Preparation method of tumor targeted nanoparticle carrier co-loaded with breast cancer chemotherapeutic drug MTDH siRNA

Abstract

The invention discloses a preparation method of a tumor targeted nanoparticle carrier co-loaded with breast cancer chemotherapeutic drug MTDH siRNA. A PEI-PLGA (polyethyleneimine-poly(lactic-co-glycolic acid)) polymer is dissolved in dichloromethane, deionized water is added, the solution is subjected to ultrasonic crushing and emulsified into a homogenous emulsion, vinyl alcohol, hydrophobic taxol and dichloromethane are mixed and added to the emulsion, the mixture is subjected to ultrasonic crushing and emulsified, the emulsion is evaporated, a nanoparticle suspension is obtained, nanoparticle cores coated with taxol are prepared from the nanoparticle suspension, and then, bleaching, stirring and centrifugation are performed. The breast cancer chemotherapeutic drug and nucleic acid are carried into breast cancer tumor cells with high-expression MTDH genes to inhibit cell proliferation and have significant in-vitro and in-vivo tumor targeting. The carrier has clear anti-tumor effects,used carrier materials have high safety, and the carrier has good biocompatibility and biodegradability and has no biotoxicity or immunogenicity. The preparation process is simple, easy to operate, time-saving, energy-saving and suitable for mass production.

Description

technical field

[0001] The invention belongs to the field of nano-medicines, and in particular relates to a preparation method of tumor-targeting nano-particles co-carrying breast cancer chemotherapeutic drug MTDH siRNA. technical background

[0002] Malignant tumor is an important disease that threatens human health and social development. Its occurrence is a complex process of multi-gene and multi-factor interaction, which eventually leads to abnormal cell proliferation and death. Breast cancer has become the tumor with the highest incidence rate in women, and as a highly heterogeneous tumor, breast cancer has significant differences in pathological typing, molecular typing, and prognosis. Although estrogen receptor-positive breast cancer can benefit from endocrine therapy, chemotherapy still plays an important role in postoperative systemic treatment and treatment of recurrence and metastasis. However, triple-negative breast cancer is highly invasive, prone to recurrence...

Examples

Embodiment 1

[0025] a. After dissolving 18mg polyethyleneimine-lactic acid glycolic acid polymer in 1ml dichloromethane, add 0.2ml deionized water and mix well;

[0026] b. Ultrasonic crush the above solution and emulsify it into a homogeneous emulsion; use the cell disruptor at 25% power for 5 minutes;

[0027] c. After mixing 1.8ml of vinyl alcohol with a mass concentration of 1.8% and 0.2ml of hydrophobic paclitaxel with a mass concentration of 1.8% and 2-4ml of dichloromethane, add it to the above-mentioned emulsion, and then continuously add 10ml of it with a mass concentration of 0.6%. In the state of vinyl alcohol, it was ultrasonically crushed again and then emulsified into a homogeneous emulsion;

[0028] d. After the organic phase in the emulsion prepared in step c is removed with a low-pressure rotary evaporator, the nanoparticle cores loaded with paclitaxel are obtained;

[0029] e. Rinse the paclitaxel-loaded nanoparticle core with deionized water for 5 minutes at 12,000 rpm,...

Embodiment 2

[0036] Embodiment 2: the difference between this embodiment and embodiment 1 is that

[0037] a. After dissolving 20mg polyethyleneimine-lactic acid glycolic acid polymer in 1ml dichloromethane, add 0.25ml deionized water and mix well;

[0038] b. Ultrasonic crush the above solution and emulsify it into a homogeneous emulsion; use the cell disruptor at 25% power for 5 minutes;

[0039] c. After mixing 2.0ml of vinyl alcohol with a mass concentration of 2.0% and 0.25ml of hydrophobic paclitaxel with a mass concentration of 2.0% and 2-4ml of dichloromethane, add it to the above emulsion, and then continuously add 10ml of it with a mass concentration of 0.6%. In the state of vinyl alcohol, it was ultrasonically crushed again and then emulsified into a homogeneous emulsion;

[0040] d. After the organic phase in the emulsion prepared in step c is removed with a low-pressure rotary evaporator, the nanoparticle cores loaded with paclitaxel are obtained;

[0041] e. Rinse the pacli...

Embodiment 3

[0042] Embodiment 3: the difference between this embodiment and embodiment 1 is,

[0043] a. After dissolving 22mg polyethyleneimine-lactic acid glycolic acid polymer in 1ml dichloromethane, add 0.3ml deionized water and mix well;

[0044] b. Ultrasonic crush the above solution and emulsify it into a homogeneous emulsion; use the cell disruptor at 25% power for 5 minutes;

[0045] c. After mixing 1.8-2.2ml of vinyl alcohol with a mass concentration of 2.2% and 0.3ml of hydrophobic paclitaxel with a mass concentration of 2.2% and 2-4ml of dichloromethane, add it to the above-mentioned emulsion, and then continuously add 10ml of it with a mass concentration of In the state of 0.6% vinyl alcohol, it was ultrasonically crushed again and then emulsified into a homogeneous emulsion;

[0046] d. After the organic phase in the emulsion prepared in step c is removed with a low-pressure rotary evaporator, the nanoparticle cores loaded with paclitaxel are obtained;

[0047] e. Rinse th...

technical field

[0001] The invention belongs to the field of nano-medicines, and in particular relates to a preparation method of tumor-targeting nano-particles co-carrying breast cancer chemotherapeutic drug MTDH siRNA. technical background

[0002] Malignant tumor is an important disease that threatens human health and social development. Its occurrence is a complex process of multi-gene and multi-factor interaction, which eventually leads to abnormal cell proliferation and death. Breast cancer has become the tumor with the highest incidence rate in women, and as a highly heterogeneous tumor, breast cancer has significant differences in pathological typing, molecular typing, and prognosis. Although estrogen receptor-positive breast cancer can benefit from endocrine therapy, chemotherapy still plays an important role in postoperative systemic treatment and treatment of recurrence and metastasis. However, triple-negative breast cancer is highly invasive, prone to recurrence...

Examples

Embodiment 1

[0025] a. After dissolving 18mg polyethyleneimine-lactic acid glycolic acid polymer in 1ml dichloromethane, add 0.2ml deionized water and mix well;

[0026] b. Ultrasonic crush the above solution and emulsify it into a homogeneous emulsion; use the cell disruptor at 25% power for 5 minutes;

[0027] c. After mixing 1.8ml of vinyl alcohol with a mass concentration of 1.8% and 0.2ml of hydrophobic paclitaxel with a mass concentration of 1.8% and 2-4ml of dichloromethane, add it to the above-mentioned emulsion, and then continuously add 10ml of it with a mass concentration of 0.6%. In the state of vinyl alcohol, it was ultrasonically crushed again and then emulsified into a homogeneous emulsion;

[0028] d. After the organic phase in the emulsion prepared in step c is removed with a low-pressure rotary evaporator, the nanoparticle cores loaded with paclitaxel are obtained;

[0029] e. Rinse the paclitaxel-loaded nanoparticle core with deionized water for 5 minutes at 12,000 rpm,...

Embodiment 2

[0036] Embodiment 2: the difference between this embodiment and embodiment 1 is that

[0037] a. After dissolving 20mg polyethyleneimine-lactic acid glycolic acid polymer in 1ml dichloromethane, add 0.25ml deionized water and mix well;

[0038] b. Ultrasonic crush the above solution and emulsify it into a homogeneous emulsion; use the cell disruptor at 25% power for 5 minutes;

[0039] c. After mixing 2.0ml of vinyl alcohol with a mass concentration of 2.0% and 0.25ml of hydrophobic paclitaxel with a mass concentration of 2.0% and 2-4ml of dichloromethane, add it to the above emulsion, and then continuously add 10ml of it with a mass concentration of 0.6%. In the state of vinyl alcohol, it was ultrasonically crushed again and then emulsified into a homogeneous emulsion;

[0040] d. After the organic phase in the emulsion prepared in step c is removed with a low-pressure rotary evaporator, the nanoparticle cores loaded with paclitaxel are obtained;

[0041] e. Rinse the pacli...

Embodiment 3

[0042] Embodiment 3: the difference between this embodiment and embodiment 1 is,

[0043] a. After dissolving 22mg polyethyleneimine-lactic acid glycolic acid polymer in 1ml dichloromethane, add 0.3ml deionized water and mix well;

[0044] b. Ultrasonic crush the above solution and emulsify it into a homogeneous emulsion; use the cell disruptor at 25% power for 5 minutes;

[0045] c. After mixing 1.8-2.2ml of vinyl alcohol with a mass concentration of 2.2% and 0.3ml of hydrophobic paclitaxel with a mass concentration of 2.2% and 2-4ml of dichloromethane, add it to the above-mentioned emulsion, and then continuously add 10ml of it with a mass concentration of In the state of 0.6% vinyl alcohol, it was ultrasonically crushed again and then emulsified into a homogeneous emulsion;

[0046] d. After the organic phase in the emulsion prepared in step c is removed with a low-pressure rotary evaporator, the nanoparticle cores loaded with paclitaxel are obtained;

[0047] e. Rinse th...

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