Platinum drugphotosensitizer-loaded protein nanoparticles and preparation method and application thereof

Abstract

The invention relates to platinum drugphotosensitizer-loaded protein nanoparticles and a preparation method and application thereof. The platinum drugphotosensitizer-loaded protein nanoparticles comprise platinum drugphotosensitizer complexes and proteins wrapping the platinum drugphotosensitizer complexes. Chemical therapy and photodynamic therapy are combined through an albumin nano-drug delivery system so that a synergistic anti-cancer effect is achieved, and the toxicity-reducing and efficacy-improving treatment effect is achieved. The nanoparticles prepared by the method are small in particle size, uniform in dispersion and round in shape; good chemical stability and illumination stability are realized; under the irradiation of near-infrared light, the nanoparticles have relatively high active oxygen generation capability; in addition, in cell experiments and animal experiments, it is verified that the nanoparticle has strong cytotoxicity and good in-vivo tumor targeting to tumorcells, plays a synergistic effect, reduces toxic and side effects, realizes combined treatment of tumors by chemotherapy and photodynamic therapy, and inhibits tumor metastasis.

Description

Technical field

[0001] The invention relates to the preparation of albumin nanoparticles with dual therapeutic effects containing platinum drugs and photosensitizers, which are used as a new dosage form of antitumor drugs to realize combined treatment of tumors and inhibit tumor metastasis. Background technique

[0002] Malignant tumors are serious diseases that threaten human health. Clinical treatment needs to treat and suppress metastasis equally.

[0003] At present, there are many kinds of materials studied as nano-drug delivery systems. The preparation of nano-materials with biological macromolecular proteins as carriers has the advantages of good biocompatibility, safety and non-toxicity. As a carrier material for drugs, it can selectively target drugs The diseased part can effectively reduce its toxic and side effects on normal tissues, so it has an important position and research value in the pharmaceutical research of nano-medicine carriers and anti-tumor.

[0004] Albumin...

Examples

Embodiment 1

[0045] Weigh 720 mg of cisplatin (Pt(NH 3 ) 2 Cl 2 , 2.4 mmol·L -1 ) And 800 mg silver nitrate (AgNO 3 , 4.7 mmol·L -1 ), dissolved in 6.0 mL of distilled water, stirred in a water bath (60℃) protected from light for 3 hours, and then stirred at room temperature for 20 hours; after the reaction is over, take out the reaction solution (the reaction solution is clear without turbidity) 14000 r ·min -1 Centrifuge for 15 min to remove the AgCl precipitate generated. The supernatant was filtered with a 0.22 μm filter to obtain diamine platinum nitric acid dihydrate ([Pt(NH 3 ) 2 (H 2 O) 2 ](NO 3 ) 2 ) Solution; determine its concentration by inductively coupled plasma emission spectrometer (ICP-OES) and add water to adjust the final concentration to 320 mmol·L -1 , Is the concentration of the stock solution, diluted with water to 32 mmol·L when preparing nanoparticles -1 .

[0046] Use 10 mg·mL -1 10 mL of HAS aqueous solution, add a concentration of 32 mmol·L -1 1 mL of diamine platinum...

Embodiment 2

[0090] When preparing protein nanoparticles in Example 1, the pH was adjusted to 5.0 and 6.0 respectively (in Example 1, the pH was 5.5), and the other steps were the same as in Example 1. The TEM size could be 4.5~5.3 nm (due to weight Atomic action only reflects the size of the area where the platinum atom in the core of the nanoparticle is located, the same below).

Embodiment 3

[0092] In the preparation process of the protein nanoparticles in Example 1, the molar ratio of platinum to Ce6 was adjusted to 1:1, 8:1 (in Example 1, the molar ratio of Pt:Ce6 was 4:1), and other conditions and implementation In the same case as in Example 1, Pt / Ce6 protein nanoparticles with good stability can be prepared, and the TEM size is between 4.2 and 4.9 nm.

[0093] During the preparation process of protein nanoparticles in Example 1, the molar ratio of platinum to Ce6 was adjusted to 1:2 (in Example 1, the molar ratio of Pt:Ce6 was 4:1), and other conditions were the same as in Example 1. The latter solution was turbid, and Pt / Ce6 protein nanoparticles with good stability could not be prepared.

Technical field

[0001] The invention relates to the preparation of albumin nanoparticles with dual therapeutic effects containing platinum drugs and photosensitizers, which are used as a new dosage form of antitumor drugs to realize combined treatment of tumors and inhibit tumor metastasis. Background technique

[0002] Malignant tumors are serious diseases that threaten human health. Clinical treatment needs to treat and suppress metastasis equally.

[0003] At present, there are many kinds of materials studied as nano-drug delivery systems. The preparation of nano-materials with biological macromolecular proteins as carriers has the advantages of good biocompatibility, safety and non-toxicity. As a carrier material for drugs, it can selectively target drugs The diseased part can effectively reduce its toxic and side effects on normal tissues, so it has an important position and research value in the pharmaceutical research of nano-medicine carriers and anti-tumor.

[0004] Albumin...

Examples

Embodiment 1

[0045] Weigh 720 mg of cisplatin (Pt(NH 3 ) 2 Cl 2 , 2.4 mmol·L -1 ) And 800 mg silver nitrate (AgNO 3 , 4.7 mmol·L -1 ), dissolved in 6.0 mL of distilled water, stirred in a water bath (60℃) protected from light for 3 hours, and then stirred at room temperature for 20 hours; after the reaction is over, take out the reaction solution (the reaction solution is clear without turbidity) 14000 r ·min -1 Centrifuge for 15 min to remove the AgCl precipitate generated. The supernatant was filtered with a 0.22 μm filter to obtain diamine platinum nitric acid dihydrate ([Pt(NH 3 ) 2 (H 2 O) 2 ](NO 3 ) 2 ) Solution; determine its concentration by inductively coupled plasma emission spectrometer (ICP-OES) and add water to adjust the final concentration to 320 mmol·L -1 , Is the concentration of the stock solution, diluted with water to 32 mmol·L when preparing nanoparticles -1 .

[0046] Use 10 mg·mL -1 10 mL of HAS aqueous solution, add a concentration of 32 mmol·L -1 1 mL of diamine platinum...

Embodiment 2

[0090] When preparing protein nanoparticles in Example 1, the pH was adjusted to 5.0 and 6.0 respectively (in Example 1, the pH was 5.5), and the other steps were the same as in Example 1. The TEM size could be 4.5~5.3 nm (due to weight Atomic action only reflects the size of the area where the platinum atom in the core of the nanoparticle is located, the same below).

Embodiment 3

[0092] In the preparation process of the protein nanoparticles in Example 1, the molar ratio of platinum to Ce6 was adjusted to 1:1, 8:1 (in Example 1, the molar ratio of Pt:Ce6 was 4:1), and other conditions and implementation In the same case as in Example 1, Pt / Ce6 protein nanoparticles with good stability can be prepared, and the TEM size is between 4.2 and 4.9 nm.

[0093] During the preparation process of protein nanoparticles in Example 1, the molar ratio of platinum to Ce6 was adjusted to 1:2 (in Example 1, the molar ratio of Pt:Ce6 was 4:1), and other conditions were the same as in Example 1. The latter solution was turbid, and Pt / Ce6 protein nanoparticles with good stability could not be prepared.

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