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PH-responsive mesoporous silicon nanoparticle treatment vaccine based on co-entrapped antigen and photosensitizer as well as preparation method and application thereof

A technology of mesoporous silicon nanoparticles and therapeutic vaccines, applied in the field of therapeutic vaccines, can solve the problems of poor curative effect and multiple immunizations, and achieve the effects of low cost, elimination of in situ tumors, and simple surface modification

Active Publication Date: 2020-11-24
INST OF BIOMEDICAL ENG CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] At present, although the emphasis on vaccine combined with PTT in the treatment of tumors has increased, there are still some problems, such as: 1) multiple immunizations are required; 2) even if combined with antibody treatment, less effective

Method used

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  • PH-responsive mesoporous silicon nanoparticle treatment vaccine based on co-entrapped antigen and photosensitizer as well as preparation method and application thereof
  • PH-responsive mesoporous silicon nanoparticle treatment vaccine based on co-entrapped antigen and photosensitizer as well as preparation method and application thereof
  • PH-responsive mesoporous silicon nanoparticle treatment vaccine based on co-entrapped antigen and photosensitizer as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0072] This embodiment provides a pH-responsive therapeutic vaccine based on mesoporous silicon nanoparticles that co-encapsulate antigens and photosensitizers. The preparation method includes steps:

[0073] S1: Weigh 25 mg of mesoporous silicon nanoparticles (MSNs) into 5 mL of 2M ammonium bicarbonate solution, and in an ice bath, use a 3 mm probe and an ultrasonic cell disruptor with a power of 30% to sonicate for 5 minutes (sonication for 5 seconds and stop for 3 seconds) , to obtain a nanoparticle solution, continue to incubate at 4° C. with shaking overnight (>10 h), then centrifuge at 15,000 rpm for 10 min, wash twice with deionized water, and collect the precipitate.

[0074] S2: Resuspend the above precipitate with 1mL Tris-HCl solution (10mM, pH 8.5), then add 4mL Tris-HCl solution (10mM, pH 8.5) containing 25mg dopamine hydrochloride under shaking conditions, and continue shaking for 6h under dark conditions Above, centrifuge at 15000rpm for 10min, wash twice with d...

experiment example 1

[0091] 1. Particle size and potential measurement

[0092] figure 1 a and b are the particle size and Zeta potential diagrams of MSNs, MSNs@PDA, MSNs-ABC@PDA, MSNs@PDA-OVA and MSNs-ABC@PDA-OVA, respectively; figure 1 c in PBS, free OVA, MSNs-ABC@PDA, MSNs@PDA-OVA and MSNs-ABC@PDA-OVA in 808nm laser (2.5W / cm 2 , 5min) under the temperature rise curve; figure 1 d, e and f are the cumulative antigen release curves of MSNs@PDA-OVA and MSNs-ABC@PDA-OVA under laser irradiation or without laser irradiation in PBS release solution with pH 7.4, 6.5 and 5.0, respectively .

[0093] For details on particle size, see figure 1 In a, the result shows that the average particle size of the prepared vaccine based on mesoporous silicon nanoparticles is below 300nm; the results of the potential measurement are shown in figure 1 In b, the results show that the prepared mesoporous silicon nanoparticle-based vaccine has a stable negative potential value.

[0094] 2. Encapsulation efficiency o...

experiment example 2

[0106] 1. Photothermal toxicity of the pH-responsive therapeutic vaccine (MSNs-ABC@PDA-OVA) based on mesoporous silicon nanoparticles co-encapsulating antigens and photosensitizers prepared in Example 1 of the present invention on B16-OVA tumor cells detection

[0107] B16-OVA cells were seeded into 96-well plates (10 per well 3 cells) were cultured overnight, then the culture medium was discarded, and 100 μL of PBS, free OVA, MSNs-ABC@PDA, MSNs-ABC@PDA-OVA and MSNs-ABC@PDA-OVA (the equivalent OVA concentration was 25 μg / mL) were added respectively. Culture medium continued to grow. After incubation for 2 h, the cells were irradiated with 808 nm laser light with different power intensities for 5 min. After further incubation for 22 h, the cells were washed with PBS and added to 100 μL RPMI1640 medium containing 20 μL MTS for 30 min. Measure the absorbance at 490nm with a microplate reader, and calculate the cell viability according to the following formula:

[0108] Cell su...

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Abstract

The invention provides a pH-responsive mesoporous silicon nanoparticle treatment vaccine based on a co-entrapped antigen and a photosensitizer as well as a preparation method and an application thereof, and relates to the technical field of treatment vaccine; the inventor designs a nano platform, mesoporous silicon dioxide nanoparticles are used as a carrier, co-loaded photo-thermal treatment agent dopamine and sulfhydrylated antigen are used for photo-thermal combined immune treatment of tumors. According to the preparation method provided by the invention, the pH-responsive mesoporous silicon nanoparticle treatment vaccine based on the co-entrapped antigen and the photosensitizer is obtained, and the antigen entrapment rate is up to 92.20%. Meanwhile, the preparation method is simple inprocess, convenient to operate, capable of being achieved without expensive instruments or high-end technicians, low in cost and suitable for application and popularization.

Description

technical field [0001] The invention relates to the technical field of therapeutic vaccines, in particular to a pH-responsive therapeutic vaccine based on mesoporous silicon nanoparticles co-encapsulating antigens and photosensitizers, as well as its preparation method and application. Background technique [0002] Cancer remains an urgent worldwide problem due to high morbidity and mortality. Therefore, the development of effective cancer therapies that can eliminate solid tumors and metastatic tumors while preventing tumor recurrence is an urgent priority. Cancer immunotherapy has revolutionized cancer therapy and is recognized as an effective clinical therapy by activating cytotoxic T lymphocytes (CTLs), secreting IFN-γ and suppressing immunosuppressive regulatory T cells (Tregs) to attack and the goal of eliminating all tumor cells, generating enhanced immune memory and preventing tumor recurrence. In particular, cancer vaccines have emerged as a promising approach for...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K41/00A61K9/52A61K47/04A61P35/00A61K39/00
CPCA61K41/0057A61K41/0052A61K39/0011A61K9/5115A61P35/00A61K2300/00Y02A50/30
Inventor 朱敦皖黄晨露张琳华马桂蕾吕丰刘兰霞董霞
Owner INST OF BIOMEDICAL ENG CHINESE ACAD OF MEDICAL SCI
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