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Nano material for light-enhanced chemotherapy and integrated tumor diagnosis and treatment as well as preparation method and application of nano material

A nanomaterial and tumor technology, which is applied in the field of nanobiomedicine technology and tumor diagnosis and treatment, can solve the problems of difficult tumor enrichment, unexplained trigger mechanism, difficulty in metabolism and excretion, etc., achieve long cycle time, realize precise release, biophase good capacitive effect

Active Publication Date: 2022-07-05
SOUTH CHINA UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

But its weak point is: (1) the Cu metal element contained in the inorganic nanoparticles used, especially the hollow copper sulfide nanoparticles, as a trace element in the body, excessive copper has biological toxicity, and it is difficult to metabolize and excrete in the body; (2) Molecularly targeted prodrug PDC refers to the conjugate obtained by coupling RGD polypeptide and chemotherapeutic drugs through small molecule linking bridge arms
RGD is expressed differently in tumor tissues, and it is known that only a few highly expressed ones may have the described affinity; (3) the particle size of the nanostructure is about 200nm, and it is difficult to enrich the tumor; (4) the NIR laser irradiation Triggered drug release, trigger mechanism unspecified

Method used

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  • Nano material for light-enhanced chemotherapy and integrated tumor diagnosis and treatment as well as preparation method and application of nano material
  • Nano material for light-enhanced chemotherapy and integrated tumor diagnosis and treatment as well as preparation method and application of nano material
  • Nano material for light-enhanced chemotherapy and integrated tumor diagnosis and treatment as well as preparation method and application of nano material

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Example 1 Preparation of cisplatin prodrug Pt(IV)-2COOH(DSP):

[0047]

[0048] The synthetic route is as follows:

[0049]

[0050] a) Disperse yellow powder cisplatin (1 g) in water (50 mL) and stir at 50°C. Then add H 2 O 2 (35 mL, 30%) and stirred at 75°C for 5 hours. During this process, cisplatin dissolves into a colorless and transparent solution. After returning to room temperature, the reaction solution was recrystallized at -20°C for 12 hours. The obtained yellow Pt(IV)-2OH solid was washed with cold ether and dried in an oven in 60% yield. The product was collected for the next reaction.

[0051] b) Pt(IV)-2OH (0.35 g) and succinic anhydride (1 g) were added to DMF (3 mL) and stirred at 70° C. for 24 h. Then cold diethyl ether was added to the mixed solution and recrystallized at -20°C to obtain a white solid Pt(IV)-2COOH with a yield of 45%.

[0052] The cisplatin prodrug DSP synthesized in this example 1 The H NMR spectrum is shown in Figure ...

Embodiment 2B

[0054] Example 2 Preparation of BSA and cisplatin prodrug DSP conjugate (BSA-DSP):

[0055] a) DSP (60 mg, 0.11 mol), EDC·HCl (52.72 mg, 0.28 mol), sulfo-NHS (477.69 mg, 2.2 mol) were mixed in water (10 mL, pH 7.0) at room temperature for 30 minutes.

[0056] b) BSA (1.86 g, 0.028 mol) was then dissolved in 100 mL of PBS buffer and added to the above solution, and the resulting mixture was stirred at 30° C. for 2.5 hours. The mixture was washed with PBS buffer and ultrafiltered 3 times through an ultrafiltration device (MWCO=10 kDa) at 4000 rpm for 20 minutes to remove unbound DSP and unreacted compounds, resulting in BSA-DSP. BSA-DSP solution in PBS buffer (DSP 1.11 mg·mL -1 , Pt(IV)503.90μg·mL -1 , BSA 183.12mg·mL -1 ) was ultrafiltered to 6mL for later use.

Embodiment 3

[0057] Example 3 Preparation of a nanomaterial (BITT@BSA-DSP) for light-enhanced chemotherapy and integrated tumor diagnosis and treatment:

[0058] a) Dissolve 1 mg BITT in ethanol (10 mg mL -1 ) to make a stock solution, and BSA was diluted with PBS buffer (BSA 1 mg mL -1 ). The BITT stock solutions (0.05 mL, 0.10 mL, 0.15 mL, and 0.20 mL) were then diluted to 1 mL with ethanol, and the diluted BITT stock solutions were quickly added to the BSA solution (1 mg mL -1, 10 mL), and used a tip probe sonicator (Qsonica Sonicators Q125, USA) at 25W output for 1 minute on ice to obtain BITT and albumin feeding ratios of 5:100, 10:00, 15:1, respectively. 100 and 20:100 (w / w) BITT@BSA nanoparticle suspensions. BITT@BSA nanoparticles were shown in brightfield and fluorescence imaging, respectively. figure 2 A and figure 2 As shown in B, the BITT photosensitizer encapsulated with BSA albumin has higher fluorescence intensity, but the fluorescence gradually weakens as the ratio of B...

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Abstract

The invention discloses a nano material for light-enhanced chemotherapy and integrated tumor diagnosis and treatment as well as a preparation method and application of the nano material. According to the nano material, albumin coupled with a cis-platinum prodrug and a photosensitizer with aggregation-induced emission properties are self-assembled, and protein cage-shaped multifunctional nano particles loaded with molecular aggregates are successfully constructed. The nano material has the following advantages: 1) tumor in-situ diagnosis is realized through near infrared fluorescence emission; 2) the particle size can be regulated and controlled, and enrichment in tumors is realized by enhancing permeation and retention effects; 3) the cage structure of the protein can realize photoresponse depolymerization and release of the photosensitizer; and 4) the coupled cis-platinum prodrug is promoted to be activated by highly expressed reducing substances in tumor cells through optical excitation, so that targeted release of chemotherapeutic drugs in tumors is realized. The invention also discloses an anti-tumor application of the nano material, and the nano material can realize tumor fluorescence diagnosis and light-enhanced chemotherapy, reduces the chemotherapeutic drug dosage of tumors, and is expected to improve the chemotherapeutic effect of drug-resistant tumors.

Description

technical field [0001] The invention belongs to the fields of nanometer biomedical technology and tumor diagnosis and treatment technology, and particularly relates to a nanomaterial with light-enhanced chemotherapy and integrated tumor diagnosis and treatment, and a preparation method and application thereof. Background technique [0002] Bladder cancer is one of the most common tumors worldwide, with approximately 573,000 new cases and 213,000 deaths each year, posing a great social burden. Surgery combined with chemotherapy, as a widely used treatment for bladder cancer, still faces extremely high recurrence and metastasis rates, mainly due to the insensitivity of residual small lesions and invasive micrometastases to chemotherapeutic drugs. Although platinum-based neoadjuvant chemotherapy has been recommended by many diagnosis and treatment guidelines for the comprehensive treatment of muscle-invasive bladder cancer, the dose-dependent side effects significantly restrict...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K41/00A61K33/243A61K47/64A61K47/69A61K49/00A61P35/00B82Y5/00B82Y40/00B82Y20/00
CPCA61K41/0057A61K41/0052A61K41/0042A61K33/243A61K47/64A61K47/6929A61K49/0021A61K49/0056A61K49/0093A61P35/00B82Y5/00B82Y40/00B82Y20/00A61K2300/00
Inventor 唐本忠丁可珂王志明王俪蓉
Owner SOUTH CHINA UNIV OF TECH
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