Multicolor up-conversion nanoprobe as well as preparation method and application thereof

Abstract

The invention provides a multicolor up-conversion nanoprobe and a preparation method and an application thereof. The multicolor up-conversion nanoprobe sequentially comprises up-conversion nanoparticles and a silicon dioxide layer from inside to outside, the up-conversion nanoparticle comprises a NaYF4 inner core and a NaYF4 outer shell, and a NaYF4 middle light-emitting layer is arranged betweenthe NaYF4 inner core and the NaYF4 shell; the NaYF4 intermediate light-emitting layer is doped with Y<3+>, Yb<3+>, Tm<3+> and Ho <3+>; wherein multiple photosensitizers are doped between the up-conversion nanoparticles and the silicon dioxide layer and / or in a silicon dioxide layer, the thickness of the silicon dioxide layer is less than 15nm, the outer surface of the silicon dioxide layer is modified with mitochondrial targeting ligands, the multiple photosensitizers comprise at least three photosensitizers, and one of the three photosensitizers is indocyanine green. According to the nanoprobe, through the sensitization effect of ICG and the deep tissue penetrating capacity of 980 nm laser, the prepared nanoprobe based on UCNPs can achieve synergistic PDT treatment on deep tumors.

Description

technical field

[0001] The disclosure belongs to the technical field of biomedicine, and relates to a multi-color up-conversion nano-probe, a preparation method and an application. Background technique

[0002] The statements herein merely provide background information related to the present disclosure and may not necessarily constitute prior art.

[0003] As an exogenous stimulus that can activate hyperthermia, light has the advantages of high spatiotemporal selectivity and few side effects, and has been widely used in photothermal, photodynamic and light-triggered chemical / gene therapy. Photodynamic therapy (PDT) uses photosensitizers (PS) to generate reactive oxygen species (ROSs), which can selectively and irreversibly destroy cancer cells and tumor tissues without damaging adjacent healthy cells. Its clinical application is mainly limited to short tissue penetration depth, easy aggregation of PS molecules and insufficient generation of ROSs.

[0004] Lanthanide-doped...

Examples

Embodiment 1

[0059] Preparation of rare earth oleate:

[0060] Weigh 1.129g (5mmol) Y 2 o 3 In a single-necked round-bottomed flask, measure 20ml of concentrated HCl into the round-bottomed flask, cover with plastic wrap, prick a few small holes with a needle, let it stir at 60°C, react for 8 hours, remove the plastic wrap after 8 hours, Then raise the temperature to 140°C, evaporate the concentrated HCl to get YCl 3 solid. Synthesized YCl 3 Add 10ml of ultrapure water to the solid, ultrasonically dissolve, then add 5ml of ultrapure water, and filter YCl with a syringe with a filter head 3 The solution was injected into another clean and dry flask, and then 20ml of ethanol, 35ml of n-hexane, and 30mmol of sodium oleate were added, and refluxed at 78°C for 4h. After the reaction, cool down to 30-40°C, transfer the solution to a separatory funnel for extraction, remove the lower layer of the solution after layering, add 20ml of water and 20ml of ethanol, oscillate and shake well, extract ...

Embodiment 2

[0069] This example is the same as Example 1, except that the molar ratio of Y:Yb:Tm:Ho in UCNPs is 77.8:20:0.2:2.

Embodiment 3

[0071] This example is the same as Example 1, except that the concentrations in the HA ethanol solution, ICG ethanol solution and MB aqueous solution are all 2.0 mg / mL.

technical field

[0001] The disclosure belongs to the technical field of biomedicine, and relates to a multi-color up-conversion nano-probe, a preparation method and an application. Background technique

[0002] The statements herein merely provide background information related to the present disclosure and may not necessarily constitute prior art.

[0003] As an exogenous stimulus that can activate hyperthermia, light has the advantages of high spatiotemporal selectivity and few side effects, and has been widely used in photothermal, photodynamic and light-triggered chemical / gene therapy. Photodynamic therapy (PDT) uses photosensitizers (PS) to generate reactive oxygen species (ROSs), which can selectively and irreversibly destroy cancer cells and tumor tissues without damaging adjacent healthy cells. Its clinical application is mainly limited to short tissue penetration depth, easy aggregation of PS molecules and insufficient generation of ROSs.

[0004] Lanthanide-doped...

Examples

Embodiment 1

[0059] Preparation of rare earth oleate:

[0060] Weigh 1.129g (5mmol) Y 2 o 3 In a single-necked round-bottomed flask, measure 20ml of concentrated HCl into the round-bottomed flask, cover with plastic wrap, prick a few small holes with a needle, let it stir at 60°C, react for 8 hours, remove the plastic wrap after 8 hours, Then raise the temperature to 140°C, evaporate the concentrated HCl to get YCl 3 solid. Synthesized YCl 3 Add 10ml of ultrapure water to the solid, ultrasonically dissolve, then add 5ml of ultrapure water, and filter YCl with a syringe with a filter head 3 The solution was injected into another clean and dry flask, and then 20ml of ethanol, 35ml of n-hexane, and 30mmol of sodium oleate were added, and refluxed at 78°C for 4h. After the reaction, cool down to 30-40°C, transfer the solution to a separatory funnel for extraction, remove the lower layer of the solution after layering, add 20ml of water and 20ml of ethanol, oscillate and shake well, extract ...

Embodiment 2

[0069] This example is the same as Example 1, except that the molar ratio of Y:Yb:Tm:Ho in UCNPs is 77.8:20:0.2:2.

Embodiment 3

[0071] This example is the same as Example 1, except that the concentrations in the HA ethanol solution, ICG ethanol solution and MB aqueous solution are all 2.0 mg / mL.

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