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WO2024152405A1 - Sonde fluorescente de type à ancrage d'acide nucléique intégrée au diagnostic et au traitement, son procédé de préparation et son utilisation - Google Patents

Sonde fluorescente de type à ancrage d'acide nucléique intégrée au diagnostic et au traitement, son procédé de préparation et son utilisation Download PDF

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WO2024152405A1
WO2024152405A1 PCT/CN2023/077769 CN2023077769W WO2024152405A1 WO 2024152405 A1 WO2024152405 A1 WO 2024152405A1 CN 2023077769 W CN2023077769 W CN 2023077769W WO 2024152405 A1 WO2024152405 A1 WO 2024152405A1
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cri
nucleic acid
probe
fluorescent probe
anchored
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Chinese (zh)
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史海斌
冯雅丽
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Suzhou University
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Suzhou University
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/64—Cyclic peptides containing only normal peptide links
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
    • C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials

Definitions

  • molecular probes play an important role in the precise diagnosis and treatment of cancer. Although a large number of molecular imaging probes have been developed for cancer imaging and treatment, they often fail to achieve the purpose of precise diagnosis and treatment due to poor tumor specificity and the possibility of damaging normal tissues.
  • TME tumor microenvironment
  • endogenous substances such as overexpressed enzymes, acidic pH, high-reducing glutathione, and hypoxia
  • activatable diagnostic and therapeutic strategies are only triggered by a single factor, which is usually not enough to effectively avoid normal cells and accurately ablate cancer cells, resulting in potential false-positive or false-negative diagnostic and therapeutic results.
  • light has been proven to be an attractive tool for precise activation therapy with spatiotemporal controllability without the need for physical contact.
  • the present invention constructs a new type of anchored molecular probe, which utilizes its advantages of cross-linking groups, good biocompatibility, active targeting integrin and near-infrared emission to perform long-term in vivo fluorescence, photoacoustic imaging and tumor treatment.
  • a novel integrated diagnosis and treatment nucleic acid anchored fluorescent probe having the following chemical structure:
  • the preparation method of the above-mentioned integrated diagnosis and treatment nucleic acid anchored fluorescent probe comprises the following steps:
  • the preparation method of the above-mentioned integrated diagnosis and treatment nucleic acid anchored fluorescent probe comprises the following steps:
  • the present invention discloses a red light-mediated probe-anchored cell method, comprising the following steps: co-incubating the above-mentioned integrated diagnosis and treatment nucleic acid-anchored fluorescent probe and cells to achieve probe-anchored cells; wherein the co-incubation is carried out under light in a culture medium (such as 1640 culture medium).
  • a culture medium such as 1640 culture medium
  • the cyclic peptide cRGD reacts with the dye IR780 in an organic solvent to obtain the compound CRI; the compound CRI reacts with the activated 3-(2-furan)propionic acid and N,N-diisopropylethylamine (DIPEA) in an organic solvent to obtain the anchored molecular probe ⁇ -CRI; the molar ratio of the cyclic peptide cRGD to the dye IR780 is 1: (1 to 1.2); preferably, the molar ratio of the compound CRI to 3-(2-furan)propionic acid is 1: (1 to 1.5).
  • DIPEA N,N-diisopropylethylamine
  • the present invention discloses the application of the above-mentioned integrated diagnosis and treatment nucleic acid anchored fluorescent probe in fluorescence imaging and photoacoustic imaging; or the application of the above-mentioned integrated diagnosis and treatment nucleic acid anchored fluorescent probe in the preparation of fluorescence imaging agents and photoacoustic imaging agents; or the application of the above-mentioned integrated diagnosis and treatment nucleic acid anchored fluorescent probe in increasing the retention time of the probe in tumor tissue or inhibiting tumors, or the application of the above-mentioned integrated diagnosis and treatment nucleic acid anchored fluorescent probe in the preparation of reagents that increase the retention time of the probe in tumor tissue or inhibit tumors; or the application of the above-mentioned integrated diagnosis and treatment nucleic acid anchored fluorescent probe in the preparation of reagents that react with cytoplasm.
  • the present invention has the following advantages compared with the prior art:
  • the present invention designs and synthesizes a new type of anchored molecular probe ⁇ -CRI, which can perform long-term in vivo fluorescence and photoacoustic imaging under the red light-mediated generation of singlet oxygen;
  • the target probe in the present invention can undergo a cross-linking reaction with the intracellular RNA under the red light-mediated generation of singlet oxygen, thereby prolonging the retention time of the probe molecule in the cell;
  • the target probe of the present invention has a good ability to promote tumor cell apoptosis by causing mitochondrial damage after RNA cross-linking in tumor cells;
  • the target probe of the present invention has the ability to inhibit tumor growth in tumor-bearing mice after undergoing cross-linking reaction in vivo.
  • FIG1 is a schematic diagram of the synthesis of the integrated diagnosis and treatment nucleic acid-anchored fluorescent probe in Example 1.
  • Figure 2 shows (a) the chemical structures of the experimental group probe ⁇ -CRI and the control group probe CRI in Example 2, (b) the ultraviolet absorption and fluorescence emission images of the probe ⁇ -CRI and probe CRI in aqueous solution, and (c) the evaluation of the singlet oxygen generation ability of the probe ⁇ -CRI and probe CRI.
  • Figure 3 shows (a) the gel electrophoresis of the cross-linking reaction between RNA and ⁇ -CRI, (b) the confocal images and colocalization rates of 4T1 cells incubated with ⁇ -CRI in the experimental group and probe CRI in the control group for 6 hours and then incubated with RNA Select (c, d), and (e, f) the fluorescence and quantitative images of the total cellular RNA extracted by the RNA total kit.
  • Figure 4 shows (a) the experimental group probe ⁇ -CRI and the control group probe CRI were incubated with 4T1 cells for 6 hours and then illuminated, and then the confocal images were used to observe the changes in the retention of the probes in the cells and the quantification of the fluorescence intensity (b), (c) the experimental group probe ⁇ -CRI and the control group probe CRI were injected into the tail vein, and illumination was given four hours later to observe the changes in the retention of the probes in the tumor tissue and the quantification of the fluorescence intensity (d); under the same experimental conditions, the experimental group probe ⁇ -CRI and the control group probe CRI showed the changes in the photoacoustic signal in the tumor (e) and the quantification of the photoacoustic intensity (f).
  • Figure 5 shows (a) the changes in cytotoxicity of the experimental group probe ⁇ -CRI and the control group probe CRI after incubation with 4T1 cells for 12 hours, (b) the changes in cytotoxicity of the experimental group probe ⁇ -CRI and the control group probe CRI after incubation with 4T1 cells for 12 hours and then irradiated with light (808 nm 0.5w/ cm2 3 min), (c) the changes in cell apoptosis were observed using live-dead and cell bright field respectively after incubation with 4T1 cells for 12 hours and then irradiated with light (808 nm 0.5w/ cm2 3 min); (d) the ability to inhibit the proliferation and migration of tumor cells.
  • Figure 6 shows (a) the 15-day continuous change process of tumor inhibition by the experimental group probe ⁇ -CRI, the control group probe CRI, and the blank group PBS, (b) the comparison of the size of the mouse back tumor on the 15th day, (c) the size of the in vitro tumor on the 15th day, (d) the tumor inhibition curve, (e) the survival cycle curve, and (f) the changes of Tunel and H&E were examined by immunofluorescence and immunohistochemistry respectively 48 hours after treatment.
  • FIG. 7 is a schematic diagram showing the operation of the probe of the present invention.
  • the probe of the present invention is an RNA-reactive fluorescent probe.
  • the probe can react with intracellular RNA under red light irradiation, prolong the retention time of the probe in tumor cells, and achieve long-window tumor imaging; more importantly, this cross-linking reaction causes mitochondrial damage, leading to severe tumor cell apoptosis, thereby inhibiting tumor growth.
  • the steps of synthesizing the integrated diagnosis and treatment nucleic acid anchored fluorescent probe ⁇ -CRI of the present invention are as follows: the cyclic peptide cRGD reacts with the dye IR780 to obtain the compound CRI; the compound CRI reacts with the activated 3-(2-furan) propionic acid to obtain the integrated diagnosis and treatment nucleic acid anchored fluorescent probe ⁇ -CRI.
  • CRI is used as a control group probe.
  • aqueous solutions of the anchored molecular probe ⁇ -CRI and the control group probe CRI were incubated with tumor cells for 48 hours and then the apoptosis of tumor cells was observed.
  • the method for in vivo tumor inhibition experiment using the novel anchored molecular probe includes the following steps: first, the aqueous solution of the probe ⁇ -CRI is injected into the body of tumor-bearing mice through the tail vein, and after 4 hours, the tumor inhibition is continuously observed and recorded by illumination. The probe ⁇ -CRI is replaced with the control group CRI for a control experiment.
  • In vivo fluorescence imaging The probe was injected into the body of a tumor-bearing (4T1 mouse breast cancer) BALB/c female mouse via tail vein injection. The mouse was then placed in the small animal in vivo optical imaging system/IVIS Spectrum (PerkinElmer). Four hours later, the tumor site was illuminated (0.5 W/ cm2 for 3 min) and the imaging effect was observed in real time. Finally, the fluorescence intensity of the tumor site at different time points was calculated using in vivo imaging analysis software.
  • Tumor inhibition experiment 4T1 cells (2 ⁇ 10 6 cells) were implanted into the left and right backs of female BALB/c mice. When the tumor size reached 50-70 mm 3 , f -CRI probe (100 ⁇ M, 200 ⁇ L) or control CRI probe (100 ⁇ M, 200 ⁇ L) was injected intravenously. Four hours after injection, the right tumor was irradiated with 808 nm laser (0.5 W/cm 2 ) for 3 minutes.
  • control group CRI cRGD (33.5 mg, 0.06 mmol), IR780 (13.3 mg, 0.02 mmol) were dissolved in DMF (2 mL), stirred at room temperature for 12 h, the crude product was collected, and the control group product was separated by preparative HPLC.
  • MALDI-MS Calcd. For C 57 H 80 N 11 O 7 S + [M+] 1062.596, found: 1062.866. Yield 63% (15 mg).
  • control group probe CRI and the experimental group probe ⁇ -CRI prepared in Example 1 were diluted with ultrapure water to a concentration of 10 ⁇ M (completely soluble), and their UV-visible near-infrared spectra and fluorescence spectra were measured using a UV-visible near-infrared spectrophotometer and a fluorescence spectrophotometer.
  • Figure 2 (a) and Figure 2 (b) the results show that the maximum absorption of the probes CRI and ⁇ -CRI is at 788 nm, and the maximum emission is at 816 nm.
  • the control group probe CRI and the experimental group probe ⁇ -CRI produced more singlet oxygen as the illumination time increased.
  • CRI and ⁇ -CRI were diluted with ultrapure water to a concentration of 10 ⁇ M, respectively, and 30 ⁇ M of custom sequence RNA (5 ⁇ -ACAUCGGGAUAGCGAAGUUGAGAGAGGGAG-3 ⁇ ) was added. After mixing, the mixture was shaken at 4°C and exposed to 808 nm light (0.5 W/cm 2 , 1 min) or not exposed to light (protected from light). The reaction solution was directly separated by RNA non-denaturing gel electrophoresis, as shown in Figure 3a. It can be found that ⁇ -CRI can obviously label RNA after adding RNA and irradiating it, while other groups did not have obvious red fluorescence of IR780.
  • CRI and ⁇ -CRI were added to the culture medium (HyClone 1640 high-glucose liquid culture medium containing 10% FBS) at a concentration of 10 ⁇ M, and then added to 4T1 cells (2 ⁇ 10 5 ) and cultured for 6 h. They were then exposed to 808 nm light (0.5 W/cm 2 , 3 minutes) or not exposed to light (protected from light), and then stained with the singlet oxygen fluorescent probe DCFH-DA. As shown in Figure 3b, the CRI and ⁇ -CRI illumination groups both showed obvious green fluorescence, while the other groups did not.
  • CRI and ⁇ -CRI were added to the culture medium (HyClone 1640 high-glucose liquid culture medium containing 10% FBS) at a concentration of 10 ⁇ M, and then added to 4T1 cells (2 ⁇ 10 5 ) for 6 h. They were then irradiated with 808 nm light (0.5 W/cm 2 , 3 minutes) or not irradiated (protected from light), and then stained with the commercial RNA dye SYTO RNASelect green fluorescent cell stain (Thermo Fisher), as shown in Figures 3c and 3d.
  • the colocalization rate of the experimental group ( ⁇ -CRI+808 nm) was greater than that of the other groups, and also higher than that of the existing probes C 75 H 99 N 13 O 17 S 2 ( ⁇ -CR, about 0.63) and C 72 H 90 N 15 O 16 P ( ⁇ -RCP, about 0.62).
  • the total RNA in the cells was then extracted by Trizol, and fluorescence quantification revealed that the experimental group ( ⁇ -CRI+808 nm) had a significantly higher colocalization rate than the other groups.
  • the fluorescence intensity of the experimental group ( ⁇ -CRI+808 nm) was much greater than that of the other groups, as shown in Figure 3e.
  • cytoplasmic RNA was extracted using the Cytoplasm & Nuclear Total Extraction Kit and analyzed by RNA non-denaturing gel. It was found that the experimental group ( ⁇ -CRI+808 nm) had obvious red fluorescence, while the other groups did not produce obvious fluorescence, as shown in Figure 3f.
  • CRI and ⁇ -CRI were added to the culture medium (HyClone 1640 high-glucose liquid culture medium containing 10% FBS) at a concentration of 10 ⁇ M. After being added to 4T1 cells and cultured for 6 hours, the materials were observed to be retained in the cells with or without irradiation (protected from light) at 808 nm. It was found that the retention experiment of the experimental group ( ⁇ -CRI +808 nm) was much greater than that of the other groups, as shown in Figures 4a and 4b. Subsequently, the retention experiment of the probe in mouse tumors was investigated.
  • the culture medium HyClone 1640 high-glucose liquid culture medium containing 10% FBS
  • CRI and ⁇ -CRI were diluted with PBS to a concentration of 100 ⁇ M in 200 mL, and CRI or ⁇ -CRI was injected into the tail vein. After 4 hours, 808 nm light was irradiated (0.5 W/cm 2 , 3 minutes) or without irradiation (protected from light). The metabolism of the probe in the tumor at each time point was observed by IVIS, as shown in Figures 4c and 4d. It was found that the experimental group ( ⁇ -CRI +808 nm) The retention time of the 247nm group in the body was much longer than that of the other groups.
  • CRI and ⁇ -CRI were diluted with PBS to a concentration of 100 ⁇ 200 ⁇ L, and then CRI or ⁇ -CRI was injected into the tail vein. After 4 hours, 808 nm light (0.5 W/ cm2 , 3 minutes) or no light (protected from light) was applied. At the same time, the photoacoustic imaging system was used to investigate the changes in the photoacoustic signal at each time point. The photoacoustic imaging data were reconstructed and analyzed using MSOT InSight/inVision analysis software. It was found that compared with other groups, the experimental group ( ⁇ -CRI +808 nm) had a long-lasting photoacoustic signal, as shown in Figures 4e and 4f.
  • CRI and ⁇ -CRI were diluted to 80, 40, 20, 10, 1, and 0.1 ⁇ M in culture medium (RPMI1640 culture medium containing 10% FBS), and added to 4T1 cells for 12 h. It was found that CRI and ⁇ -CRI had no obvious toxicity, as shown in Figure 5a. Under the same experimental conditions, after 808 nm light (0.5 W/cm 2 , 3 minutes) was given and cultured for 48 h, it was found that the experimental group ( ⁇ -CRI +808 nm) showed certain cytotoxicity, as shown in Figure 5b.
  • the Live-dead reagent and the cell bright field morphology showed that the experimental group ( ⁇ -CRI+808 nm) showed the ability to cause tumor cell apoptosis, as shown in Figure 5c.
  • the experimental group ( ⁇ -CRI+808 nm) has a good ability to inhibit the proliferation and migration of tumor cells, as shown in Figure 5d.
  • CRI and ⁇ -CRI were diluted with PBS to a concentration of 100 ⁇ 200 ⁇ L, and CRI or ⁇ -CRI was injected into the tail vein. After 4 hours, 808 nm light (0.5W/ cm2 , 3 minutes) or no light (protected from light) was applied. The flow chart is shown in Figure 6a. The tumor size was then measured every day. On the 15th day, the mice were photographed and the tumors were removed. The size comparison of the tumors on the back of the mice on the 15th day is shown in Figure 6b, and the size of the in vitro tumors on the 15th day is shown in Figure 6c. The tumors in the experimental group ( ⁇ -CRI +808 nm) were very small.
  • Figure 6d is the tumor inhibition curve
  • Figure 6e is the survival period curve.
  • the survival period of all mice in the experimental group ( ⁇ -CRI +808 nm) was at least 15 days. (Group1:Control; Group2: Control +808 nm; Group3:CRI; Group4:CRI+808 nm; Group5: ⁇ -CRI; Group6: ⁇ -CRI +808 nm).
  • 4T1 cells (2 ⁇ 10 5 ) were inoculated into the left and right flanks of Balb/c mice.
  • CRI and ⁇ -CRI were diluted with PBS to a concentration of 100 ⁇ 200 ⁇ L, respectively.
  • CRI or ⁇ -CRI was injected into the tail vein. After 4 hours, 808 nm light (0.5W/cm 2 , 3 minutes) was given or no light irradiation was performed.
  • Tumor tissues were extracted and stained with hematoxylin-eosin (H&E). Qualitative histological examination of the resected tumor sections showed that no obvious malignant necrosis was observed in the tumors of the control group.
  • H&E hematoxylin-eosin
  • the present invention designs and synthesizes a novel tumor-anchored integrated diagnosis and treatment probe, which has the ability to undergo a cross-linking reaction with RNA in the cytoplasm under the mediation of singlet oxygen, thereby achieving long-window-period imaging of tumor tissues.
  • cross-linking RNA causes severe mitochondrial damage in tumor cells and leads to apoptosis, thus achieving integrated diagnosis and treatment of tumors, as shown in FIG7 .

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Abstract

L'invention concerne une sonde fluorescente de type à ancrage d'acide nucléique intégrée au diagnostic et au traitement, son procédé de préparation et son utilisation. La sonde fluorescente peut générer spontanément de l'oxygène singulet et subir une réaction de réticulation avec de l'ARN dans des cellules sous la médiation de l'oxygène singulet, ce qui permet d'obtenir une imagerie des tissus tumoraux sur une longue période de temps ; en outre, après la réticulation de l'ARN, un dommage de fonction mitochondriale est provoqué et induit en outre une apoptose grave dans des cellules tumorales, ce qui permet d'obtenir un diagnostic et une intégration de traitement de tumeurs.
PCT/CN2023/077769 2023-01-18 2023-02-23 Sonde fluorescente de type à ancrage d'acide nucléique intégrée au diagnostic et au traitement, son procédé de préparation et son utilisation Ceased WO2024152405A1 (fr)

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Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN118930523A (zh) * 2024-08-16 2024-11-12 苏州大学 一种蛋白锚定型铜响应光声探针及其制备方法与应用

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106749153A (zh) * 2016-12-19 2017-05-31 华东理工大学 硝基还原酶的特异性荧光探针及其制备和用于肿瘤靶向荧光成像和监测肿瘤缺氧程度的应用
CN110804087A (zh) * 2019-09-24 2020-02-18 浙江工业大学 一种整合素αvβ3靶向的AIE荧光化合物及其制备与应用
WO2020184806A1 (fr) * 2019-03-11 2020-09-17 서울대학교병원 Sonde de ciblage d'intégrine αvβ3 permettant de diagnostiquer des maladies néovasculaires rétiniennes et choroïdienne, et méthode de préparation associé
CN112592386A (zh) * 2020-11-12 2021-04-02 苏州大学 红光介导的核酸锚定型荧光探针及其制备方法和应用

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105694851B (zh) * 2016-03-08 2018-07-27 武汉大学 一种肿瘤靶向诊疗荧光探针
CN113527416A (zh) * 2021-08-11 2021-10-22 南开大学 一种硝基还原酶响应氨基酸及肿瘤乏氧荧光探针的制备方法

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106749153A (zh) * 2016-12-19 2017-05-31 华东理工大学 硝基还原酶的特异性荧光探针及其制备和用于肿瘤靶向荧光成像和监测肿瘤缺氧程度的应用
WO2020184806A1 (fr) * 2019-03-11 2020-09-17 서울대학교병원 Sonde de ciblage d'intégrine αvβ3 permettant de diagnostiquer des maladies néovasculaires rétiniennes et choroïdienne, et méthode de préparation associé
CN110804087A (zh) * 2019-09-24 2020-02-18 浙江工业大学 一种整合素αvβ3靶向的AIE荧光化合物及其制备与应用
CN112592386A (zh) * 2020-11-12 2021-04-02 苏州大学 红光介导的核酸锚定型荧光探针及其制备方法和应用

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
ALMA R. MORALES, CICERON O. YANEZ, KATHERINE J. SCHAFER-HALES, ADAM I. MARCUS, KEVIN D. BELFIELD: "Biomolecule Labeling and Imaging with a New Fluorenyl Two-Photon Fluorescent Probe", BIOCONJUGATE CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 20, no. 10, 21 October 2009 (2009-10-21), US , pages 1992 - 2000, XP055417382, ISSN: 1043-1802, DOI: 10.1021/bc900302t *
CAO JIE, WAN SHUNAN, TIAN JUNMEI, LI SIWEN, DENG DAWEI, QIAN ZHIYU, GU YUEQING: "Fast clearing RGD‐based near‐infrared fluorescent probes for in vivo tumor diagnosis", CONTRAST MEDIA & MOLECULAR IMAGING, JOHN WILEY & SONS,, GB, vol. 7, no. 4, 1 July 2012 (2012-07-01), GB , pages 390 - 402, XP093194631, ISSN: 1555-4309, DOI: 10.1002/cmmi.1464 *
LI YANING, NIE JUNFANG, DAI JIE, YIN JUN, HUANG BINBIN, LIU JIA, CHEN GUOGUANG, REN LILI: "pH/Redox Dual-Responsive Drug Delivery System with on-Demand RGD Exposure for Photochemotherapy of Tumors", INTERNATIONAL JOURNAL OF NANOMEDICINE, DOVE MEDICAL PRESS, NEW ZEALAND, vol. 17, 23 November 2022 (2022-11-23), New Zealand , pages 5621 - 5639, XP093194633, ISSN: 1178-2013, DOI: 10.2147/IJN.S388342 *
WU QI-LONG, XU HE-LIN, XIONG CUI, LAN QING-HUA, FANG MING-LING, CAI JIN-HUA, LI HUI, ZHU SHU-TING, XU JING-HONG, TAO FANG-YI, LU C: "c(RGDyk)-modified nanoparticles encapsulating quantum dots as a stable fluorescence probe for imaging-guided surgical resection of glioma under the auxiliary UTMD", ARTIFICIAL CELLS, NANOMEDICINE AND BIOTECHNOLOGY, TAYLOR & FRANCIS INC., US, vol. 48, no. 1, 1 January 2020 (2020-01-01), US , pages 143 - 158, XP093194632, ISSN: 2169-1401, DOI: 10.1080/21691401.2019.1699821 *

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