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Construction and application of near-infrared light activated macrophage-nano prodrug targeted drug delivery system

A technology of macrophages and near-infrared light, which is applied in nano-medicine, nano-technology, nano-optics, etc., can solve the problem of synchronous release of photosensitive molecules and cytotoxic chemotherapy drugs, synchronous delivery of photosensitive active molecules and synchronous delivery of macrophages. Chemotherapy prodrugs, immunogenic cell death and other problems, to achieve the effect of efficient drug delivery, high drug loading, and efficient treatment

Active Publication Date: 2021-10-01
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005]Although there have been many research reports on macrophage-based drug delivery vehicles, there is no synchronous delivery of macrophage-based drug delivery vehicles Reports on photosensitizing active molecules and chemotherapeutic prodrugs, and in the controlled drug release mechanism based on macrophage carriers, there is no report on the simultaneous release of photosensitizing molecules and cytotoxic chemotherapeutics using near-infrared light
In addition, there is no report on a drug delivery system based on macrophages that irradiates the tumor in situ with light, thereby activating chemotherapy and photodynamic effects, inducing immunogenic cell death in the tumor, and thus inhibiting distant metastases

Method used

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  • Construction and application of near-infrared light activated macrophage-nano prodrug targeted drug delivery system
  • Construction and application of near-infrared light activated macrophage-nano prodrug targeted drug delivery system
  • Construction and application of near-infrared light activated macrophage-nano prodrug targeted drug delivery system

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0062] Example 1: Preparation of light-activated prodrug nanocarriers:

[0063] The DOPA-wrapped prodrug nanocarrier core was prepared by reverse microemulsion method. The specific operation is as follows: a cyclohexane solution containing 0.3M triton and 1.5M n-hexanol is prepared as the oil phase of the microemulsion method. Slowly add 200 μL carboxylated oxaliplatin sodium salt solution (8.83 mg / mL) into 5 mL oil phase as the drug phase, and simultaneously add 200 μL Zn 2+ The aqueous solution (25mg / mL) was slowly added to another same 5mL oil phase as the ionic phase, and each was stirred at room temperature for 5min to form a transparent W / O microemulsion. 30 μL of DOPA chloroform solution (138 mM) was added into the ionic phase, and after stirring for 5 min, the drug phase was slowly added dropwise into the ionic phase while stirring. After the mixed solution was continuously stirred at room temperature for 45 min, 10 mL of absolute ethanol was added, and the product...

example 2

[0066] Example 2: Acquisition of BMDM:

[0067] Firstly, L929 cell conditioned medium (L929-CM) is prepared, and the specific preparation operation is as follows: after L929 cells are subcultured, when the density reaches 50%-80%, continue to culture for 5-7 days. The supernatant was collected, centrifuged at 1000rpm for 6min, filtered through a 0.22μm filter membrane, dispensed into 5mL EP tubes, and stored in a -20°C refrigerator for later use.

[0068] The preparation of BMDM is as follows: C57BL / 6 mice aged 8-12 weeks were sacrificed by cervical dislocation and immediately soaked in 75% ethanol solution for 5 minutes, then transferred to the ultra-clean bench, and the skin and muscles were quickly separated by reverse dissection, free and clean and intact femur and tibia. After washing with sterile pre-cooled PBS, the bone marrow cavity was carefully exposed with surgical scissors, and a 10 mL syringe with a 1 mL syringe needle was used to absorb serum-free DMEM and ins...

example 3

[0070] Example 3: Cell Carrier Drug Loading Determination:

[0071] The same number of BMDMs (1×10 6 1) were incubated with the same volume of different concentrations of prodrug nanocarriers at 37°C for 2 h, wherein the incubation concentrations of platinum were 500, 400, 300, 150 and 75 μM; the corresponding incubation concentrations of photosensitizers were 200, 160, 120 , 60 and 30 μM. After incubation, the cells were washed 3 times with PBS. The content of photosensitizer zinc phthalocyanine in the cells was measured by fluorescence spectrophotometer. The specific method is: after the incubation, the cells were washed 3 times with PBS, the cells were collected and lysed with cell lysate, the aqueous solution was removed by rotary evaporation at 50°C, and then dissolved by adding chloroform to destroy lipid molecules such as lipid cell membranes, DOPC and cholesterol For the coating of zinc phthalocyanine, free zinc phthalocyanine is released, then chloroform is remov...

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Abstract

According to the invention, a carboxylated platinum prodrug is designed and synthesized, and a coordination nano core is prepared by utilizing the coordination effect of ions and the prodrug. Lipid is wrapped outside the nano-core, and a photosensitizer is dispersed in the nano-core to construct the prodrug nano-carrier. A nano prodrug is loaded by utilizing the phagocytic function of macrophages (BMDM), so that a near-infrared light (NIR) activated macrophage-nano prodrug delivery system is prepared. The system has the characteristics of high drug loading capacity, light-operated activation and retention of self activity and functions, and efficient and synchronous drug delivery of primary tumors and metastatic tumors can be realized after intravenous injection. Meanwhile, after primary tumors are irradiated by NIR, drugs can be triggered to be released quickly, chemotherapy-photodynamic combined therapy is achieved, and the purposes of killing tumor cells and activating an immune system are achieved. Through combination of three modes of chemotherapy, photodynamic and immunization, dual treatment of primary and metastatic tumors is finally realized.

Description

technical field [0001] The invention belongs to the technical field of the combination of biological science and drug carrier, and specifically relates to the construction and application of a near-infrared light-activated macrophage drug delivery system. Background technique [0002] Cancer has become the primary threat to human health in the 21st century. Studies have shown that the primary tumor is not the primary cause of death, and as high as 90% of tumor deaths are related to metastasis. Common human tumors are highly prone to metastasis. Chemotherapy, as the most commonly used treatment for clinical tumor treatment, is severely limited by the low tumor selectivity and toxic side effects of chemotherapeutic drugs. In recent years, the targeted delivery mediated by nano drug delivery system can increase the drug concentration at the target site to a certain extent. However, highly vascularized primary tumors often have tortuous vasculature and high hydrostatic pressu...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K41/00A61K47/46A61K45/06A61P35/00A61P35/04B82Y5/00B82Y20/00B82Y30/00B82Y40/00A61K31/555
CPCA61K41/0057A61K9/5068A61K45/06A61K9/0009A61P35/00A61P35/04B82Y5/00B82Y20/00B82Y30/00B82Y40/00A61K41/0076A61K31/555A61K2300/00
Inventor 黄艳娟赵春顺关梓琳
Owner SUN YAT SEN UNIV
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