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Dual-response nanodrug delivery system loaded with antitumor drugs for tumor therapy and preparation method of nanodrug delivery system

A technology of anti-tumor drugs and nano-drugs, which is applied in the direction of anti-tumor drugs, drug combinations, drug delivery, etc., and can solve the problems of reduced anti-tumor effect, weakened drug effect of doxorubicin, and reduced drug effect of doxorubicin

Active Publication Date: 2019-07-23
NANKAI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, compared with free doxorubicin (IC50=0.18 μg / mL), the IC50 of this gel loaded with doxorubicin on tumor cell Hela was 0.26 μg / mL, and the efficacy of doxorubicin was reduced by 44%
This shows that when the pH-responsive sodium alginate nanogel reduces the toxic side effects on normal cells, it also weakens the drug effect of doxorubicin, which greatly reduces the anti-tumor effect of the gel

Method used

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  • Dual-response nanodrug delivery system loaded with antitumor drugs for tumor therapy and preparation method of nanodrug delivery system
  • Dual-response nanodrug delivery system loaded with antitumor drugs for tumor therapy and preparation method of nanodrug delivery system
  • Dual-response nanodrug delivery system loaded with antitumor drugs for tumor therapy and preparation method of nanodrug delivery system

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Experimental program
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Embodiment 1

[0037] Example 1: Preparation of a dual-responsive anti-tumor drug-loaded nano-drug delivery carrier for tumor treatment:

[0038] Preparation of oxidized sodium alginate (OSA) by sodium periodate reduction method: Weigh 2 g of sodium alginate (C 5 h 7 o 4 COONa) was dissolved in 120 mL of deionized water, then 20 mL of sodium periodate (NaIO4) solution (n(SA):n(NaIO4)=1:1) was added, and 60 mL of deionized water was added again. After 24 hours of stirring and reacting in the dark, 0.7 mL of absolute ethanol was added, and stirring was continued for 30 minutes to terminate the reaction. The resulting crude product was dissolved in 100 mL of deionized water, and the product was purified by precipitation with acetone. After three times of purification, the crude product was washed with ethanol, and finally OSA was obtained by suction filtration.

[0039] Prepared from ethylenediamine and 11-mercaptoundecanoic acid (C 11 h 22 o 2 Aliphatic amines formed by S, MUA) coupling...

Embodiment 2

[0046] Embodiment 2: Research on the drug release behavior of simulated nanoparticles in vitro:

[0047] The in vitro release profiles of antitumor drugs in DSA / CC were investigated in phosphate buffer solution (pH 7.4 and 5.7) with or without 10 mM GSH. First, 2 mg DSA / CC was dissolved in 4 mL buffer solution and transferred to a dialysis bag (MW = 3500 Da), then the dialysis bag was placed in a 50 mL centrifuge tube filled with release medium and dialyzed at 37 °C. At set time intervals, 0.2 mL samples were withdrawn and replaced with an equal volume of release medium. Finally, use the EnspireTM multifunctional microplate reader (excitation 480nm, emission 588nm) to measure the amount of antitumor drug released in the sample, see figure 1 .

Embodiment 3

[0048] Embodiment 3: Intracellular antitumor drug release monitoring:

[0049] A live-cell imaging system was used to observe the intracellular release of antitumor drugs. Cells (HepG2 and LO2) were divided into 1×10 5 The density of cells / well was inoculated on the bottom of a glass dish, 2 mL of 1640 medium (10% fetal bovine serum + 1% penicillin-streptomycin) was added, and incubated in an incubator for 24 hours (37°C, 5% CO 2 ), carefully aspirate the medium, wash twice with PBS, and use 1 mL of DSA / CC-containing medium (25 μg mL -1 )replace. The cells were then incubated for 2 hours in the Live Cell Workstation, set to take pictures every 10 minutes, see figure 2 .

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Abstract

The invention relates to a dual-response nanodrug delivery system loaded with antitumor drugs for tumor therapy and a preparation method of the nanodrug delivery system. Sodium alginate modified with11-mercaptodecanoic acid (MUA) is used as a frame, CaCO3 and antitumor drugs are coprecipitated on the frame of sodium alginate by in-situ mineralization, and through ultrasonic vibration, sulfhydrylgroups on the modified sodium alginate are promoted to be crosslinked to prepare a dual-response nanodrug delivery carrier of pH and redox. According to the present invention, in vivo and in vitro drug release, cytotoxicity experiments and animal experiments prove that nanoparticles based on CaCO3 have good tumor selectivity and the ability of regulating pH in tumor cells, and can kill and wound tumor cells while reducing toxic and side effects on normal cells and organisms. The nanodrug delivery carrier provided by the invention is expected to be used for tumor therapy, and has a good application prospect in the field of biomedicine.

Description

[0001] Technical field: [0002] The invention relates to a nano-drug delivery system and a preparation method of a double-responsive anti-tumor drug-carrying drug delivery system for tumor treatment. [0003] Background technique: [0004] Malignant tumors are characterized by difficulty in early diagnosis, high degree of malignancy, strong invasiveness, and short survival period of patients. Currently, chemotherapy is the most important means of tumor intervention besides surgery. Common chemotherapeutic drugs used for tumors include 5-fluoropyrimidine, cisplatin, paclitaxel, antineoplastic drugs, etc. Weakly basic drugs, such as antineoplastic drugs, are protonated outside the cell and are difficult to enter tumor cells. In addition, a small amount of weakly basic drugs that can enter cells are trapped in acidic vesicles and cannot exert their drug effect (Fais S, DeMilito A, You H, et al.Targeting vacuolar H + -ATPases as a new strategy against cancer [J]. Cancer Researc...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/61A61K47/52A61K47/69A61K31/704A61K31/475A61P35/00C08B37/04
CPCA61K47/61A61K47/52A61K47/6939A61K47/6923A61K31/704A61K31/475A61P35/00C08B37/0084
Inventor 王永健于奡张晨旭
Owner NANKAI UNIV
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