Targeting specific response tumor microenvironment nano-photosensitizer, and preparation method and application thereof
A tumor microenvironment, specific technology, applied in the direction of antitumor drugs, pharmaceutical formulations, preparations for in vivo testing, etc. It is suitable for promotion and large-scale production, improving the hypoxic environment of tumors, and relieving the effect of the slightly acidic environment of tumors
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[0054] The preparation of MnO@oleylamine can refer to the prior art, and its steps can be preferably referred to as follows:
[0055] Divalent manganese salt (preferably Mn(OAc) 2 ), oleylamine (Oleyamine, OA), and a solvent (preferably diphenyl ether) are mixed and dissolved, and then preferably under nitrogen protection conditions, a heating reaction is carried out; in the reaction, oleylamine is used as a reducing agent ligand and a reducing agent, Mn(OAc) 2 The reaction is decomposed into MnO@oleylamine;
[0056] The heating reaction can preferably be carried out as follows: under the condition of nitrogen protection, the mixture of divalent manganese salt, oleylamine and solvent is heated with a 120°C electric heating mantle for 0.5h to remove moisture; then the temperature is raised to 10°C / min. 280°C, stop heating after stirring for 1 hour, and cool the solution to room temperature;
[0057] The product obtained from the heating reaction needs to be further post-trea...
Embodiment 1
[0092] Embodiment 1 method flow can refer to figure 1 , the specific operation steps can be referred to as follows:
[0093] (a) Preparation of MnO@OA nanoparticles
[0094] 2g Mn(oac) 2 , 25ml of diphenyl ether, and 25ml of oleylamine (Oleyamine, OA) were mixed and dissolved in a 100ml three-necked flask, and the mixture was reacted under the protection of nitrogen; first, the excess water in the reaction was removed by heating at 120°C for 0.5h with an electric heating mantle, and then The temperature was raised to 280°C at a rate of 10°C / min, and the reaction was stirred for 1 hour, then the heating was stopped, and the solution was cooled to room temperature.
[0095] Add 100mL ethanol to the solution to precipitate the generated MnO nanoparticles, and then centrifuge at 8000rpm for 10min to obtain MnO@OA particles with a size of about 20nm, which are dispersed in chloroform for use at a concentration of about 20mg / mL.
[0096] For the morphology and characterization of...
Embodiment 2
[0122] (a) Preparation of MnO@OA nanoparticles
[0123] 5g Mn(oac) 2 , 50ml of diphenyl ether, and 40ml of oleylamine (Oleyamine, OA) were mixed and dissolved in a 100ml three-necked flask, and the mixture was reacted under the protection of nitrogen; first, the excess water in the reaction was removed by heating with an electric heating mantle at 120°C for 0.5h, and then The temperature was raised to 280°C at a rate of 10°C / min, and the reaction was stirred for 1 hour, then the heating was stopped, and the solution was cooled to room temperature.
[0124] (b) PSMA-PEG 2k -NH 2 preparation
[0125] Will NH 2 -PEG 2k -NH-Boc 150mg and PMSA 200mg were dissolved in 5ml DMSO solution, and the solution was placed in a round bottom flask; then 25mg DMAP was added to the flask as a catalyst, heated to 60°C, and reacted overnight.
[0126] After the reaction, put the reaction product into a dialysis bag with a molecular weight of 3.5 kDa, dialyze with ultrapure water for three d...
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