Nucleic acid aptamer modified molybdenum disulfide nanosheet photothermal agent with targeted identification

Abstract

The invention discloses a nucleic acid aptamer modified molybdenum disulfide nanosheet photothermal agent with targeted identification. A molybdenum disulfide nanosheet photothermal therapy system having the targeting ability is constructed in the invention, wherein the diameter range of a functionalized molybdenum disulfide nanosheet MoS2-BSA-Apt is 80-120 nm; the size of MoS2 in the functionalized molybdenum disulfide nanosheet is 10 nm; the functionalized molybdenum disulfide nanosheet has excellent photothermal effect under irradiation of infrared light; and the functionalized molybdenum disulfide nanosheet has the capability of specifically identifying tumour cells, can be enriched around the tumour cells, and can be moved into target cells. The nucleic acid aptamer modified molybdenum disulfide nanosheet photothermal agent in the invention is an excellent photothermal therapy material, which has excellent biocompatibility and stability, and is high in photothermal conversion efficiency, simple to synthesize, low in cost and toxicity and high in metabolic rate, has the targeting ability, and can be used for treating tumours precisely and effectively.

Description

technical field

[0001] The invention relates to a nano-sheet photothermal agent with targeted recognition, in particular to a nucleic acid aptamer-modified molybdenum disulfide nano-sheet photothermal agent with targeted recognition. Background technique

[0002] Cancer is a fatal disease that seriously threatens human health and life, and is one of the major public health problems facing the current society. So far, more than 100 kinds of cancers have been discovered one after another, and corresponding treatments will be adopted clinically for the development and progress of different cancers. Clinical treatment of cancer mainly includes chemotherapy, radiotherapy and surgery. Chemotherapy and radiotherapy have the problem of non-selective damage to normal tissues of the body. While eliminating tumor cells, they will also bring relatively large side effects to patients. For some tumors that are close to important organs of the human body, surgical resection of the tumor ...

Examples

Embodiment 1

[0068] Example 1: MOS2-BSA synthesis condition optimization research and photothermal performance research

[0069] (1) Dissolve 0.25g sodium molybdate in 25mL ultrapure water, and after ultrasonic oscillation for 5 minutes, adjust the pH of the solution to 6.5 with 0.1mol L-1HCl; dissolve 0.5g cysteine ​​in ultrapure water and dilute to 50mL , to obtain a cysteine ​​solution. Slowly add cysteine ​​solution and a certain amount of stripping agent glucose into sodium molybdate solution in sequence, and after ultrasonic oscillation, transfer the mixed solution to a hydrothermal reaction kettle; hydrothermal reaction at 200°C for a certain period of time, one-step hydrothermal synthesis The molybdenum disulfide was naturally cooled to room temperature, centrifuged at 12,000 rpm for 30 minutes, and the collected supernatant was molybdenum disulfide nanosheets; freeze-dried for 12 hours to obtain solid molybdenum disulfide nanosheets. When synthesizing molybdenum disulfide nanoshe...

Embodiment 2

[0075] Example 2: Research on MoS2-BSA coupled nucleic acid aptamer and photothermal effect

[0076] (1) Take EDC (500 μl, 500 mM) and NHS (500 μl, 100 mM) to activate the free carboxyl groups on the surface of MoS2-BSA obtained in Example 1, and react 1 mL of MoS2-BSA with EDC and NHS at room temperature for half an hour, over Filtrate and centrifuge, wash with deionized water to obtain activated MoS2-BSA sheets; denature the nucleic acid aptamer (Apt, 5'-NH2-AGGAGCACGACTCTGACGTAGGATCGAGACGAGGTACGTAT-3') at 85°C for 10 minutes, then renature in ice bath for 10 minutes; the activated MoS2- The BSA sheet was reacted with the nucleic acid aptamer in an ice bath for 5 h, followed by ultrafiltration and centrifugation at 4000 rpm until no aptamer was detected in the ultrafiltrate, and finally aptamer-modified MoS2-BSA-Apt nanosheets were obtained.

[0077] The product obtained in this example is characterized, wherein the absorption spectra of MoS modified BSA and Apt are as follo...

Embodiment 3

[0080] Example 3: Characterization of functionalized molybdenum disulfide nanosheets

[0081] To the MoS that makes in embodiment 1,2, MoS2-BSA, MoS2-BSA-Apt is carried out by transmission electron microscope (TEM), high-resolution transmission electron microscope (HRTEM), X-ray diffraction spectrum (XRD) and zeta potential characterization.

[0082] Morphological characterization of the MoS2, MoS2-BSA, MoS2-BSA-Apt nanosheets prepared in 1 and 2, the TEM results are as follows Image 6 , 7, 8. Image 6 It can be seen that the size of MoS2 nanosheets is about 10nm to 50nm, and the lattice spacing is about 0.62nm, which is consistent with the literature (Liu Q, PuZH, Abdullah M. Asiri, etal. One-step solvothermal synthesis of MoS2 / TiO2 nanocomposites with enhanced photocatalytic The (002) crystal plane of hexagonal MoS2 reported by H2 production [J]. NanopartRes, 2013, 15: 2057). Figure 7 There are some circular MoS2 black spots on the BSA surface of MoS2-BSA nanosheets wit...

technical field

[0001] The invention relates to a nano-sheet photothermal agent with targeted recognition, in particular to a nucleic acid aptamer-modified molybdenum disulfide nano-sheet photothermal agent with targeted recognition. Background technique

[0002] Cancer is a fatal disease that seriously threatens human health and life, and is one of the major public health problems facing the current society. So far, more than 100 kinds of cancers have been discovered one after another, and corresponding treatments will be adopted clinically for the development and progress of different cancers. Clinical treatment of cancer mainly includes chemotherapy, radiotherapy and surgery. Chemotherapy and radiotherapy have the problem of non-selective damage to normal tissues of the body. While eliminating tumor cells, they will also bring relatively large side effects to patients. For some tumors that are close to important organs of the human body, surgical resection of the tumor ...

Examples

Embodiment 1

[0068] Example 1: MOS2-BSA synthesis condition optimization research and photothermal performance research

[0069] (1) Dissolve 0.25g sodium molybdate in 25mL ultrapure water, and after ultrasonic oscillation for 5 minutes, adjust the pH of the solution to 6.5 with 0.1mol L-1HCl; dissolve 0.5g cysteine ​​in ultrapure water and dilute to 50mL , to obtain a cysteine ​​solution. Slowly add cysteine ​​solution and a certain amount of stripping agent glucose into sodium molybdate solution in sequence, and after ultrasonic oscillation, transfer the mixed solution to a hydrothermal reaction kettle; hydrothermal reaction at 200°C for a certain period of time, one-step hydrothermal synthesis The molybdenum disulfide was naturally cooled to room temperature, centrifuged at 12,000 rpm for 30 minutes, and the collected supernatant was molybdenum disulfide nanosheets; freeze-dried for 12 hours to obtain solid molybdenum disulfide nanosheets. When synthesizing molybdenum disulfide nanoshe...

Embodiment 2

[0075] Example 2: Research on MoS2-BSA coupled nucleic acid aptamer and photothermal effect

[0076] (1) Take EDC (500 μl, 500 mM) and NHS (500 μl, 100 mM) to activate the free carboxyl groups on the surface of MoS2-BSA obtained in Example 1, and react 1 mL of MoS2-BSA with EDC and NHS at room temperature for half an hour, over Filtrate and centrifuge, wash with deionized water to obtain activated MoS2-BSA sheets; denature the nucleic acid aptamer (Apt, 5'-NH2-AGGAGCACGACTCTGACGTAGGATCGAGACGAGGTACGTAT-3') at 85°C for 10 minutes, then renature in ice bath for 10 minutes; the activated MoS2- The BSA sheet was reacted with the nucleic acid aptamer in an ice bath for 5 h, followed by ultrafiltration and centrifugation at 4000 rpm until no aptamer was detected in the ultrafiltrate, and finally aptamer-modified MoS2-BSA-Apt nanosheets were obtained.

[0077] The product obtained in this example is characterized, wherein the absorption spectra of MoS modified BSA and Apt are as follo...

Embodiment 3

[0080] Example 3: Characterization of functionalized molybdenum disulfide nanosheets

[0081] To the MoS that makes in embodiment 1,2, MoS2-BSA, MoS2-BSA-Apt is carried out by transmission electron microscope (TEM), high-resolution transmission electron microscope (HRTEM), X-ray diffraction spectrum (XRD) and zeta potential characterization.

[0082] Morphological characterization of the MoS2, MoS2-BSA, MoS2-BSA-Apt nanosheets prepared in 1 and 2, the TEM results are as follows Image 6 , 7, 8. Image 6 It can be seen that the size of MoS2 nanosheets is about 10nm to 50nm, and the lattice spacing is about 0.62nm, which is consistent with the literature (Liu Q, PuZH, Abdullah M. Asiri, etal. One-step solvothermal synthesis of MoS2 / TiO2 nanocomposites with enhanced photocatalytic The (002) crystal plane of hexagonal MoS2 reported by H2 production [J]. NanopartRes, 2013, 15: 2057). Figure 7 There are some circular MoS2 black spots on the BSA surface of MoS2-BSA nanosheets wit...

Images