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Near-infrared light-responsive nanoliposomes and their preparation methods and applications in tumor synergistic therapy

A near-infrared light-responsive, nano-liposome technology, used in liposome delivery, anti-tumor drugs, photodynamic therapy, etc., can solve the problem of poor biocompatibility, pharmacokinetics and efficacy of photothermal agents and photosensitizers Problems such as poor kinetics and sunlight cannot be used and activated to avoid normal cell and tissue damage, good biocompatibility, and significant therapeutic effects

Active Publication Date: 2020-10-13
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Since 46% of the sunlight belongs to the NIR light range, more than half of the sunlight cannot be utilized and activated
However, there are few reports on NIR light harvesting systems
Thirdly, due to the lack of molecular recognition and targeting, photothermal agents and photosensitizers are delivered to the tumor site only based on the enhanced osmotic retention effect during delivery, and are easily distributed in various organs to cause damage to normal cells and tissues. And photosensitizers have poor biocompatibility and are difficult to penetrate cell membranes, resulting in poor pharmacokinetics and pharmacodynamics. How to select biocompatible targeting carriers to efficiently deliver photothermal agents and photosensitizers to tumor cells a big challenge

Method used

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  • Near-infrared light-responsive nanoliposomes and their preparation methods and applications in tumor synergistic therapy
  • Near-infrared light-responsive nanoliposomes and their preparation methods and applications in tumor synergistic therapy
  • Near-infrared light-responsive nanoliposomes and their preparation methods and applications in tumor synergistic therapy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] Example 1: Preparation and characterization of nanoliposomes (UCNPs@BPQDs@Apt-Lip, UBAL) based on upconversion@black phosphorus near-infrared photoresponse:

[0054] (1) Add 30mL of diethylene glycol (DEG) and 300mg of PAA into a 100mL three-neck flask, heat it to 110°C under vacuum, slowly add 100mg of UCNPs nanoparticles dispersed in toluene solution into the flask and under the protection of argon Reaction 1h. The solution was then heated to 240 °C and the reaction was continued for 1.5 h. After cooling to room temperature, ethanol was added to obtain the precipitation of UCNPs-PAA.

[0055] (2) Add 200 mg of block BP to 300 mL of N-methyl-2-pyrrolidone (NMP). Under the protection of argon, use an ultrasonic cell disruptor (ultrasonic frequency: 19-25kHz) to sonicate in an ice / water bath for 8h (2s, with an interval of 0.1s) and then continue to sonicate for 10h (2s, with an interval of 4s) to obtain a brown solution. Centrifuge at 7000rpm for 20min to remove unst...

Embodiment 2

[0064] Example 2: Biocompatibility of UBAL near-infrared light-responsive nanoliposomes in vivo:

[0065] Healthy female Kunming rats (20 g) were injected with 100 μL of 5 mg / kg, 10 mg / kg, and 25 mg / kg of UBAL into the tail vein respectively, and 100 μL of normal saline was used as a negative control. The mice were weighed every 2 days (mouse body weight-time curve). After 28 days, the mice were killed, and 0.8 mL of blood was collected from each mouse for blood routine and blood biochemical analysis, and the main organs of each mouse were collected, fixed in 10% neutral formalin, embedded in paraffin, and sectioned with a thickness of 8 μm , stained with hematoxylin and eosin, and observed with a digital microscope.

[0066] In vivo biocompatibility can further characterize the potential of UBAL in clinical translation. Routine testing of blood was performed after one month of feeding, and biopsies were evaluated by hematoxylin and eosin (H&E) staining. From Figure 9It c...

Embodiment 3

[0067] Example 3: UBAL near-infrared light-responsive nanoliposomes can be used for tumor tissue fluorescence imaging, tumor photokinetic and photothermal therapy:

[0068] (1) 4-week-old female Balb / c nude mice (18-20g) were inoculated with tumors, suspended in DPBS at a density of 1×10 7 Breast cancer cells were injected subcutaneously into the right upper limb of each female Balb / c mouse. On day 5 after tumor cell injection, tumor growth was evident.

[0069] (2) Balb / c nude mice were intravenously injected with UBAL and UBCL (100 μL 5 mg / mL per nude mouse), and 808nm NIR light was used as the excitation source for in vivo fluorescence imaging, and the mice were imaged at different times with a fluorescence imaging system. Such as Figure 11 As shown, when UBAL was injected into mice bearing 4T1 tumors through the tail vein, obvious fluorescent signals could be seen at the tumor site, and the signal intensity reached the maximum at 2 h. Signal intensity was dim and disap...

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Abstract

The invention discloses near-infrared light-responsive nano-liposomes, a preparation method of the near-infrared light-responsive nano-liposomes, and application in synergetic treatment of tumors. Thenear-infrared light-responsive nano-liposomes are used for obtaining liposomes loaded with up-conversion @ phosphorus through a thin-film hydration method and covalently bound thiol-modified nucleicacid aptamers on the surfaces. The nano-liposomes prepared by the method have the advantageous that near-infrared light energy can be efficiently converted into chemical energy and thermal energy by the nano-liposomes with near-infrared light collection, tumor-targeted photodynamic and photo-thermal synergy treatment is realized, the limitations that single-mode treatment is poor in therapeutic effect, low in tissue penetrability, and poor in selection and recognition abilities in the clinical transformation application of photodiagnosis treatment are discussed. The near-infrared light-responsive nanoliposomes are high in biocompatibility, higher in tumor-specific aggregation ability, and higher in tumor killing effect in in vivo experiments.

Description

technical field [0001] The invention belongs to the field of medical nanomaterials, and in particular relates to a near-infrared light-responsive nanoliposome, a preparation method thereof, and an application in synergistic treatment of tumors. Background technique [0002] Cancer has become one of the major threats to human health due to its high morbidity and mortality. However, due to the characteristics of individual differences and easy metastasis of cancer cells, tumor treatment cannot be cured. Traditional tumor treatment methods, such as chemotherapy, radiotherapy and surgical resection, usually have various side effects during treatment, such as bringing huge trauma to patients. At present, mild non-invasive treatment can effectively destroy tumors with minimal damage to normal tissues and has attracted extensive attention. Among them, photothermodynamic therapy (PTT) and photodynamic therapy (PDT) are two main methods in the non-invasive treatment of malignant tu...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/127A61K47/26A61K41/00A61K49/00A61P35/00
CPCA61K9/1271A61K41/0052A61K41/0057A61K47/26A61K49/0084A61P35/00
Inventor 袁荃梁玲唐娅伟
Owner WUHAN UNIV
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