatment

“…To date, several preparation methods of MO 2 are developed, including hydrolyzation-precipitation method [ 22 , 23 ], underwater Leidenfrost dynamic chemistry method [ 24 ], reversed-phase microemulsion method [ 25 ], gas diffusion method [ 26 ], and sonochemical method [ 27 ]. Due to the instability of MO 2 , some surface modification is necessary to achieve better applications in biomedical fields, frequently used surface modifiers are polyethylene glycol (PEG), polyvinyl pyrrolidone (PVP), CO-520, and hyaluronic acid (HA) [ 23 , 25 , 28 , 29 ]. Proper surface modification not only increases the stability of MO 2 , but also improves the dispersion of nanoparticles (NPs), even be possible to target the tumor.…”

“… MO 2 Preparation Morphology and size Surface modifier Applications Ref. CaO 2 Hydrolyzation-precipitation method Particle, <5 nm SH Calcium-overload/Oxidation therapy [ 20 ] CaO 2 Hydrolyzation-precipitation method Particle, 15 ± 10 nm PEG-200 PDT [ 22 ] CaO 2 Hydrolyzation-precipitation method Spherical structure, 5–15 nm PEG-200 PDT [ 23 ] CaO 2 Hydrolyzation-precipitation method Particle PVP PDT [ 28 ] CaO 2 Hydrolyzation-precipitation method Particle, 107 ± 11 nm HA CDT [ 29 ] CaO 2 Hydrolyzation-precipitation method Clusters, 300 ± 20 nm PEG-200 PDT [ 30 ] CaO 2 Hydrolyzation-precipitation method Spherical structure, 116.0 ± 7.6 nm PEG-200 PDT [ 31 ] CaO 2 Hydrolyzation-precipitation method Particle, ＜200 nm PEG-200 Chemotherapy/CDT ...…”

“…For example, CaO 2 reacts with H 2 O to generate H 2 O 2 (Eq (3) ) which provide a raw material for manganese dioxide (MnO 2 ) for the generation of O 2 in a mild acid environment, Eq (4) [ 60 ]. By this way, Shi and his colleagues prepared a CaO 2 /MnO 2 @PDA-MB, system through MnO 2 nanosheet coated on the surface of CaO 2 , in acidic TME, polydopamin (PDA) dissolution enables Mn 2+ to fully react with H 2 O 2 produced by CaO 2 and generate O 2 , further promoting the PDT effects of MB that the singlet oxygen quantum yield reached 0.18 and realized switch-control fluorescence imaging [ 28 ]. CaO 2 +2H 2 O → H 2 O 2 + Ca(OH) 2 MnO 2 + H 2 O 2 + 2H + → Mn 2+ +2H 2 O + O 2 …”

Inhibition of photodynamic therapy induced‑immunosuppression with aminolevulinic acid leads to enhanced outcomes of tumors and pre‑cancerous lesions (Review)

“…Reversing a hypoxic state in a tumor was also shown to impede the MDSC-regulated pathway ( 55 , 56 ). Hypoxia is produced by consuming oxygen after making ATP (adenosine triphosphate), thus, reversing it can be achieved by interfering with oxidative phosphorylation ( 57 , 58 ). This study used platelet membranes as nano-carriers called PM-IR780-Met, which included encapsulated metformin whose role was to decrease oxygen consumption by inhibiting the mitochondrial respiratory chain.…”