WO2023092708A1 - Complexe de riboflavine pénétrant dans les cellules et son application dans la préparation d'un médicament de thérapie photodynamique - Google Patents

Complexe de riboflavine pénétrant dans les cellules et son application dans la préparation d'un médicament de thérapie photodynamique Download PDF

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WO2023092708A1
WO2023092708A1 PCT/CN2021/137632 CN2021137632W WO2023092708A1 WO 2023092708 A1 WO2023092708 A1 WO 2023092708A1 CN 2021137632 W CN2021137632 W CN 2021137632W WO 2023092708 A1 WO2023092708 A1 WO 2023092708A1
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riboflavin
cell
penetrating
arg
complex
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Chinese (zh)
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房丽晶
武春雷
李艳艳
成哲弘
马智龙
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深圳先进技术研究院
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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
    • A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
    • 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
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • 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
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the invention relates to the field of medicinal chemistry, in particular to a cell-penetrating riboflavin complex and its application in the preparation of photodynamic therapy drugs.
  • Photodynamic therapy is a modern, non-invasive new cancer treatment method, which has the advantages of minimally invasive, targeted, low toxicity, and no drug resistance.
  • photodynamic therapy as a non-surgical alternative therapy has been widely used in the treatment of malignant tumors.
  • Photodynamic therapy relies on the interaction between light source and photosensitizer to generate reactive oxygen species (ROS), which act on proteins, nucleic acids and other biomolecules and destroy their structures, eventually causing cell death.
  • ROS reactive oxygen species
  • photosensitizers play an important role.
  • Some photosensitizers reported so far, such as hematoporphyrin have disadvantages such as poor water solubility and high toxicity and side effects. Therefore, the development of a naturally derived photosensitizer with good biocompatibility, economy and non-toxicity has attracted widespread attention of researchers.
  • Riboflavin also known as vitamin B2
  • Riboflavin is an essential vitamin for the human body, and is an important part of the prosthetic group of flavin enzymes in the body.
  • riboflavin plays an important role in improving the metabolism of organisms and promoting the growth and development of the human body.
  • Riboflavin consists of an isoallazine nucleus and a D-glycosyl chain. The isoalloxazine structure makes riboflavin absorb strongly at 375nm and 445nm and emit fluorescence at 550nm. It is reported that riboflavin has certain photodynamic properties and is an important photosensitizer.
  • riboflavin Under the irradiation of blue light or ultraviolet light, riboflavin can undergo complex photochemical reactions with amino acids, proteins, DNA, etc., causing damage to the structure and function of biomolecules. Riboflavin in the triplet excited state can react photochemically with oxidizable substrates or oxygen molecules to generate reactive oxygen species (ROS), such as OH ⁇ , 1 O 2 .
  • ROS reactive oxygen species
  • riboflavin has been widely used in the treatment of pathogen destruction, inactivation of viruses and bacteria.
  • riboflavin has also been paid attention to, but the uptake of riboflavin by various tumor cells is very low, and under blue light irradiation, riboflavin is non-toxic to these types of cells. Therefore, there is an urgent need for riboflavin to effectively penetrate cells, enhance the phototoxicity of riboflavin, and develop riboflavin into a natural source of biocompatible, low-toxic anti-tumor photodynamic therapy drugs. .
  • the present invention proposes a cell-penetrating riboflavin complex and its application in the preparation of photodynamic therapy drugs.
  • Riboflavin was coupled with cell-penetrating peptides Arg 8 , (Cha-Arg) 3 , and targeting small molecule triphenylphosphine (TPP), and Arg 8 -RF, (Cha-Arg) 3 -RF and TPP-RF three complexes.
  • the invention provides a cell-penetrating riboflavin complex, including riboflavin and its functional ligand, wherein the functional ligand is any one of cell penetrating peptide and triphenylphosphine.
  • cell-penetrating peptide is an arginine-rich polypeptide.
  • cell-penetrating peptide is a hexapeptide composed alternately of cyclohexylalanine and arginine.
  • arginine-rich polypeptide is Arg 8 .
  • the present invention also provides a method for preparing the cell-penetrating riboflavin complex, coupling riboflavin with the functional ligand to synthesize a riboflavin-functional ligand complex, the riboflavin-
  • the functional ligand complex is any one of cell penetrating peptide-riboflavin and triphenylphosphine-riboflavin.
  • the invention also provides the application of the cell-penetrating riboflavin complex in the preparation of photodynamic therapy drugs.
  • the present invention improves the cell uptake efficiency of riboflavin by coupling functional ligands, enhances the photosensitivity toxicity of riboflavin to tumor cells, and enhances the photodynamic therapy effect of riboflavin.
  • the riboflavin complex of the present invention can be used to prepare a naturally derived anti-tumor photodynamic therapy drug, which has the advantages of good biocompatibility, low toxicity, and easy economic availability.
  • Figure 1 is the structure (A) and synthetic route (B) of riboflavin complex.
  • Figure 2 shows the degradation of tyrosine-containing peptides and proteins by riboflavin.
  • A, B Degradation of peptides by riboflavin under blue light irradiation.
  • C Degradation of tyrosine-containing proteins by riboflavin under blue light irradiation.
  • D Photoproducts of riboflavin.
  • Figure 3 shows cellular uptake of riboflavin and riboflavin complexes.
  • Figure 4 shows the cytotoxicity of riboflavin and riboflavin complexes.
  • Figure 5 is the measurement of intracellular ROS.
  • Figure 6 is the analysis of mitochondrial membrane potential.
  • Fig. 7 is the HRMS spectrum of compound RF-COOH (4).
  • Fig. 8 is the HRMS spectrum of compound RF-Ma(5).
  • Fig. 9 is the HRMS spectrum of compound Arg 8 -RF(1).
  • Fig. 10 is the HRMS spectrum of compound (Cha-Arg) 3 -RF(2).
  • Fig. 11 is the HRMS spectrum of compound TPP-NH 2 (8).
  • Fig. 12 is the HRMS spectrum of compound TPP-RF (3).
  • Fig. 13 is the HPLC analysis of the riboflavin complex Arg 8 -RF(1).
  • Figure 14 is the HPLC analysis of riboflavin complex (Cha-Arg) 3 -RF(2).
  • Figure 15 is the HPLC analysis of riboflavin complex TPP-RF(3).
  • Riboflavin is a kind of photosensitizer with good biocompatibility, non-toxic, natural and easy to obtain.
  • riboflavin is an essential vitamin for the human body, the concentration of riboflavin in cells is very low, so the photosensitization effect of riboflavin in the human body is very small.
  • Increasing the concentration of riboflavin in cells is expected to develop riboflavin into a photodynamic therapy drug with significant antitumor activity. It has been proved that under the irradiation of visible light, riboflavin can oxidize A ⁇ 1-42, leading to the attenuation of A ⁇ 1-42 aggregation ability and neurotoxicity.
  • riboflavin have optical waveguide and photosensitive properties, and the riboflavin nanocrystals can kill tumor cells under light conditions.
  • Previous studies have found that PC3, HeLa, MDA-MB-231, A549, U-87 and other tumor cells have very low uptake of riboflavin, and riboflavin is non-toxic to these types of cells under blue light irradiation . Therefore, it is possible to use delivery tools such as cell-penetrating peptides and targeting molecules to improve the cell entry efficiency of riboflavin, which can enhance the photosensitive toxicity of riboflavin, and it is expected to develop riboflavin into a natural source of biocompatibility. , low toxicity anti-tumor photodynamic therapy drugs.
  • riboflavin As photosensitizer and enhance their cell uptake efficiency.
  • the present invention finds that polypeptides rich in arginine (Arg) such as Arg 8 can be used as a delivery tool to improve the ability of drugs and nanomaterials to enter cells.
  • Arg arginine
  • a hexapeptide consisting alternately of cyclohexylalanine (Cha) and Arg can efficiently enter cells and distribute in the cytoplasm.
  • Arg 8 -RF and (Cha-Arg) 3 -RF complexes were synthesized by using cell penetrating peptides Arg 8 and (Cha-Arg) 3 as delivery ligands.
  • the present invention couples the mitochondrial targeting molecule triphenylphosphine (TPP) with riboflavin to synthesize the complex TPP-RF.
  • TPP triphenylphosphine
  • the present invention utilizes the cell-penetrating peptide Arg 8 , (Cha-Arg) 3 and the mitochondrial targeting molecule triphenylphosphine (TPP) as delivery ligands to enhance the cell entry efficiency of riboflavin, and designs and synthesizes Arg 8 -RF , (Cha-Arg) 3 -RF and TPP-RF three complexes, by investigating the cell uptake efficiency and cytotoxicity of the complexes, analyzing the mechanism of inducing cell death, and screening the anti Photodynamic therapy drugs for tumors provide a new strategy for the drug development of riboflavin from natural sources.
  • TPP triphenylphosphine
  • the present invention provides a cell-penetrating riboflavin complex, and evaluates its cell uptake efficiency and photodynamic therapy effect.
  • the method comprises the following steps: (1) degradation of peptides and proteins by riboflavin; (2) synthesis of riboflavin complexes Arg 8 -RF, (Cha-Arg) 3 -RF and TPP-RF (3) cellular uptake (4) Study on the effect of anti-tumor photodynamic therapy; (5) Evaluation of cytotoxicity; (6) Generation of intracellular ROS; (7) Analysis of mitochondrial membrane potential.
  • the PBS solution containing green fluorescent protein (GFP, 1 ⁇ M) and riboflavin (10 ⁇ M) was irradiated with LED light for 20 min, and then the reaction solution was analyzed by electrophoresis, and the results are shown in FIG. 2 .
  • the degradation of peptides and proteins by riboflavin shows that riboflavin can degrade polypeptides rich in histidine, tryptophan and tyrosine, and can degrade proteins such as insulin and green fluorescent protein rich in tyrosine. It shows that riboflavin can destroy the structure of polypeptide and protein and damage its function, so it is expected to become a photodynamic therapy drug of natural origin.
  • Step 3 Synthesis of Arg 8 -RF (1) and (Cha-Arg) 3 -RF (2).
  • RF-Ma 3.mg, 0.005mmol
  • TEA 0.05mmol, 7 ⁇ L
  • thiol-containing penetrating peptide HS-Arg 8 (6) (13.5mg, 0.01mmol
  • HS-(Cha-Arg) 3 (7) 10 mg, 0.01 mmol.
  • the mixture was stirred for 2 h under ice-bath conditions, and the reaction solution was purified by RP-HPLC.
  • TPP-RF (3) Synthesis of TPP-RF (3).
  • RF-COOH (4) (4.2mg, 0.0083mmol) and HATU (3.56mg, 0.0083mmol) were dissolved in anhydrous DMF (500 ⁇ L), then DIEA (30 ⁇ L, 0.166mmol) was added for activation for 1min, and then added to the activation solution TPP- NH2 (8) (4 mg, 0.0083 mmol).
  • the reaction mixture was stirred at room temperature for 1 h and purified by RP-HPLC.
  • the collected product was lyophilized to obtain TPP-RF (3) (7 mg, 87.5%).
  • the HPLC results of TPP-RF(3) are shown in Figure 15 and Table 3.
  • HeLa cells were seeded in 12-well plates and incubated for 24 h. Riboflavin and riboflavin complexes Arg 8 -RF, (Cha-Arg) 3 -RF and TPP-RF were prepared in culture medium to 25 ⁇ M, added to cells respectively, and incubated at 37°C for 2 hours. The nuclei were stained with Hoechst 33258 (10 ⁇ g/mL) for 30 min. After the staining, the excess dye was washed away with PBS, and the cells were fixed with 4% paraformaldehyde for 15 min, and finally the fluorescence imaging was performed with Olympus Qlmaging Retiga R6.
  • Riboflavin and riboflavin complexes were excited with 488nm blue light, and their fluorescence was monitored in the green light channel, and the results are shown in Figure 3.
  • the cell uptake experiment showed that the cell uptake efficiency of riboflavin is extremely low, and it has no cytotoxicity under light conditions; after riboflavin is coupled with functional molecules to form a complex, (Cha-Arg) 3 -RF can enter cells in large quantities, Arg 8 -RF accumulates little in cells, while TPP-RF cannot enter cells.
  • HeLa cells were seeded in 12-well plates and incubated for 24 h. Riboflavin and riboflavin complex (Cha-Arg) 3 -RF were prepared in a culture medium to 25 ⁇ M, and added to the cells for incubation for 4 hours. Then the drug was sucked off, PBS was added, and blue light was irradiated for 20 minutes. After the light was over, the cells were stained with PI (50 ⁇ g/mL) and Hoechst 33258. After incubating for 30 min, the staining solution was washed away, and new medium was added, and imaged with a fluorescent microscope Olympus BX63.
  • PI 50 ⁇ g/mL
  • Hoechst 33258 Hoechst 33258
  • HeLa cells were seeded in 12-well plates and incubated for 24 h. Riboflavin and riboflavin complex (Cha-Arg) 3 -RF were prepared in a culture medium to 10 ⁇ M, and added to the cells for incubation for 4 hours. The drug was then aspirated, and the ROS probe H2DCFDA (10 ⁇ g/mL) was added. After incubation for 1 h, wash with PBS three times, and add PBS for light. After irradiating for 10 min, the cells were stained with Hoechst 33258. After incubating for 30 min, the staining solution was washed away, and new medium was added, and imaged with a fluorescent microscope Olympus BX63.
  • H2DCFDA was excited with 488nm blue light, and its fluorescence was monitored in the green light channel, and the results are shown in Figure 5.
  • the measurement and analysis of intracellular ROS showed that (Cha-Arg) 3 -RF produced ROS under blue light irradiation, and ROS could non-selectively destroy protein structure and function, cause mitochondrial damage, and finally induce cell death.
  • HeLa cells were seeded in 12-well plates and incubated for 24 h. Riboflavin and riboflavin complex (Cha-Arg) 3 -RF were prepared in a culture medium to 10 ⁇ M, and added to the cells for incubation for 4 hours. Then the drug was sucked off, PBS was added, and blue light was irradiated for 10 min. After the end of the light, the cells were stained with mitochondrial membrane potential analysis dye TMRE (10 ⁇ M) and Hoechst 33258. After incubating for 30 min, the staining solution was washed away, and new medium was added, and imaged with a fluorescent microscope Olympus BX63.
  • TMRE mitochondrial membrane potential analysis dye
  • TMRE was excited with 560nm green light, and its fluorescence was monitored in the red light channel, and the results are shown in Figure 6.
  • the analysis of mitochondrial membrane potential in cells showed that (Cha-Arg) 3 -RF produced ROS under blue light irradiation, and ROS could non-selectively destroy protein structure and function, cause mitochondrial damage, and finally induce cell death.
  • the functional ligands used in the present invention can be replaced by other functional groups such as tumor-targeting molecules and tumor-targeting peptides, such as folic acid, targeting peptides, nucleic acid aptamers, and targeting fluorescent dyes;
  • riboflavin can be replaced by nuclear Flavin derivatives such as flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD), light pigment (lumichrome), riboflavin tetrabutyrate, etc. instead.
  • FMN flavin mononucleotide
  • FAD flavin adenine dinucleotide
  • light pigment lumichrome
  • riboflavin tetrabutyrate etc.
  • the present invention discloses a cell-penetrating riboflavin complex and its application in the preparation of photodynamic therapy drugs.
  • Riboflavin was coupled with cell-penetrating peptides Arg 8 , (Cha-Arg) 3 , and targeting small molecule triphenylphosphine (TPP), and Arg 8 -RF, (Cha-Arg) 3 -RF and TPP-RF three complexes, by comparing their cell uptake efficiency and photosensitivity toxicity, (Cha-Arg) 3 -RF can improve the uptake efficiency of riboflavin by tumor cells, and at the same time enhance the photodynamic therapy effect of riboflavin.
  • the riboflavin complex of the invention can be used to prepare a naturally derived anti-tumor photodynamic therapy drug, and the drug has the advantages of good biocompatibility, low toxicity, easy economical availability and the like.

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Abstract

Complexe de riboflavine pénétrant dans les cellules et son application dans la préparation d'un médicament de thérapie photodynamique. La riboflavine est couplée à un peptide de pénétration cellulaire Arg8, (Cha-Arg)3, et une petite molécule cible de triphénylphosphine (TPP), respectivement ; trois complexes comprenant Arg8-RF, (Cha-Arg)3-RF et TPP-RF sont conçus, et par comparaison de l'efficacité d'absorption cellulaire et de la phototoxicité de ceux-ci, (Cha-Arg)3-RF peut améliorer l'efficacité d'absorption de cellules tumorales vis-à-vis de la riboflavine ; pendant ce temps, l'effet thérapeutique photodynamique de la riboflavine est amélioré. Le complexe de riboflavine peut être utilisé pour préparer un médicament de thérapie photodynamique anti-tumeur d'origine naturelle. Le médicament présente les avantages d'être de bonne biocompatibilité, de faible toxicité, économique et facilement disponible.
PCT/CN2021/137632 2021-11-25 2021-12-13 Complexe de riboflavine pénétrant dans les cellules et son application dans la préparation d'un médicament de thérapie photodynamique WO2023092708A1 (fr)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050176624A1 (en) * 2003-08-07 2005-08-11 Thompson Mark E. Organometallic complexes as singlet oxygen sensitizers
CN104940950A (zh) * 2015-07-09 2015-09-30 武汉大学 一种肿瘤靶向多肽光敏剂键合物
US20150374714A1 (en) * 2013-02-11 2015-12-31 University Of Georgia Research Foundation, Inc. Generation of functional dendritic cells
CN107936091A (zh) * 2017-11-13 2018-04-20 中南大学湘雅三医院 一种靶向细胞穿膜肽光敏剂及其制备方法和应用

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050176624A1 (en) * 2003-08-07 2005-08-11 Thompson Mark E. Organometallic complexes as singlet oxygen sensitizers
US20150374714A1 (en) * 2013-02-11 2015-12-31 University Of Georgia Research Foundation, Inc. Generation of functional dendritic cells
CN104940950A (zh) * 2015-07-09 2015-09-30 武汉大学 一种肿瘤靶向多肽光敏剂键合物
CN107936091A (zh) * 2017-11-13 2018-04-20 中南大学湘雅三医院 一种靶向细胞穿膜肽光敏剂及其制备方法和应用

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
HORTON, K.L. ; STEWART, K.M. ; FONSECA, S.B. ; GUO, Q. ; KELLEY, S.O.: "Mitochondria-Penetrating Peptides", CHEMISTRY & BIOLOGY, vol. 15, no. 4, 21 April 2008 (2008-04-21), GB , pages 375 - 382, XP022613220, ISSN: 1074-5521, DOI: 10.1016/j.chembiol.2008.03.015 *
MAHALINGAM SAKKARAPALAYAM M, ORDAZ JOSUE D., LOW PHILIP S: "Targeting of a Photosensitizer to the Mitochondrion Enhances the Potency of Photodynamic Therapy", ACS OMEGA, vol. 3, no. 6, 30 June 2018 (2018-06-30), US , pages 6066 - 6074, XP093069425, ISSN: 2470-1343, DOI: 10.1021/acsomega.8b00692 *
YONGDOO CHOI; JASON R. MCCARTHY; RALPH WEISSLEDER; CHING‐HSUAN TUNG: "Conjugation of a Photosensitizer to an Oligoarginine‐Based Cell‐Penetrating Peptide Increases the Efficacy of Photodynamic Therapy", CHEMMEDCHEM COMMUNICATIONS, vol. 1, no. 4, 24 January 2006 (2006-01-24), DE , pages 458 - 463, XP072419295, ISSN: 1860-7179, DOI: 10.1002/cmdc.200500036 *

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