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Nano-drug delivery system and preparation method of dual-responsive anti-tumor drug loaded for tumor treatment

A technology of anti-tumor drugs and nano-drugs, which is applied in the direction of anti-tumor drugs, drug combinations, drug delivery, etc., can solve the problems of reduced efficacy of doxorubicin, reduced effect of tumor inhibition, weakened efficacy of doxorubicin, etc., to achieve rich The effect of increasing concentration, increasing tumor inhibition rate and avoiding leakage

Active Publication Date: 2022-03-29
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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  • Nano-drug delivery system and preparation method of dual-responsive anti-tumor drug loaded for tumor treatment
  • Nano-drug delivery system and preparation method of dual-responsive anti-tumor drug loaded for tumor treatment
  • Nano-drug delivery system and preparation method of dual-responsive anti-tumor drug loaded for tumor treatment

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Example 1: Preparation of dual-responsive anti-tumor drug-loaded nano-drug delivery carrier for tumor treatment:

[0036] 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, followed by the addition of 20 mL of sodium periodate (NaIO 4 ) solution (n(SA): n(NaIO 4 ) = 1 : 1), add 60 mL of deionized water again. After stirring the reaction in the dark for 24 hours, 0.7 mL of absolute ethanol was added, and the reaction was continued to stir for 30 minutes to terminate the reaction. The resulting crude product was dissolved in 100 mL of deionized water and purified by precipitation with acetone. After 3 times of purification, the crude product was washed with ethanol, and finally OSA was obtained by suction filtration.

[0037] Prepared from ethylenediamine and 11-mercaptoundecanoic acid (C 11 H 22 O 2 S, MUA) coupling to form aliphatic amin...

Embodiment 2

[0044] Example 2: Study on drug release behavior of simulated nanoparticles in vitro:

[0045] The in vitro release profiles of antineoplastic drugs in DSA / CC were investigated in phosphate buffered solutions (pH 7.4 and 5.7) with or without 10 mM GSH. First, 2 mg of DSA / CC was dissolved in 4 mL of buffer solution and transferred to a dialysis bag (MW = 3500 Da), then the dialysis bag was placed in a 50 mL centrifuge tube with release medium at 37 °C. Dialysis. At set time intervals, 0.2 mL samples were withdrawn and replaced with an equal volume of release medium. Finally, the amount of antineoplastic drug released in the samples was determined using an EnspireTM multi-plate reader (excitation 480 nm, emission 588 nm), see figure 1 .

Embodiment 3

[0046] Example 3: Intracellular antitumor drug release monitoring:

[0047] The intracellular release of antitumor drugs was observed by live cell imaging system. Cells (HepG2 and LO2) were divided into 1 x 10 5 Cells / well were seeded to the bottom of a glass dish, 2 mL of 1640 medium (10% fetal bovine serum + 1% penicillin-streptomycin) was added, and the cells were incubated in an incubator (37°C, 5% CO) for 24 hours. 2 ), carefully aspirate the medium, wash twice with PBS, and add 1 mL of DSA / CC-containing medium (25 μg mL -1 )replace. Cells were then incubated in the live cell workstation for 2 hours, set to capture every 10 minutes, see figure 2 .

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Abstract

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. Sodium alginate modified with 11‑mercaptoundecanoic acid (MUA) was used as the backbone to make CaCO 3 Co-precipitate with anti-tumor drugs on the sodium alginate skeleton, and use ultrasonic vibration to promote the cross-linking of sulfhydryl groups on the modified sodium alginate to prepare pH and redox dual-responsive nano-drug delivery carriers. The present invention proves that the CaCO-based 3 The nanoparticles have good tumor selectivity and the ability to regulate the pH of tumor cells, which can reduce the toxic and side effects on normal cells and the body while killing tumor cells. The nano drug delivery carrier provided by the invention is expected to be used for tumor treatment, and has a good application prospect in the field of biomedicine.

Description

technical field [0001] The invention relates to a dual-responsive anti-tumor drug-carrying nano drug delivery system for tumor treatment and a preparation method. Background technique [0002] Malignant tumors have the characteristics of difficult early diagnosis, high malignancy, strong invasiveness, and short survival time of patients. At present, chemotherapy is the most important tumor intervention in addition to surgery. Common chemotherapeutic drugs for tumors include 5-fluoropyrimidine, cisplatin, paclitaxel, and antitumor drugs. Weakly basic drugs, such as antitumor drugs, are protonated outside the cell and are difficult to enter into tumor cells. In addition, a small amount of weakly basic drugs that can enter cells are trapped in acidic vesicles and cannot exert their efficacy (Fais S, DeMilito A, You H, et al. Targeting vacuolar H + -ATPases as a new strategyagainst cancer[J]. Cancer Research, 2007, 67(22): 10627–10630). Ultimately, tumor cells become less se...

Claims

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Application Information

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Patent Type & Authority Patents(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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