IR780 iodide-based lung targeting nano-carrier and application thereof

Abstract

The invention discloses a lung targeting nano-carrier based on IR780 iodide and a preparation method and application thereof, the lung targeting ability of IR780 is researched, a nano-system based on IR780 is successfully constructed, the nano-system is not interfered by large-range fluctuation of nanoparticle biological distribution influence factors in the traditional sense, nanoparticles effectively and accurately enter lung tissues, and the lung targeting nano-carrier has the advantages that the lung targeting ability of IR780 is improved; the off-target risk is effectively reduced, and the drug delivery rate is improved. The drug carrier can be used as a drug carrier for treating lung diseases, and can quickly go deep into tissues to quickly play a treatment role.

Description

Technical Field

[0001] The invention relates to the field of medicine, in particular to a lung-targeted nanocarrier based on IR780 iodide, and also to the application of the drug carrier. Background Art

[0002] Organ targeting technology has been increasingly valued in the field of biomaterials, especially in the field of lung-targeted nanotechnology. Through an overall survey of lung-targeted nanotechnology, only limited studies have reported the successful implementation of active targeting based on regulating nanomorphology, changing potential or post-synthetic modification of proteins or peptides, as well as passive targeting through respiratory administration. However, for large-scale production and product quality control, the morphological / potential differences between lung-targeted and non-targeted behaviors are too subtle to ensure interference and errors in synthesis; other methods are not only difficult to control costs, but also relatively complicated in the synthesis process. Based on protein or peptide targeting, the premise is to identify suitable tissue-specific candidate proteins, synthesize corresponding antibodies and then connect them to nanocarriers. The high cost, complex synthesis process, and purification problems caused by complexity have kept such methods in the laboratory verification stage for a long time. Importantly, those intravenously administered lung-targeted nanoparticles or LNPs have always faced the problems of pulmonary endothelial obstruction and inability to penetrate deeply, and respiratory administration is also limited by the air-blood barrier. IR780 iodide has been known for its excellent pan-tumor targeting since it was reported, and existing studies are all targeted at tumor models. The research and application of lung targeting behavior of IR780 iodide have not been reported before. Summary of the invention

[0003] One of the purposes of the present invention is to provide a lung-targeted nanosystem based on IR780 iodide; a second purpose of the present invention is to provide the use of the lung-targeted nanosystem based on IR780 iodide in the preparation of lung-targeted drug carriers; a third purpose of the present invention is to provide a lung-targeted drug containing the lung-targeted nanosystem; a fourth purpose of the present invention is to provide the use of the lung-targeted drug in the preparation of drugs for treating lung diseases.

[0004] In order to achieve the above object, the present invention provides the following technical solutions:

[0005] 1. A lung-targeted nanosystem based on IR780 iodide, wherein the lung-targeted nanocarrier is prepared by heating and dissolving a hyperbranched-linear-hyperbranched polymer, DSPC, Dlin-MC3-DMA, cholesterol, DMG-PEG2000, IR780 iodide and DMSO in anhydrous ethanol as an organic phase, using 0.01M pH=4.0MES buffer as an aqueous phase, and adding the organic phase to the aqueous phase with a ratio of 1:3 to 5, followed by heating and stirring, ice bathing, ultrafiltration, and dialysis with PBS buffer.

[0006] Preferably, the molar ratio of the hyperbranched-linear-hyperbranched polymer, DSPC, Dlin-MC3-DMA, cholesterol, DMG-PEG2000, IR780 iodide and DMSO is 1-10:5-15:0-50:5-15:1-10:5-30.

[0007] 2. Application of the IR780 iodide-based lung-targeted nanosystem in the preparation of lung-targeted drug carriers.

[0008] Preferably, in the present invention, the drug loaded in the lung-targeted drug carrier is pirfenidone.

[0009] 3. Lung-targeted drugs containing the lung-targeted nanosystem.

[0010] Preferably, the drug is pirfenidone.

[0011] 4. Use of the lung-targeted drug in the preparation of drugs for treating lung diseases.

[0012] Preferably, the lung disease is pulmonary fibrosis.

[0013] This study reported the lung targeting ability of IR780 for the first time and elaborated the mechanism behind its targeting. The L-HLNP@780 (Lung-specific Hybrid LNP@IR780) nanosystem was successfully constructed for the treatment of IPF (specific pulmonary fibrosis). The study of its lung targeting mechanism showed that the lung accumulation trend of L-HLNP@780 was almost unaffected by the large-scale fluctuations of the factors affecting the biodistribution of nanoparticles in the traditional sense (size and potential). The specific chemical structure of IR780 was the determining factor of its lung targeting ability, while other analogs with subtle structural changes showed completely different biodistributions. The composition of the nanoframe indirectly determined the release of the lung targeting ability of IR780. The release of lung targeting performance was achieved by changing the loading mode of IR780 from being encapsulated in the lipid bilayer to being loaded in the voids of the hyperbranched polymer on the outer surface of the nanoparticle, indicating that fully exposing the specific chemical structure of IR780 is crucial for releasing the instinctive lung targeting ability when loaded in the nanoframe.

[0014] The beneficial effects of the present invention are as follows: This study, for the first time, reveals the instinctive lung targeting properties of IR780 (L-HLNP@780 (Lung-specific Hybrid LNP@IR780)) with the help of an optimized hybrid LNP structure, and explores the mechanism behind this unique and efficient lung targeting. The nanoparticles constructed with the lung-specific aggregation properties determined by the structure of IR780 iodide itself can quickly, accurately and effectively penetrate the pulmonary vascular endothelial cells and infiltrate into deep tissues, effectively reducing the risk of off-target and improving the drug delivery rate. And the lung targeting strategy based on this does not require post-synthetic modification of proteins or other targets, so with the discovery of this small molecule, the technical process of achieving lung-targeted biodistribution has been significantly simplified and improved. Based on this, the application of lung-targeted nanocarriers based on IR-780 is definitely not limited to the treatment of IPF, but a wider range of fields, such as lung infections, and ARDS, because we observed that L-HLNP@780 passes through the basement membrane in a short time of 0.5h, and can quickly penetrate into the tissue to quickly exert a therapeutic effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] In order to make the purpose, technical solution and beneficial effects of the present invention clearer, the present invention provides the following drawings for illustration:

[0016] Figure 1 The preparation process and characterization of L-HLNP@780, the five-pointed star represents IR780 (A: concentration / fluorescence intensity calibrator of IR780; B: loading rate of IR780 and pirfenidone; C: concentration of pirfenidone detected by mass spectrometry liquid chromatography; D: TEM observation of the structures of L-HLNP@780(S4-1st), LNP@780(S-LNP(-Den)), and L-HLNP / P@780(Sp-1st); E: cytotoxicity detection of nanoparticles);

[0017] Figure 2 To verify the lung-specific aggregation of L-HLNP@780 nanoparticles (A: fluorescence image; B: in vivo distribution of nanoparticles);

[0018] Figure 3 Verification of the lung targeting of L-HLNP@780 nanoparticles (A: chemical structure; B: in vivo imaging results);

[0019] Figure 4 The effects of Den and Dlin-MC3-DMA (MC3) on lung targeting (A: fluorescence imaging of each nanoparticle; B: statistical results);

[0020] Figure 5Effects of different dendrite-linear-dendrite block copolymers on lung targeting (A: different dendrite-linear-dendrite block copolymer structures; B: 24-hour fluorescence images; C: lung / liver fluorescence ratio; D: particle size);

[0021] Figure 6 For the treatment effect of IPF.

[0022] Figure 7 The results are shown in electron microscope observation of lung tissue after fixation with glutaraldehyde. DETAILED DESCRIPTION

[0023] The present invention is further described below in conjunction with the accompanying drawings and specific embodiments so that those skilled in the art can better understand the present invention and implement it, but the embodiments are not intended to limit the present invention.

[0024] The nanosystem used to load IR780 iodide in this experiment is a composite liposome, which is composed of hyperbranched-linear-hyperbranched polymer (bis-MPA hyperbranched PEG10k-OH, pseudo G3, referred to as Den), DSPC, Dlin-MC3-DMA (MC3), cholestrol, DMG-PEG2000, IR780 iodide, DMSO solution heated and dissolved in anhydrous ethanol as the organic phase (molar ratio 1-10:5-15:0-50:5-15:1-10:5-30), 0.01M pH=4.0MES buffer as the aqueous phase, organic phase: aqueous phase 1:3-5, the organic phase is added dropwise under heating and stirring, followed by ice bath, ultrafiltration, and PBS buffer dialyzation, and stored at 4 degrees.

[0025] This embodiment is the best embodiment of the present invention. In which the analogs of IR780, IR676, IR775, and IR783, are used in L-HLNP@780 ( Figure 1Different types of nanoparticles were synthesized under the same framework of (A, the name is replaced by S4-1st). The specific steps are as follows: Bis-MPA hyperbranched PEG10k-OH (pseudo G3), MC3, DSPC (distearoylphosphatidylcholine), cholesterol, and DMG-PEG 2000 were dissolved in ethanol at a certain molar ratio (5:45:10:10:10:5), mixed with IR780 (dissolved in DMSO), heated to 50°C, 3 volumes of MES buffer (pH = 4.0) were magnetically stirred in the ethanol mixture for 2 minutes to form L-HLNP@780, ice bath, ultrafiltration, and PBS (pH = 7.3) dialyzed. The final product was stored at 4°C. The control group L-HLNP@676 / 775 / 783 (i.e., S-676, S-775, S-783) and the drug-loaded group L-HLNP / P@780 (Lung-specific Hybrid Pirfenidone-loaded LNP, i.e., Sp-st, pirfenidone was added to the organic phase during the preparation process) were synthesized according to the same steps.

[0026] The characterization results of L-HLNP@780 are shown in Figure 1 The results show that the lipophilic IR780 is first encapsulated in the voids of Den, namely Den@780, and then forms the outer surface of L-HLNP@780 due to the strong hydrophilicity conferred by the PEG core and 16 OH-terminal groups, covering the lipid layer, as shown in transmission electron microscopy. Figure 1 As shown in E. Compared with the regular thin multilayers of LNP without Den formation, L-HLNP@780 has a thicker shell structure, which appears as an electron transparent area due to the weak electron scattering of Den on the surface. In addition to observing L-HLNP@780, negative staining transmission electron microscopy also detected nanoparticles in the drug-loaded state, showing a similar thick shell structure. UV spectrophotometry and LC-MS techniques were used to detect the loading rates of IR780 and pirfenidone, respectively. Figure 1 As shown in B, C, and D, the regression equation of IR780 is Y=69.22*X+1.894, R2=0.9992 (Y=absorbance value at 780nm, X=concentration of IR780), from which the drug loading rate of IR780 is calculated to be 95.58

[0027] ±5.094%; the regression equation of pirfenidone is y=280433*x-316802, R2=0.9994 (y=peak area, x=pirfenidone concentration), from which the drug loading rate of pirfenidone is calculated to be 28.38±15.170%. In addition, the cytotoxicity of L-HLNP@780 in LLC cell line was detected by CCK8 method. The results showed that when the concentration of nanoparticles reached a high level of 0.5960mg / ml, the nanoparticles did not show obvious cytotoxicity, thus ensuring the biosafe application in subsequent in vitro / in vivo experiments ( Figure 1 , F).

[0028] Example 1: Verification of lung targeting of L-HLNP@780 nanoparticles

[0029] 200 μl (1 mg / ml) L-HLNP@780 nanoparticles were injected into the tail vein of healthy 8-week-old C57 BL / 6N male mice. The in vivo distribution of nanoparticles (ex / em=740 / 790 nm) was detected at different time points using the Perkin Elmer IVIS Lumina small animal in vivo imaging instrument. The results are shown in Figure 2. Figure 2 As shown. Similarly, the organs (liver, spleen, and lung) of mice injected with nanoparticles were collected at different time points, sliced, and observed under a laser confocal microscope. The results showed that the nanoparticles showed the characteristics of rapid penetration from blood vessels to deep lung tissue in the lungs, while in the liver and spleen, they showed transient short-term vascular retention, and the fluorescence disappeared quickly over time.

[0030] Example 2. Correlation between specific lung aggregation and the chemical structure of IR780

[0031] Verify that the specific aggregation of L-HLNP@780 in the lungs is related to the chemical structure of IR780. The specific steps are as follows:

[0032] From the perspective of nanoparticles, the key role was decomposed into the remaining possible parts, including IR780 alone, the remaining parts except IR780, and the combination of the two parts. The chemical structure of IR780 includes an unsaturated six-ring with an indole-containing side chain on each side. At the same time, three analogs IR676, IR775, and IR783 were selected as substitutes for IR780 for simultaneous experiments. The chemical structures of IR676, IR775, IR783, and IR780 are shown in Figure 1. Figure 3 As shown in A, according to the structural analysis, it can be seen that the difference between IR676 and IR780 is that IR676 does not have an unsaturated six-ring and the excitation / emission wavelength is shorter; the similarity is that IR676 has the same side chain - indole and I -IR775 and IR783 have the same unsaturated six rings and similar excitation / emission wavelengths, but the side chains of indole are changed from n-propyl to methyl and sulfobutyl ether, and I- to Cl- and Na-, respectively. + The four compounds were loaded into the same nanosystem in the same way as IR780, namely S4-676, S4-775, and S4-783.

[0033] Twenty-seven healthy 8-week-old male C57 BL / 6N mice were randomly divided into three groups and injected intravenously with 200 μl (1 mg / ml) nanoparticles. The biodistribution of each nanoparticle was detected by in vivo fluorescence imaging (ex / em=740 / 790nm) at 24h, 48h, and 72h after tail vein injection of each nanoparticle (Ex / Em=640nm / 680nm for IR676, Ex / Em=740nm / 790nm for IR775, IR780, and IR783). The results are shown in Figure 2. Figure 3 As shown in B, the rapid accumulation and retention behavior of IR780 in the lungs (L-HLNP@780). While S4-676 was mainly trapped in the liver and gastrointestinal tract within the first 24 hours, only a small portion of S4-676 could be detected in the gastric area when the time was extended to 72 hours. In the first 24 hours, S4-775 basically accumulated in the liver, and a small portion of the nanoparticles were dispersed in the lungs, kidneys, and spleen. The fluorescence disappeared rapidly within 48 hours, and only a weak fluorescence was detected in the liver, which disappeared within 72 hours. Throughout the detection process, the biodistribution of S4-783 showed a trend of accumulation in the spleen. Although the total fluorescence intensity of each organ was still the strongest in the liver, the fluorescence intensity per tissue weight (gram) was the highest in the spleen. The above results indicate that IR780 can target the lungs. It is possible that the chemical structure of IR780 is crucial for L-HLNP@780 to target the lungs, and changes in the chemical structure of each part of IR780 will lead to the loss of lung-specific accumulation and retention.

[0034] Example 3: Study on the specific aggregation mechanism of L-HLNP@780 in the lungs

[0035] To verify whether the specific aggregation of L-HLNP@780 in the lungs is related to the exposure of the chemical structure of IR780 on the surface of the nanoparticles, the following steps were performed:

[0036] A. The lung targeting ability of IR780-LNP is only released when Den (bis-MPA hyperbranched PEG10k-OH, pseudo-G3) is added to the nanosystem. According to previously reported studies, when IR780 is loaded into nanoparticles composed of these basic components (phospholipids, cholesterol, PEGylated lipids), almost only tumor-specific accumulation is observed, rather than lung accumulation. Tumors are widely considered to be the disease model of choice, and the intrinsic lung targeting ability of IR780 has not been discovered before this study. Based on this situation, Den and Dlin-MC3-DMA (MC3) in L-HLNP@780 stand out as two potential components that may play a key role. Therefore, we synthesized four combinations of Den+ / MC3+, Den- / MC3+, Den+ / MC3-, and IR780 solution (pure IR780) and verified them in vivo. The biodistribution of each nanoparticle was observed by in vivo fluorescence imaging at 6 hours and 48 hours after injection, respectively. From Figure 4 As can be seen from Figure A, pure IR780 accumulates rapidly in the lungs, has high specificity (6h), has a long retention time, and a lung / liver fluorescence ratio of nearly 30; the Den+ / MC3+ group with the same composition as L-HLNP@780 exhibits similar lung targeting behavior as pure IR780, with a lung / liver fluorescence ratio of up to 25; the Den- / MC3+ group exhibits completely different biodistribution characteristics, with fluorescence distribution in the liver, lungs, spleen, kidneys, and gastrointestinal tract being relatively even within 6 hours, and mainly accumulated in the liver and spleen within 48 hours, with a small amount retained in the lungs, kidneys, and gastrointestinal tract. The lung / liver fluorescence ratio was as low as 5 in the GI tract. There was a statistically significant difference in the lung / liver fluorescence ratio between the Den+ / MC3+ group and the Den- / MC3+ group (p=0.0007). The results of the Den+ / MC3- group and the Den+ / MC3+ group were similar, and both were specifically concentrated in the lungs within 48 hours, with a lung / liver fluorescence ratio as high as 23, which was not significantly different from the Den+ / MC3- group (p=0.06527). However, the fluorescence of the Den+ / MC3- group was relatively evenly dispersed in the liver, lungs, spleen, kidneys, and gastrointestinal tract within 6 hours. Figure 4 Judging from the obvious error bars of the Den+ / MC3- group in B, its lung targeting ability is in an unstable state. Considering that MC3 is an ionizable cationic lipid that can help assemble other negatively charged components during the synthesis of nanoparticles, it is speculated that the lack of MC3 may lead to unstable and delayed lung accumulation by affecting the stability of nanoparticles. But overall, the lung targeting ability of IR780 in the Den+ / MC3- group was restored. The fluorescence of the Den- / MC3- group was dispersed in various organs throughout the detection process, and the lung / liver fluorescence ratio was as low as 5. The difference between the Den- / MC3- group and the Den+ / MC3+ group was statistically significant (p<0.0001).

[0037] In summary, we can reasonably infer that the release of IR780's intrinsic lung targeting ability is related to Den.

[0038] B. The loading method of IR780 can release its lung targeting ability. The dendrimers used in the study, or specifically Den (short for dendron-linear-dendron block copolymer hybrid), usually load small molecules by achieving electrostatic adsorption through terminal functional groups and the spatial structure formed by repeating branch units (i.e., void space). Considering that the terminal functional group -OH leads to its electrical neutrality, it can be inferred that the Den used in this study is loaded with IR780 through void space. This paper selects Den with the same number of -OH end groups and the same branch units but different core structures to replace the original Den in order to exclude chemical structure factors. The chemical structures of the two Den are shown in Figure 5 As shown in A. The mice were divided into two groups and treated with S4-new Den and S4-1st respectively. Fluorescence images were taken 24 hours after tail vein injection. Figure 5 As shown in Figure B, both nanoparticles have high specificity for the lung. Figure 5 As can be seen from the data in C, the lung / liver fluorescence ratios of S4-new Den and S4-1st reached 24 and 23, respectively. There was no statistically significant difference between the two groups (p = 0.8095). Therefore, the lung targeting ability of IR780 can be masked or released according to the loading method. More specifically, when the nanocarrier exposes the structure of IR780 on the outer surface, the nanosystem will accumulate specifically in the lung. So far, the chemical structure and loading method of IR780 have been confirmed to be two key factors in the lung targeting phenomenon.

[0039] The test results of this implementation are the same as those of Example 1.

[0040] Example 4: Effect of particle size on lung targeting activity of L-HLNP@78

[0041] To verify whether Zeta potential is an influencing factor of lung targeting activity in L-HLNP@780, the specific steps are as follows:

[0042] In the field of nanomaterials, it is generally believed that there is a close relationship between the surface properties of nanocarriers and their biodistribution. Although there is no definite conclusion to explain this correlation, published studies and reviews believe that nanoparticles of different sizes have different possibilities of being captured mainly by the reticuloendothelial system (RES) present in the liver, lungs, spleen, brain, kidneys, gastrointestinal tract, etc. The liver and spleen are considered to be two powerful physiological barriers to block and capture these foreign bodies. In 2020, researchers developed a SORT system, claiming that these specific permanently negatively / positively charged lipids can regulate the accumulation of nanoparticles in the liver, lungs, or spleen by changing the potential of the nanosystem. Although the clear mechanism behind the regulation has not yet been clarified, the potential is indeed a crucial variable. In this study, one of the SORT molecules (DSPA, a permanently negatively charged lipid that has previously been shown to cause spleen accumulation) was first selected to be added to L-HLNP@780, namely S4-DSPA. According to Figure 5 In vivo fluorescence imaging results of B and Figure 5 The statistics in C show that the neutral S4-1 became negatively charged when DSPA was added, but both S4-1 and S4-DSPA showed rapid and effective lung targeting behavior within 12 hours after tail vein injection. There was no statistically significant difference in the lung / liver fluorescence ratio between S4-1 and S4-DSPA (p=0.1191). Based on these findings, a permanently positively charged lipid, namely DDAB, was selected to further exclude potential factors; in order to exclude the interference of the chemical structure of DSPA, we selected four similar permanently negatively charged lipids, DSPA, DMPA, DOPA and DDAB, to be added to L-HLNP@780. Figure 5 As shown in Figures B and C, the four nanoparticles S4-DSPA, S4-DMPA, S4-DOPA, and S4-DDAB all showed extraordinary lung targeting ability, and there was no statistically significant difference in the lung / liver fluorescence ratio between s4-1 and the other four nanoparticles (p = 0.1191, 0.0823, 0.1741, and 0.4552, respectively). At the same time, the hydrated particle size of various nanoparticles was detected. Figure 5As can be seen in D, S4-1 has the smallest size, and the sizes of the others are between 200nm and 300nm. The size difference between S4-1 and other groups is statistically significant (p = 0.0045, 0.0030, 0.0005, and 0.0120, respectively). The five nanoparticles used in the experiment all showed similar lung targeting ability, but the corresponding zeta potential and size were significantly different, indicating that zeta potential is not an influencing factor of the lung targeting activity of L-HLNP@780; at the same time, the current data results show that particle size is not an influencing factor, but the conclusion needs more rigorous verification. Fluorescence imaging was performed on nude mice to track the targeting of S4-DSPA (S4-2nd) to the lungs for 0.5h to 336h. Similar to the case of L-HLNP@780 (S4-1st), a fluorescence peak appeared in the lungs 48h after injection and gradually decreased.

[0043] Example 5: Therapeutic effect of the pirfenidone-loaded nanosystem L-HLNP / P@780 on a specific pulmonary fibrosis mouse model

[0044] The synthesis steps of drug-loaded nanoparticles L-HLNP / P@780 are the same as above, wherein pirfenidone is dissolved in anhydrous ethanol and added at a dosage of 5 mg / sample. The IPF mouse model was constructed by tracheal instillation of bleomycin (5 mg / kg). Treatment began on the twelfth day after modeling, using tail vein injection (one dose per day for four consecutive days, 1 mg / ml, 300 μl / time). The treatment effect was tested on the thirtieth day after modeling, and the fibrosis of mouse lung tissue was verified by HE staining, Sirius red staining, and α-SMA immunohistochemistry. The results are as follows: Figure 6 shown.

[0045] Example 6: Continuous observation of nanoparticles entering lung tissue under high-resolution electron microscopy

[0046] C57 BL / 6N male mice injected with L-HLNP@780 via the tail vein were killed at different time points (0.5h, 1h, 2h, 4h, 24h, 48h, 120h), and then the lung tissues were fixed with glutaraldehyde and observed under an electron microscope. The results are shown in Figure 2. Figure 7 As shown, nanoparticles were observed to penetrate the pulmonary vascular endothelial cells 0.5 hours after injection and then enter the deep lung tissue, reaching a peak at 48 hours and being gradually metabolized after 120 hours.

[0047] The above-described embodiments are only preferred embodiments for fully illustrating the present invention, and the protection scope of the present invention is not limited thereto. Equivalent substitutions or changes made by those skilled in the art based on the present invention are within the protection scope of the present invention. The protection scope of the present invention shall be subject to the claims.

Claims

1. A lung-targeted nanosystem based on IR780 iodide, characterized in that: The lung-targeted nanocarrier is prepared by heating and dissolving a hyperbranched-linear-hyperbranched polymer, DSPC, Dlin-MC3-DMA, cholesterol, DMG-PEG2000, IR780 iodide and DMSO in anhydrous ethanol as an organic phase, using 0.01M pH=4.0MES buffer as an aqueous phase, and adding the organic phase to the aqueous phase with a ratio of 1:3 to 5 under heating and stirring, followed by an ice bath, ultrafiltration, and dialysis with PBS buffer.

2. The lung-targeted nanosystem based on IR780 iodide according to claim 1, characterized in that: The molar ratio of the hyperbranched-linear-hyperbranched polymer, DSPC, Dlin-MC3-DMA, cholesterol, DMG-PEG2000, IR780 iodide and DMSO is 1-10:5-15:0-50:5-15:1-10:5-30.

3. Use of the lung-targeted nanosystem based on IR780 iodide according to claim 1 in the preparation of lung-targeted drug carriers.

4. The use according to claim 3, characterized in that: The drug loaded in the lung-targeted drug carrier is pirfenidone.

5. A lung-targeted drug containing the lung-targeted nanosystem according to claim 1 or 2.

6. The lung-targeted drug according to claim 5, characterized in that: The drug is pirfenidone.

7. Use of the lung-targeted drug according to claim 5 in the preparation of drugs for treating lung diseases.

8. The use according to claim 7, characterized in that: The lung disease is pulmonary fibrosis.

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