Nitric oxide-responsive amphiphilic conjugated oligomer and preparation method thereof

Abstract

The application discloses a kind of nitric oxide response amphiphilic conjugated oligomer and preparation method thereof.The nitric oxide response amphiphilic conjugated oligomer described in the application forms nanoparticle by self-assembly, and after reaction with NO, its absorption spectrum is red-shifted, fluorescence is enhanced, has stronger photothermal effect, and by modifying its hydrophilic side chain group, self-assembly forms nanoparticle, has water-solubility, stronger photothermal effect and NO reaction performance, has very broad application prospect in biomedical field.

Description

Technical Field

[0001] This invention belongs to the field of materials, specifically relating to a nitric oxide-responsive amphiphilic conjugated oligomer and its preparation method, as well as nanoparticles formed based on the conjugated oligomer. Background Technology

[0002] Conjugated oligomers are a class of conjugated molecules composed of multiple monomers coupled or polymerized, possessing a π-conjugated structural backbone. Conjugated oligomers exhibit similar structural composition and optical properties to conjugated polymers, such as strong photostability, high light absorption factors, and high photothermal conversion efficiency. Furthermore, their energy levels can be tuned through structural design, thereby controlling their absorption characteristics of infrared light in the near-infrared band. Compared to conjugated polymers, oligomers also offer advantages such as well-defined structures, ease of preparation and purification, and good solubility. Compared to some small-molecule dyes or monomers, conjugated oligomers exhibit a redshift in their absorption spectra and significantly increased photostability. Therefore, developing conjugated oligomers with narrower band gaps, higher photothermal conversion efficiency, and stronger photostability holds immense potential value for biological applications.

[0003] Currently, common methods involve encapsulating conjugated polymers with biocompatible amphiphilic polymers using dispersion methods to form nanoparticles with strong water dispersibility and good biocompatibility. However, these nanoparticles have certain limitations, such as low encapsulation efficiency, easy dissociation, short cycle time, and poor biocompatibility. In contrast, conjugated oligomers, due to their easily modifiable side chains (e.g., benzothiadiazole core chromophore is an important near-infrared II (NIR-II) dye, suffer from fluorescence quenching and inactivation limitations in aqueous media, which are major obstacles to their biological applications), can be designed as SDADS-type conjugated oligomers to protect their fluorescence from quenching. Furthermore, hydrophilic groups can be grafted onto the side chains of conjugated oligomers, utilizing their hydrophilic and hydrophobic properties to allow them to spontaneously assemble into stable and water-soluble nanoparticles without further processing.

[0004] Endogenous nitric oxide (NO) plays a vital physiological role in organisms. In humans and animals, it is essential for bodily systems such as the nervous, cardiovascular, and immune systems, as well as for many chronic diseases and conditions, including chronic inflammation, erectile dysfunction, and liver disease. In plants, it is a crucial regulatory molecule for development and morphogenesis, acting as a signaling molecule at every stage of the plant life cycle and playing a key role in plant disease development. This has prompted researchers to focus on using nitric oxide as a diagnostic biomarker and a potential target for medical treatment. Like many other important compounds, NO is a double-edged sword. When produced in adequate amounts in vivo or in plants, it is essential for maintaining health. However, if excessive, it becomes harmful. Therefore, accurate detection of nitric oxide in humans or plants is of great significance. Summary of the Invention

[0005] One of the objectives of this invention is to provide amphiphilic conjugated oligomer-based nanoparticles with nitric oxide-stimulated responsiveness.

[0006] The amphiphilic conjugated oligomer-based nanoparticles with nitric oxide-responsive properties provided by this invention can change their ultraviolet absorption characteristics when NO is present in aqueous solution, showing a new absorption peak at 500-700 nm, and can produce photothermal effect or fluorescence under near-infrared light irradiation in this wavelength range.

[0007] The amphiphilic conjugated oligomer-based nanoparticles provided by this invention are self-assembled from the amphiphilic conjugated oligomers shown in Formula I.

[0008]

[0009] In Formula I, the Acceptor is the following group:

[0010]

[0011] Donor is one of the following groups:

[0012]

[0013] Where a is an integer from 2 to 5, specifically 3; b is an integer from 5 to 10, specifically 7; c is an integer from 5 to 10, specifically 7.

[0014] The shielding unit is at least one of the following groups:

[0015]

[0016] Where d, e, f, g, h, and l are each an integer from 1 to 10, specifically 5;

[0017] R1, R2, R3, R4, R5, and R6 are each independently selected from:

[0018]

[0019] R7 is H, C1-C6 alkyl; n = 40-50; R8, R9, R 10 Each is independently selected from C1-C6 alkyl groups, and X is a halide anion (F-, Cl-, Br-). - I - ), or acid radical (HSO) -4 RCOO - wait).

[0020] Specifically, the amphiphilic conjugated oligomers shown in Formula I above are the following compounds:

[0021]

[0022] n = 40-50.

[0023] The above-mentioned amphiphilic conjugated oligomer-based nanoparticles were prepared by a method comprising the following steps:

[0024] 1) Dissolve the amphiphilic conjugated oligomer shown in Formula I in an organic solvent miscible with water and then sonicate it.

[0025] 2) The obtained mixture was added to ultrapure water, and nanoparticles were prepared by ultrasonic self-assembly. Inert gas was bubbled into the solution until all organic solvent evaporated to obtain an aqueous solution of nanoparticles.

[0026] 3) The aqueous solution of the obtained nanoparticles was treated by dialysis to obtain amphiphilic conjugated oligomer-based nanoparticles.

[0027] In step 1) of the above method, the organic solvent may specifically be tetrahydrofuran, and the ultrasonic treatment time may be 10-60 min;

[0028] In step 2) of the above method, the volume ratio of the mixture to ultrapure water can be 1:2 to 1:10, specifically 1:5;

[0029] The inert gas may specifically be nitrogen and / or argon;

[0030] In step 3) of the above method, the molecular weight cutoff of the dialysis bag is 1000D.

[0031] The second objective of this invention is to provide the application of the above-mentioned amphiphilic conjugated oligomers and amphiphilic conjugated oligomer-based nanoparticles in the detection of nitric oxide.

[0032] After the above-mentioned amphiphilic conjugated oligomers or amphiphilic conjugated oligomer-based nanoparticles react with NO, the chemical structure of their acceptor units changes, and their ultraviolet absorption characteristics change. A new absorption peak appears at 500-700 nm, and they can produce photothermal effects or fluorescence under near-infrared light irradiation in this wavelength range. Their absorption shifts to the near-infrared region, exhibiting a good photothermal effect.

[0033] The present invention also provides a method for detecting the presence of nitric oxide in a system.

[0034] The method for detecting the presence of nitric oxide in a system provided by the present invention includes the following steps: contacting the amphiphilic conjugated oligomer-based nanoparticles with the system to be tested; if the ultraviolet absorption characteristics of the resulting system change, that is, a new absorption peak appears at 500-700 nm, then the system is determined to contain nitric oxide; or irradiating the resulting system with near-infrared light in the wavelength range of 500-700 nm, if the system produces a photothermal effect or enhanced fluorescence, then the system is determined to contain nitric oxide; otherwise, the system does not contain nitric oxide.

[0035] Compared with the prior art, the advantages of the present invention are as follows:

[0036] 1. The synthesis method is simple and mature, with a short synthetic route, high reaction yield, and is simple and efficient; the raw materials are commercial products and can be widely used in industrial synthesis.

[0037] 2. The structure of the conjugated oligomers is determined and can be accurately characterized;

[0038] 3. Compared to small molecules, this oligomer exhibits a red shift in its absorption spectrum, resulting in a stronger photothermal effect; compared to high molecular weight polymers, it possesses the advantages of strong photothermal effect while overcoming the drawbacks of batch synthesis and poor solubility in high molecular weight polymers.

[0039] 4. This conjugated oligomer has amphiphilic and self-assembly effects. By modifying the hydrophilic side chain groups, it can be self-assembled into nanoparticles using hydrophobic interactions, and then into water-soluble nanomaterials with photothermal effects. Its shielding unit protects its fluorescence from being quenched.

[0040] 5. The nitric oxide-responsive amphiphilic conjugated oligomers of the present invention form nanoparticles through self-assembly. After reacting with NO, their absorption spectrum red-shifts, fluorescence is enhanced, and they exhibit a stronger photothermal effect. Furthermore, by modifying their hydrophilic side chain groups, they self-assemble into nanoparticles, which are water-soluble, have a strong photothermal effect, and NO-reactive properties, thus showing very broad application prospects in the biomedical field.

[0041] This invention discloses a novel synthetic method for nitric oxide-responsive amphiphilic conjugated oligomers and their properties in reaction with NO. The nitric oxide-responsive amphiphilic conjugated oligomers are synthesized into nanoparticles through conjugation reactions of conjugated molecules, quaternization reactions with different functional groups, and modification of side chains with PEG. Furthermore, their reaction with NO causes a red shift in their absorption spectrum and enhanced fluorescence, demonstrating significant potential for biological applications. The conjugated oligomer nanoparticles of this invention can be used to detect nitric oxide in vivo. Attached Figure Description

[0042] Figure 1 This is a synthetic route diagram for preparing the compound of formula I in Example 1 of the present invention.

[0043] Figure 2 The UV-Vis absorption spectrum of the IFE-NH2-NPs nanoparticles prepared in Example 2 of this invention is shown.

[0044] Figure 3 The infrared spectra of the nanoparticles IFE-Br2, IFE-N3, and IEG-NH2-NPs prepared in Example 3 of this invention are shown.

[0045] Figure 4 The particle size characterization of the IFE-NH2-NPs nanoparticles prepared in Example 2 of this invention.

[0046] Figure 5 The UV-Vis absorption spectra of the IFE-NH2-NPs / NO nanoparticles prepared in Example 4 of this invention are characterized.

[0047] Figure 6 The fluorescence excitation spectrum (650 nm excitation) of the IFE-NH2-NPs / NO nanoparticles prepared in Example 4 of this invention is shown.

[0048] Figure 7 The UV-Vis absorption spectra of the nanoparticles IEG-N3 prepared in Example 3 of this invention before and after reaction with nitric oxide are shown.

[0049] Figure 8 The UV-Vis absorption spectra of the IEG-NH2-NPs nanoparticles prepared in Example 3 of this invention before and after reaction with nitric oxide are shown.

[0050] Figure 9 Photothermal effect diagrams of IFE-NH2-NPs nanoparticles / NO obtained by the reaction of IFE-NH2-NPs with NO at different concentrations (0 mg / mL, 0.10 mg / mL, 0.15 mg / mL, 0.20 mg / mL, 0.30 mg / mL, 0.40 mg / mL). Detailed Implementation

[0051] The present invention will now be described in further detail with reference to specific embodiments. The given embodiments are merely illustrative of the invention and not intended to limit its scope. The embodiments provided below can serve as a guide for further improvements by those skilled in the art and do not constitute a limitation on the invention in any way.

[0052] Unless otherwise specified, the experimental methods used in the following examples are conventional methods, performed according to the techniques or conditions described in the literature in this field or according to the product instructions. Unless otherwise specified, the materials and reagents used in the following examples are commercially available.

[0053] Example 1: Synthesis of nitric oxide-responsive amphiphilic conjugated oligomers IFE-NH2 and IEG-NH2 according to Figure 1 The synthetic route shown was used to prepare the compound IFE-NH2.

[0054] 1) Synthesis of tributyl(2,3-dihydrothiopheno[3,4-B]-[1,4]dioxin-5-yl)stanane

[0055] 3,4-Ethylenedioxothiophene (8.45 g, 59.43 mmol) was dissolved in 100 mL of anhydrous tetrahydrofuran under argon atmosphere. The solution was cooled to -78 °C, and 26 mL of n-butyllithium (62.4 mmol, 2.4 M) was added over 1 hour. After stirring at -78 °C for 1 hour, the temperature was raised to -20 °C and reacted for 1 hour. Then, tributyltin chloride (21.28 g, 65.37 mmol) was added dropwise over 30 minutes at -78 °C. After the addition, the resulting mixture was stirred at -78 °C for another 1 hour, and then allowed to slowly warm to room temperature and react overnight. The mixture was then poured into 100 mL of water, extracted with dichloromethane, and the resulting organic layer was dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure without further purification.

[0056] 2) Synthesis of 5-(9H-fluorene-2-yl)-2,3-dihydrothiophene[3,4-b][1,4]dioxane

[0057] 2-Bromo-9H-fluorene (5.0 g, 20.4 mmol) and tributyl(2,3-dihydrothieno[3,4-B]-[1,4]dioxin-5-yl)stanane (9.2 g, 21.4 mmol) were dissolved in toluene (40 mL) under a protective atmosphere, followed by the addition of Pd(PPh3)4 (200 mg). After reflux at 110 °C for 24 h, the reaction mixture was cooled to room temperature and extracted with a saturated aqueous solution of potassium fluoride and dichloromethane. The mixture was then dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. Finally, the crude product was subjected to column chromatography on silica gel (petroleum ether: dichloromethane = 1:7) to give 2.75 g of a pale yellow solid, with a yield of 62.08%.

[0058] The structural characterization data are as follows:

[0059] Mass spectrometry: HRMS (ESI) [M+Na+] m / z: 329.0605

[0060] 1H NMR spectrum: 1H NMR (400MHz, Chloroform-d) δ 7.85 (s, 1H), 7.66 (d, J = 7.2Hz, 3H), 7.43 (d, J = 7.4Hz, 1H), 7.26 (d, J = 15.1Hz, 1H), 7.17 (dd, J = 16.0, 8.6Hz, 1H), 5.18 (s, 3H), 4.34 (s, 2H), 3.83 (s, 2H), 1.43 (s, 1H), 1.14 (s, 2H).

[0061] 3) Synthesis of 5-(9,9-bis(6-bromohexyl)-9H-fluorene-2-yl)-2,3-dihydrothiophene[3,4-b][1,4]dioxane

[0062] 5-(9H-fluorene-2-yl)-2,3-dihydrothiophene[3,4-b][1,4]dioxane (3.0 g, 9.8 mmol) and 1,6-dibromohexane (9.7 g, 40 mmol) were dissolved in 50 mL of THF at 0 °C. Then, 2.5 g (2.1 mmol) of potassium tert-butyrate in THF was added dropwise. After stirring overnight at room temperature, the reaction mixture was extracted with water and dichloromethane, dried over anhydrous sodium sulfate, and the solvent was removed by vacuum distillation. The crude product was subjected to column chromatography on silica gel (petroleum ether: ethyl acetate = 1:6) to give 4.35 g of a pale yellow oil, in a yield of 70.27%.

[0063] The structural characterization data are as follows:

[0064] Mass spectrometry: HRMS (ESI) [M+Na+] m / z: 655.0705

[0065] 1H NMR spectrum: 1H NMR (400MHz, Chloroform-d) δ 7.67 (d, J = 8.0Hz, 1H), 7.65–7.60 (m, 2H), 7.58 (s, 1H), 7.32–7.18 (m, 3H), 4.07 (q, J = 7.2Hz, 0H), 3.22 (t, J = 6.7Hz, 6H), 1.83 (s, 32H), 1.60 (t, J = 7.3Hz, 4H), 1.43 (h, J = 3.4, 2.7Hz, 55H), 1.18 (d, J = 24.9Hz, 2H), 1.02 (s, 2H), 0.81 (s, 1H), 0.61 (d, J = 8.4Hz, 2H).

[0066] 4) Synthesis of IFE-NO2

[0067] 5-(9,9-bis(6-bromohexyl)-9H-fluoren-2-yl)-2,3-dihydrothiophene[3,4-b][1,4]dioxane (2.0 g, 3.18 mmol) was dissolved in 25 mL of anhydrous tetrahydrofuran under argon protection. Then, n-butyllithium (2.4 M, 3.8 mmol) was added dropwise to the reaction system at -78 °C. After stirring at this temperature for 1.5 hours, tributyltin chloride (1.3 g, 3.8 mmol) was added. The reaction mixture was slowly heated to room temperature and stirred overnight. The mixture was then poured into water and extracted twice with ethyl acetate. The resulting organic phase was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure without further purification. Compound 4,7-dibromo-5,6-dinitrobenzo[c][1,2,5]thiadiazole (192 mg, 0.5 mmol) and the above crude product (1.4 g, 1.56 mmol) were dissolved in toluene solution (15 mL) under a protective atmosphere. Then, Pd(PPh3)2Cl2 (100 mg) was added, and the mixture was stirred at 110 °C for 12 hours. After cooling to room temperature, the mixture was poured into water and extracted twice with ethyl acetate. The extract was then dried over anhydrous sodium sulfate and evaporated under vacuum. The crude product was subjected to silica gel column chromatography (petroleum ether: ethyl acetate = 2:1) to give a deep purple product IFE-NO2 273 mg, with a yield of 35.7%.

[0068] The structural characterization data are as follows:

[0069] Mass spectrometry: [HR-MS (TOF)] m / z: 1486.1048

[0070] ¹H NMR spectrum: 400 MHz, Chloroform-d δ 7.83 (d, J = 8.0 Hz, 2H), 7.72 (s, 6H), 7.34 (s, 6H), 7.26 (s, 1H), 4.36 (d, J = 42.4 Hz, 8H), 3.29 (t, J = 6.9 Hz, 8H), 2.03 (s, 8H), 1.67 (t, J = 7.3 Hz, 8H), 1.22 (d, J = 7.5 Hz, 6H), 1.11 (d, J = 7.3 Hz, 9H), 0.64 (d, J = 8.1 Hz, 9H).

[0071] 5) Synthesis of IFE-Br2

[0072] Compound IFE-NO2 (0.317 g, 0.214 mmol) and iron powder (35 mg, 0.625 mmol) were added to a single-necked round-bottom flask, followed by the addition of 30 mL of glacial acetic acid. The mixture was stirred vigorously overnight at 80 °C. After cooling, the glacial acetic acid was evaporated under vacuum, and a saturated sodium bicarbonate solution was added until no more bubbles appeared. The mixture was then extracted twice with ethyl acetate, dried over anhydrous sodium sulfate, and the solvent was evaporated under vacuum. The crude product was subjected to silica gel column chromatography (petroleum ether: ethyl acetate = 1:1) to give 127 mg of an orange-yellow solid, with a yield of 41.6%.

[0073] The structural characterization data are as follows:

[0074] Mass spectrometry: [HR-MS (TOF)] m / z: 1426.1556

[0075] 1H NMR spectrum: 1H NMR (400MHz, DMSO-d6) δ 7.67 (d, J = 20.1 Hz, 6H), 7.44 (s, 1H), 7.33 (s, 4H), 5.89 (d, J = 38.4 Hz, 1H), 4.39 (d, J = 41.1 Hz, 8H), 3.32 (s, 233H), 2.50 (p, J = 1.9 Hz, 55H), 2.00 (d, J = 38.4 Hz, 11H), 1.58 (p, J = 7.0 Hz, 12H), 1.14 (d, J = 72.0 Hz, 44H), 0.81 (s, 5H).

[0076] 6) Synthesis of nitric oxide-responsive amphiphilic conjugated oligomer IFE-NH2

[0077] The obtained compound IFE-Br2 (20 mg, 0.014 mmol) was dissolved in trimethylamine (in tetrahydrofuran, 2 M), stirred at room temperature for 24 hours, and then the trimethylamine was evaporated under vacuum to obtain the nitric oxide-responsive amphiphilic conjugated oligomer IFE-NH2.

[0078] 7) Synthesis of IEG-N3

[0079] Compound IFE-Br2 (100 mg, 0.070 mmol) and sodium azide (46 mg, 0.7 mmol) were dissolved in DMF (10 mL) and heated at 70 °C for 3 hours. After the reaction was complete, a large amount of water was added and stirred until all the solids dissolved. The mixture was then extracted twice with ethyl acetate, dried over anhydrous sodium sulfate, and finally the solvent was evaporated under vacuum. The crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:1) to give 80 mg of an orange-yellow solid, with a yield of 89.5%.

[0080] The structural characterization data are as follows:

[0081] Mass spectrometry: HRMS (ESI) [M+Na+] m / z: 1297.5155

[0082] ¹H NMR spectrum: 400 MHz, DMSO-d⁶ δ 7.77 (d, J = 50.0 Hz, 4H), 7.44 (s, 1H), 7.31 (s, 2H), 5.90 (s, 1H), 4.44 (s, 2H), 4.34 (s, 2H), 3.27 (s, 8H), 3.18 (d, J = 6.9 Hz, 4H), 1.99 (d, J = 26.3 Hz, 5H), 1.31 (s, 7H), 1.23 (s, 8H), 1.12 (s, 5H), 1.04 (s, 11H), 0.87 (s, 7H), 0.56 (s, 4H).

[0083] 8) Synthesis of IEG-NH2, an amphiphilic conjugated oligomer responsive to nitric oxide

[0084] Tetrahydrofuran (2 mL), IEG-N3 compound (20 mg, 0.015 mmol), cuprous iodide (7.25 mg, 0.0375 mmol), and alkynyl-polyethylene glycol-methoxy (120 mg, 0.060 mmol) (Mn = 2000) were added to a reaction flask and stirred overnight at room temperature. The solution was then filtered through diatomaceous earth and the solvent was evaporated under vacuum to obtain the nitric oxide-responsive amphiphilic conjugated oligomer IEG-NH2.

[0085] Example 2: Preparation of nitric oxide-responsive amphiphilic conjugated oligomer self-assembled nanoparticles IFE-NH2-NPs

[0086] The nitric oxide-responsive amphiphilic conjugated oligomer IFE-NH2 was dissolved in 20 mL of ultrapure water and sonicated for 30 minutes to obtain an aqueous solution of nanoparticles. Aeration was then performed to remove residual organic solvents from the aqueous phase. Insoluble solid impurities were then removed by ultrafiltration using a 0.22 μm polyethersulfone (PES) membrane. The resulting aqueous solution of nanoparticles was then dialyzed in ultrapure water for 72 hours using a dialysis bag with a Mw = 1000 specification.

[0087] The product was freeze-dried in a vacuum freeze dryer to remove water, resulting in an orange-yellow solid product.

[0088] Example 3: Preparation of nitric oxide-responsive amphiphilic conjugated oligomer self-assembled nanoparticles IEG-NH2-NPs

[0089] The obtained nitric oxide-responsive amphiphilic conjugated oligomer IEG-NH2 was dissolved in 20 mL of ultrapure water and sonicated for 30 minutes to obtain an aqueous solution of nanoparticles. Aeration was performed to remove residual organic solvents from the aqueous phase. Insoluble solid impurities were then removed by ultrafiltration using a 0.22 μm polyethersulfone (PES) membrane. The resulting aqueous solution of nanoparticles was dialyzed in ultrapure water for 72 hours using a dialysis bag with a Mw of 10000. The solution was then filtered through a 220 nm membrane, and the resulting orange-yellow filtrate was stored at -4 °C.

[0090] Figure 2 To obtain the UV-Vis absorption spectrum of IFE-NH2-NPs nanoparticles.

[0091] Figure 3 To obtain the infrared spectrum of the nanoparticles IEG-NH2-NPs. The infrared spectrum shows that the compound IFE-Br2 has a wavelength of 2100 cm⁻¹. -1 There was no peak at 2100 cm⁻¹, while compound IEG-N3 showed a peak at 2100 cm⁻¹. -1 The appearance of the N3 peak indicates successful N3 attachment, with a peak at 2100 cm⁻¹ in the nanoparticles IEG-NH₂-NPs. -1 The disappearance of the peak indicates that IFE-NH2 was successfully synthesized.

[0092] Figure 4 The image shows a TEM image of IFE-NH2-NPs nanoparticles, which are spherical with uniform particle size.

[0093] Example 4: Preparation of IFE-NH2-NPs / NO nanoparticles by reaction with NO

[0094] Dissolve 20 mg of IFE-NH2-NPs nanoparticles in 10 mL of water, then add 1 mg of sodium nitrite and stir. Then add concentrated hydrochloric acid (6 M) drop by drop. It will be observed that the color changes rapidly from orange-yellow to dark blue. Then dialyze the mixture in ultrapure water for 72 hours using a dialysis bag with a specification of Mw=1000. The dark blue solid is obtained by freeze-drying.

[0095] Figure 5 The UV-Vis absorption spectra of IFE-NH2-NPs nanoparticles after reaction with NO are shown. (Comparison) Figure 2 and Figure 5 It can be seen that after the IFE-NH2-NPs nanoparticles react with NO, the absorption peak of the IFE-NH2-NPs nanoparticles red-shifts. Therefore, IFE-NH2-NPs nanoparticles can be used to detect the presence of NO in a system.

[0096] Figure 6 The fluorescence excitation spectra of IFE-NH2-NPs nanoparticles before and after the reaction with NO (650 nm excitation). Figure 6 It can be seen that the fluorescence intensity is enhanced after IFE-NH2-NPs nanoparticles react with NO.

[0097] Following the procedure in Example 4, IEG-IEG-N3 nanoparticles / NO were prepared, and the UV-Vis absorption spectra before and after the reaction were detected.

[0098] Figure 7 The images show the UV-Vis absorption spectra of compound IEG-N3 before and after its reaction with NO. After the reaction, the absorption peak of compound IEG-N3 red-shifts, indicating that it has reacted with NO. Compound IEG-N3 can be used to detect the presence of NO in a system.

[0099] Following the procedure in Example 4, IEG-NH2-NPs nanoparticles / NO were prepared, and the UV-Vis absorption spectra before and after the reaction were detected. Figure 8 As shown, after the IEG-NH2-NPs nanoparticles react with NO, the absorption peak of the IEG-NH2-NPs nanoparticles red-shifts. Therefore, IEG-NH2-NPs nanoparticles can be used to detect the presence of NO in a system.

[0100] Figure 9 Photothermal effect diagrams of IFE-NH2-NPs nanoparticles / NO obtained by the reaction of IFE-NH2-NPs with NO at different concentrations (0 mg / mL, 0.10 mg / mL, 0.15 mg / mL, 0.20 mg / mL, 0.30 mg / mL, 0.40 mg / mL).

[0101] The present invention has been described in detail above. Those skilled in the art will recognize that the invention can be practiced in a wide range of ways with equivalent parameters, concentrations, and conditions without departing from its spirit and scope, and without requiring unnecessary experiments. While specific embodiments have been provided, it should be understood that further modifications can be made to the invention. In summary, according to the principles of the invention, this application is intended to include any changes, uses, or improvements to the invention, including changes made using conventional techniques known in the art that depart from the scope disclosed herein.

Claims

1. An amphiphilic conjugated oligomer-based nanoparticle, which is self-assembled from the amphiphilic conjugated oligomers shown in Formula I. Formula I In Formula I, the Acceptor is the following group: Donor has the following groups: ； The shielding unit has the following functional groups: in, f and g are each independent integers from 1 to 10; R3 and R4 are each selected independently from: 、 R7 is H, C1-C6 alkyl; n=40-50; R8, R9, R 10 Each is independently selected from C1-C6 alkyl groups, and X is bromine.

2. The amphiphilic conjugated oligomer-based nanoparticles according to claim 1, characterized in that, The amphiphilic conjugated oligomers shown in Formula I are the following compounds: compound IFE-NH2 compound IEG-NH2 n= 40-50。 3. A method for preparing the amphiphilic conjugated oligomer-based nanoparticles according to claim 1 or 2, comprising the following steps: 1) dissolving the amphiphilic conjugated oligomer shown in Formula I in an organic solvent miscible with water, and then sonicating it; 2) The obtained mixture was added to ultrapure water, and nanoparticles were prepared by ultrasonic self-assembly. Inert gas was bubbled into the solution until all organic solvent evaporated to obtain an aqueous solution of nanoparticles. 3) The aqueous solution of the obtained nanoparticles was treated by dialysis to obtain amphiphilic conjugated oligomer-based nanoparticles.

4. The method according to claim 3, characterized in that, In step 1), the organic solvent is tetrahydrofuran, and the ultrasonic treatment time is 10-60 min; In step 2), the volume ratio of the mixture to ultrapure water is 1:2 to 1:10; The inert gas is argon; In step 3), the molecular weight cutoff of the dialysis bag is 1000D.

5. The application of the amphiphilic conjugated oligomer of formula I in claim 1 or the amphiphilic conjugated oligomer-based nanoparticles of claim 1 in the preparation of nitric oxide detection reagents.

6. A method for detecting the presence of nitric oxide in a system, comprising the following steps: contacting the amphiphilic conjugated oligomer-based nanoparticles of claim 1 with the system to be tested; if the ultraviolet absorption characteristics of the resulting system change, i.e., a new absorption peak appears at 500-700 nm, then the system is determined to contain nitric oxide; or irradiating the resulting system with near-infrared light in the wavelength range of 500-700 nm, if the system produces a photothermal effect or enhanced fluorescence, then the system is determined to contain nitric oxide; otherwise, the system does not contain nitric oxide. The test is not for the purpose of disease diagnosis or treatment.

Images