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Albumin-stabilized MnO2 nanomaterial as well as preparation method and application

A technology of manganese dioxide and nanomaterials, applied in the field of functional biomimetic nano-drug delivery system, can solve the problems of time-consuming synthesis process, harsh reaction conditions, cumbersome water phase modification steps, etc., and achieve the effect of good biocompatibility

Inactive Publication Date: 2018-06-22
THE THIRD AFFILIATED HOSPITAL INST OF FIELD SURGERY OF PLA ARMY MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Despite its great potential, the vast majority of MnO 2 Nanosheets require time-consuming synthesis processes, harsh reaction conditions, complex ligand exchange, and tedious aqueous phase modification steps, or are synthesized with highly toxic positive polyelectrolytes.

Method used

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  • Albumin-stabilized MnO2 nanomaterial as well as preparation method and application
  • Albumin-stabilized MnO2 nanomaterial as well as preparation method and application
  • Albumin-stabilized MnO2 nanomaterial as well as preparation method and application

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] 1.BSA-MnO 2 Preparation of nanosheets (BMnNSs)

[0032] BMnNSs were synthesized by a biomineralization method using BSA as a stabilizer and reactive scaffold under physiological temperature conditions. At 37°C, 100 mM, 500 μL of MnCl 2 4H 2 O was quickly added to 10 mL of 10 mg / mL BSA solution, and the vortex mixer was shaken vigorously. After 3 minutes, quickly add 250 μL of 1M NaOH solution to adjust the pH to around 12. After adding NaOH, the cloudy solution immediately turned into a transparent light yellow color, and then, as the reaction progressed, the solution gradually turned dark brown. Stand at 37°C for 6 hours to promote crystal growth. Use MWCO=30KDa ultrafiltration tube ultrafiltration 4-5 times to terminate the reaction, 3250 rpm, 15 minutes, to remove excess reactants. Filtered with a 0.22 μm filter membrane, the obtained BMnNSs (BSA-MnO 2 Nanosheets) solution was dispersed in ultrapure water and stored in a 4°C refrigerator for later use.

[003...

Embodiment 2

[0044] Example 2 In vitro cell experiment

[0045] Human glioblastoma cells (U87MG) were provided by Shanghai Academy of Sciences, China. The cells were cultured in DMEM medium containing 10% (v / v) serum, 1% penicillin and streptomycin, and placed in a 5% carbon dioxide incubator at 37°C.

[0046] In vitro cell fluorescence imaging: U87MG cells were incubated with HPPH or BMnHNCs (equivalent to 2 μg / mL HPPH) in the dark for 6 hours, then washed with PBS buffer three times, stained with DAPI, and confocal laser microscopy (CLSM, Olympus FV1200, Japan) to observe and take pictures.

[0047] Cell MRI imaging: U87MG cells were seeded in a 6cm cell culture dish, and when the cells were confluent to about 85%, different concentrations of BMnHNCs were added and incubated for 6 hours. The cells were washed three times with PBS buffer, digested, centrifuged, and collected. The cells were dispersed in 200 μL of 1% low-melting point agarose, and the in vitro cell MRI imaging was perfo...

Embodiment 3

[0054] After the cells were incubated with HPPH or BMnHNCs and irradiated with 630nm laser, the viability of the cells was significantly lower than that of the group without laser irradiation ( image 3 e). After laser irradiation, the viability of BMnHNCs-treated cells was lower than that of HPPH-treated cells. This could be explained by increased cellular internalization efficiency, which was confirmed by cellular CLSM results. Since singlet oxygen is involved in the photodynamic therapy-mediated cell killing effect, from MnO 2 and intracellular H 2 o 2 The O produced by the reaction 2 It can improve the effect of photodynamic therapy. Subsequently, the applicant used the calcein-acetyl hydroxymethyl ester staining method to observe the photodynamic killing effect of HPPH or BMnHNCs on U87MG cells. Such as image 3 As shown in f, U87MG cells treated with only HPPH or only BMnHNCs showed the same green fluorescence as the control cells. However, the cells treated with...

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Abstract

The invention relates to an albumin-stabilized MnO2 nanomaterial as well as a preparation method and an application. The albumin-stabilized MnO2 nanomaterial is a multi-component BMnNSs-HPPH nanocomposite. The nanomaterial is a multi-component nanocomposite (BMnHNCs) with good water dispersity and is formed by loading a photosensitizer HPPH in a BSA-MnO2 nanosheet. By the aid of high reactivity and high specificity of MnO2 for endogenous H2O2 under the acid condition, BMnHNCs can realize NIRF and MRI bimodal imaging response to the tumor microenvironment and tumor microenvironment enhanced photodynamic therapy. The nanocomposite has good biocompability and biodegradability and safe and efficient diagnosis and treatment capacity, will provide a new idea for comprehensively regulating the tumor microenvironment and improving tumor diagnosis and treatment capacity and has greater potentials in the aspects of clinical conversion.

Description

technical field [0001] The invention belongs to the technical field of functional biomimetic nano drug delivery system, and in particular relates to an albumin-stabilized manganese dioxide nano material, its preparation method and application. Background technique [0002] Due to the rapid proliferation of tumor cells, strong glycolytic metabolism and tumor vascular malformation, hypoxia, acidification and high levels of hydrogen peroxide (H 2 o 2 ) are the three most common features of the tumor microenvironment. Hypoxia can not only promote malignant biological phenotypes of tumors (such as tumor angiogenesis, progression, invasion, and metastasis), but also directly cause tumor therapy resistance, especially for treatment modalities that require oxygen participation, such as photodynamic therapy and radiation treatment etc. Therefore, there is an urgent need to develop novel effective strategies to attenuate tumor hypoxia and improve tumor therapeutic response. Oxygen...

Claims

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Application Information

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IPC IPC(8): A61K49/00A61K49/14A61K41/00A61P35/00
CPCA61K49/0002A61K41/0071A61K49/0036A61K49/143
Inventor 刘恒张伟国王舒楠薛巍杜学松童海鹏解添陈晓杨又源
Owner THE THIRD AFFILIATED HOSPITAL INST OF FIELD SURGERY OF PLA ARMY MEDICAL UNIV
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