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Nano diagnosis and treatment agent and preparation method and application thereof

A nano and organic ligand technology, applied in pharmaceutical formulations, medical preparations with non-active ingredients, and medical preparations containing active ingredients, etc., can solve the problems of easy oxidation of ions, low efficiency of tumor chemokinetic treatment, etc. Achieve good photothermal conversion efficiency and improve the effect of

Active Publication Date: 2019-12-13
SHENZHEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] In view of the above-mentioned deficiencies in the prior art, the object of the present invention is to provide a nano-diagnostic agent and its preparation method and application, aiming at solving the problem of existing Fe 2+ Ions are easily oxidized and difficult to deliver directly to the tumor site, resulting in low efficiency of tumor chemokinetic therapy

Method used

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  • Nano diagnosis and treatment agent and preparation method and application thereof
  • Nano diagnosis and treatment agent and preparation method and application thereof
  • Nano diagnosis and treatment agent and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] Embodiment 1: the preparation of organic ligand molecule

[0052] The heptamethine dye IR-823 (100mg, 0.13mmol) and 4-(amino)phenyl 2,2,6,2-terpyridine (100mg, 0.31mmol) were dissolved in anhydrous N,N-dimethylformamide (DMF) (4mL) was stirred at 90°C for 24 hours, cooled to room temperature, spin-dried to remove the solvent, passed through a silica gel column, and eluted with dichloromethane / methanol (25:1, V / V) to obtain a blue-purple solid. That is, the organic ligand molecule.

[0053] figure 2 The H-NMR spectrum of the ligand molecule shows that the organic ligand molecule is consistent with the designed structure, image 3 The mass spectrum of the ligand molecule shows that the molecular weight of the organic ligand molecule is 1023.5, which is consistent with the designed structure.

Embodiment 2

[0054] Embodiment 2: the preparation of nanometer diagnosis and treatment agent

[0055] Dissolve 0.98μmol of organic ligand molecules in 1mL of dichloromethane, first add ferrous ions (1.96μmol), mix well, then add 10mg of DSPE-PEG2000, sonicate for 30s, quickly add 5mL of ultrapure water, and then sonicate for 3min, Dichloromethane was blown out by nitrogen gas, passed through a 220 μm PES membrane, transferred to a 30kD ultrafiltration tube, centrifuged at 3500 rpm, 15 minutes, and 4°C to obtain blue-green nanoparticles (PFNC), that is, the nano-therapeutic agent, see figure 1 shown. Store away from light for later use.

[0056] Figure 4 a is the transmission electron image of the prepared nano-diagnostic agent, which is spherical and has a particle size of about 50nm. Figure 4 b shows that there is no obvious change in the ultraviolet absorption spectrum of the nano-therapeutic agent before and after adding iron ion chelation and before and after self-assembly. Figu...

Embodiment 3

[0057] Example 3: Evaluation of photothermal effect of nano-diagnostic agent

[0058] 808nm laser was used to irradiate the nano-diagnostic agent solution, the concentrations were: 0, 10, 20, 40, 80 μM, and the irradiation power was 1.0 W / cm 2 , and the irradiation time was 5 minutes.

[0059] Figure 6 Represents the photothermal effect curves of different concentrations of nano-therapeutic agents under the same light power irradiation, Figure 6 It can be seen in the 808nm laser at 1.0 W / cm 2 Concentration-dependent under power irradiation. At a concentration of 20 μg / mL, the temperature rises above 45°C after 5 minutes of light irradiation, which is enough to kill tumor cells.

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Abstract

The invention discloses a nano diagnosis and treatment agent as well as a preparation method and an application thereof. The nano diagnosis and treatment agent is formed by self-assembling organic ligand molecules, Fe <2+> and amphiphilic molecules, wherein a structural formula of the organic ligand molecule is shown in the specification,-R is-CH3 or-CH2CH3, the novel organic ligand molecule designed by the invention can keep the stable valence state of Fe <2+>, Fe <2+> is delivered to a tumor site through a nano self-assembly technology, and a chemical kinetic treatment effect is generated. In addition, the organic ligand molecules also have near-infrared photothermal conversion capability, so that the photothermal therapy is realized, and meanwhile, the chemodynamic therapy effect is improved. The novel drug delivery mode provides a new strategy for tumor synergistic treatment.

Description

technical field [0001] The invention relates to the field of nano-medicine, in particular to a nano-diagnostic agent and its preparation method and application. Background technique [0002] Reactive oxygen species (ROS) including superoxide anion (O 2 - ), singlet oxygen ( 1 o 2 ) and hydroxyl radicals (·OH) play vital roles in living organisms. Therapeutic methods that utilize ROS to kill tumor cells include photodynamic therapy (PDT), sonodynamic therapy (SDT) and chemodynamic therapy (CDT). Among them, both PDT and SDT need the participation of photosensitizers and sonosensitizers to generate ROS mainly singlet oxygen to kill tumor cells, while CDT generates hydroxyl free radicals to kill tumor cells with the participation of Fenton's reagent. Among these types of ROS, OH is the most cytotoxic and causes irreversible damage to DNA. Therefore, CDT has the best tumor treatment effect, and it is not limited by the optical penetration depth, and it also has a therapeuti...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/555C07D401/14A61K41/00A61K45/06A61K47/69A61P35/00
CPCA61K41/0052C07D401/14A61K45/06A61K47/6929A61P35/00Y02A50/30
Inventor 林静袁燕燕贺婷黄鹏
Owner SHENZHEN UNIV
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