Sulfonated Aluminum Phthalocyanine Research Articles

Configurationally Confined Multilevel Supramolecular Assemblies for Modulating Multicolor Luminescence

AbstractHerein, multilevel supramolecular assemblies are reported based on sulfobutylether‐β‐cyclodextrin (SBE‐βCD) and cucurbit[8]uril (CB[8]), which can control the topological morphology from nanoparticles to nanosheets and modulate the multicolor luminescence. Benefiting from the large cavity of CB[8] and its strong binding affinity with positively charged tetraphenylethylene pyridinium (TPE‐Py), a 1:2 stoichiometric supramolecular assembly is formed through host–guest interactions with binding constants of 2.95 × 1011 M−2 and fluorescence bathochromic shift about 35 nm due to the macrocyclic confinement effect, thereby endowing the fluorescence enhancement about 20 times when further assembled with negatively charged SBE‐βCD to form nanosheets through electrostatic interactions. In contrast, the direct assembly of TPE‐Py and SBE‐βCD can form nanoparticles through electrostatic interactions, showing only tenfold enhancement and no bathochromic shift due to the lack of macrocyclic confinement effect. After doping the near‐infrared dye acceptor sulfonated aluminum phthalocyanine (AlPcS4), the nanosheets structure exhibits a higher energy transfer efficiency of about 75% and a larger antenna effect of 29.3 than that of nanoparticles. The multilevel supramolecular assemblies can be used in multicolor luminescence information storage and multiple logical gate systems, providing an efficient approach for configurationally confined topological morphology regulation and luminescent materials.

Folic Acid-Modified Cyclodextrin Multivalent Supramolecular Assembly for Photodynamic Therapy.

The construction of supramolecular multivalent assemblies with unique photoluminescence behaviors and biological functions has become a research hot spot recently in the biomaterial field. Herein, we report an adaptive supramolecular assembly via a multivalent co-assembly strategy prepared in two stages by using an adamantane-connected pyrenyl pyridinium derivative (APA2), sulfonated aluminum phthalocyanine (PcS), and folic acid-modified β-cyclodextrin (FA-CD) for efficient dual-organelle targeted photodynamic cancer cell ablation. Benefiting from π-π and electrostatic interactions, APA2 and PcS could first assemble into non-fluorescent irregular nanoaggregates because of the heterodimer aggregation-induced quenching and then secondarily assemble with FA-CD to afford targeted spherical nanoparticles (NPs) with an average diameter of around 50 nm, which could be specifically taken up by HeLa cancer cells through endocytosis in comparison with 293T normal cells. Intriguingly, such multivalent NPs could adaptively disaggregate in an intracellular physiological environment of cancer cells and further respectively and selectively accumulate in mitochondria and lysosomes, which not only displayed near-infrared two-organelle localization in situ but also aroused efficient singlet oxygen generation under light irradiation to effectively eliminate cancer cells up to 99%. This supramolecular multivalent assembly with an adaptive feature in a specific cancer cell environment provides a feasible strategy for precise organelle-targeted imaging and an efficiently synergetic photodynamic effect in situ for cancer cell ablation.

CASTING: A Potent Supramolecular Strategy to Cytosolically Deliver STING Agonist for Cancer Immunotherapy and SARS-CoV-2 Vaccination

CASTING: A Potent Supramolecular Strategy to Cytosolically Deliver STING Agonist for Cancer Immunotherapy and SARS-CoV-2 Vaccination

Coassembly of hypoxia-sensitive macrocyclic amphiphiles and extracellular vesicles for targeted kidney injury imaging and therapy

BackgroundHypoxia is a major contributor to global kidney diseases. Targeting hypoxia is a promising therapeutic option against both acute kidney injury and chronic kidney disease; however, an effective strategy that can achieve simultaneous targeted kidney hypoxia imaging and therapy has yet to be established. Herein, we fabricated a unique nano-sized hypoxia-sensitive coassembly (Pc/C5A@EVs) via molecular recognition and self-assembly, which is composed of the macrocyclic amphiphile C5A, the commercial dye sulfonated aluminum phthalocyanine (Pc) and mesenchymal stem cell-excreted extracellular vesicles (MSC-EVs).ResultsIn murine models of unilateral or bilateral ischemia/reperfusion injury, MSC-EVs protected the Pc/C5A complex from immune metabolism, prolonged the circulation time of the complex, and specifically led Pc/C5A to hypoxic kidneys via surface integrin receptor α4β1 and αLβ2, where Pc/C5A released the near-infrared fluorescence of Pc and achieved enhanced hypoxia-sensitive imaging. Meanwhile, the coassembly significantly recovered kidney function by attenuating cell apoptosis, inhibiting the progression of renal fibrosis and reducing tubulointerstitial inflammation. Mechanistically, the Pc/C5A coassembly induced M1-to-M2 macrophage transition by inhibiting the HIF-1α expression in hypoxic renal tubular epithelial cells (TECs) and downstream NF-κB signaling pathway to exert their regenerative effects.ConclusionThis synergetic nanoscale coassembly with great translational potential provides a novel strategy for precise kidney hypoxia diagnosis and efficient kidney injury treatment. Furthermore, our strategy of coassembling exogenous macrocyclic receptors with endogenous cell-derived membranous structures may offer a functional platform to address multiple clinical needs.Graphical

Development of multifunctional nanocomposites for controlled drug delivery and hyperthermia

Magnetic nano/micro-particles based on clinoptilolite-type of natural zeolite (CZ) were fabricated and were expected to act as carriers for controlled drug delivery/release, imaging and local heating in biological systems. Adsorption of rhodamine B, sulfonated aluminum phthalocyanine and hypericin by magnetic CZ nano/micro-particles was investigated, as was the release of hypericin. Using an alternating magnetic field, local temperature increase by 10 °C in animal tissue with injected magnetic CZ particles was demonstrated. In addition, the CZ-based particles have been found to exhibit an anti-amyloidogenic effect on the amyloid aggregation of insulin and lysozyme in a dose- and temperature-dependent manner. Therefore, the mesoporous structure of CZ particles provided a unique platform for preparation of multifunctional magnetic and optical probes suitable for optical imaging, MRI, thermo- and phototherapy and as effective containers for controlled drug delivery. We concluded that magnetic CZ nano/micro-particles could be evaluated for further application in cancer hyperthermia therapy and as anti-amyloidogenic agents.

Permanent Photodynamic Activation of the Cholecystokinin 2 Receptor.

The cholecystokinin 2 receptor (CCK2R) is expressed in the central nervous system and peripheral tissues, playing an important role in higher nervous and gastrointestinal functions, pain sensation, and cancer growth. CCK2R is reversibly activated by cholecystokinin or gastrin, but whether it can be activated permanently is not known. In this work, we found that CCK2R expressed ectopically in CHO-K1 cells was permanently activated in the dark by sulfonated aluminum phthalocyanine (SALPC/AlPcS4, 10–1000 nM), as monitored by Fura-2 fluorescent calcium imaging. Permanent CCK2R activation was also observed with AlPcS2, but not PcS4. CCK2R previously exposed to SALPC (3 and 10 nM) was sensitized by subsequent light irradiation (>580 nm, 31.5 mW·cm−2). After the genetically encoded protein photosensitizer mini singlet oxygen generator (miniSOG) was fused to the N-terminus of CCK2R and expressed in CHO-K1 cells, light irradiation (450 nm, 85 mW·cm−2) activated in-frame CCK2R (miniSOG-CCK2R), permanently triggering persistent calcium oscillations blocked by the CCK2R antagonist YM 022 (30 nM). From these data, it is concluded that SALPC is a long-lasting CCK2R agonist in the dark, and CCK2R is photogenetically activated permanently with miniSOG as photosensitizer. These properties of SALPC and CCK2R could be used to study CCK2R physiology and possibly for pain and cancer therapies.

A highly efficient light-harvesting system with sequential energy transfer based on a multicharged supramolecular assembly.

A supramolecular assembly was constructed by the nonconvalent interaction of pillar[5]arene (WP5) with a pyridinium modified tetraphenylethene (Py-TPE) derivative, in which Py-TPE/WP5 acted as a donor, and sulforhodamine 101 and sulfonated aluminum phthalocyanine acted as acceptors to realize a highly efficient light-harvesting system with two-step sequential energy transfer.

Complexation of a guanidinium-modified calixarene with diverse dyes and investigation of the corresponding photophysical response.

We herein describe the comprehensive investigation of the complexation behavior of a guanidinium-modified calix[5]arene pentaisohexyl ether (GC5A) with a variety of typical luminescent dyes. Fluorescein, eosin Y, rose bengal, tetraphenylporphine sulfonate and sulfonated aluminum phthalocyanine were employed as classical aggregation-induced quenching dyes. 2-(p-Toluidinyl)naphthalene-6-sulfonic acid and 1-anilinonaphthalene-8-sulfonic acid were selected as representatives of intramolecular charge-transfer dyes. Phosphated tetraphenylethylene was involved as the classical aggregation-induced emission dye. Sulfonated acedan representing one example of two-photon fluorescent probes, was also investigated. A ruthenium(II) complex with carboxylated bipyridyl ligands was included as a representative candidate of luminescent transition-metal complexes. We determined the association constants of the GC5A–dye complexes by fluorescence titration and discuss the complexation-induced photophysical changes. In addition, a comparison of the complexation behavior of GC5A with that of other macrocycles and potential applications according to the diverse photophysical responses are provided.

Aspect ratio dependence of the enhancement of fluorescence intensity by gold nanobipyramids for cancer cell imaging and photodynamic therapy

Enhancement of dye fluorescence intensity was studied by modifying the aspect ratio of gold nanobipyramids (AuBPs) from 3.2 to 6.6. The emission fluorescence intensity of sulfonated aluminum phthalocyanine (AlPcS) was strongly dependent on the aspect ratio of AuBPs. Furthermore, we found that the energy transfer from excited AlPcS to AuBPs was a key determinant of the efficacy of metal-enhanced fluorescence. By means of AuBPs with a higher aspect ratio, such that the surface plasmon resonance band does not overlap with the energy level of excited AlPcS, metal-enhanced fluorescence of various AlPcS–AuBP conjugates was determined, and the maximal enhancement factor was found to be 14. The enhanced fluorescence intensity of AlPcS conjugated with AuBPs indicates promising plasmonic properties. An apoptosis assay of HeLa cells revealed that AlPcS–AuBPs, when used as a drug, can enhance the effectiveness of photodynamic therapy (PDT). Furthermore, AuBPs with the longitudinal absorption peak wavelength of 1050 nm had optimal proapoptotic effects. HeLa cells treated with AlPcS–AuBPs (ratio 0.42 µM to 0.01 nM) had viability as low as 29.31% after 32 J cm−2 ultraviolet light exposure, indicating the strong potential of AlPcS–AuBPs to improve the efficacy of PDT.

Cholecystokinin 1 Receptor – A Unique G Protein-Coupled Receptor Activated by Singlet Oxygen (GPCR-ABSO)

Plasma membrane-delimited generation of singlet oxygen by photodynamic action with photosensitizer sulfonated aluminum phthalocyanine (SALPC) activates cholecystokinin 1 receptor (CCK1R) in pancreatic acini. Whether CCK1R retains such photooxidative singlet oxygen activation properties in other environments is not known. Genetically encoded protein photosensitizers KillerRed or mini singlet oxygen generator (miniSOG) were expressed in pancreatic acinar tumor cell line AR4-2J, CCK1R, KillerRed or miniSOG were expressed in HEK293 or CHO-K1 cells. Cold light irradiation (87 mW⋅cm-2) was applied to photosensitizer-expressing cells to examine photodynamic activation of CCK1R by Fura-2 fluorescent calcium imaging. When CCK1R was transduced into HEK293 cells which lack endogenous CCK1R, photodynamic action with SALPC was found to activate CCK1R in CCK1R-HEK293 cells. When KillerRed or miniSOG were transduced into AR4-2J which expresses endogenous CCK1R, KillerRed or miniSOG photodynamic action at the plasma membrane also activated CCK1R. When fused KillerRed-CCK1R was transduced into CHO-K1 cells, light irradiation activated the fused CCK1R leading to calcium oscillations. Therefore KillerRed either expressed independently, or fused with CCK1R can both activate CCK1R photodynamically. It is concluded that photodynamic singlet oxygen activation is an intrinsic property of CCK1R, independent of photosensitizer used, or CCK1R-expressing cell types. Photodynamic singlet oxygen CCK1R activation after transduction of genetically encoded photosensitizer in situ may provide a convenient way to verify intrinsic physiological functions of CCK1R in multiple CCK1R-expressing cells and tissues, or to actuate CCK1R function in CCK1R-expressing and non-expressing cell types after transduction with fused KillerRed-CCK1R.

Combination of photothermal and photodynamic inactivation of cancer cells through surface plasmon resonance of a gold nanoring

We demonstrate effective inactivation of oral cancer cells SAS through a combination of photothermal therapy (PTT) and photodynamic therapy (PDT) effects based on localized surface plasmon resonance (LSPR) around 1064 nm in wavelength of a Au nanoring (NRI) under femtosecond (fs) laser illumination. The PTT effect is caused by the LSPR-enhanced absorption of the Au NRI. The PDT effect is generated by linking the Au NRI with the photosensitizer of sulfonated aluminum phthalocyanines (AlPcS) for producing singlet oxygen through the LSPR-enhanced two-photon absorption (TPA) excitation of AlPcS. The laser threshold intensity for cancer cell inactivation with the applied Au NRI linked with AlPcS is significantly lower when compared to that with the Au NRI not linked with AlPcS. The comparison of inactivation threshold intensity between the cases of fs and continuous laser illuminations at the same wavelength and with the same average power confirms the crucial factor of TPA under fs laser illumination for producing the PDT effect.

Tat/HA2 Peptides Conjugated AuNR@pNIPAAm as a Photosensitizer Carrier for Near Infrared Triggered Photodynamic Therapy.

To achieve an efficiency of intracellular photosensitizers (PSs) delivery and efficacy of photodynamic therapy, we have developed a novel class of PS formulation for encapsulating sulfonated aluminum phthalocyanine (AlPcS4) by taking advantage of the membrane-disruptive peptides Tat/HA2 and the photothermally triggered delivery system using AuNR@pNIPAAm. The coordinated effects of cell penetrating peptide Tat and fusogenic peptide HA2 could enhance the efficient cellular internalization and endo/lysosome escape of PSs delivery systems. Singlet oxygen generation was inhibited due to the reaction between loaded AlPcS4 and Au nanorods, which indicated that the AlPcS4-loaded, AuNR@pNIPAAm delivery system might be nonphototoxic in the circulatory system. However, this PSs-loaded nanosystem became highly phototoxic as it underwent the near-infrared irradiation by using the combined lights of 808 and 680 nm. Upon irradiation, the Tat/HA2 conjugated AuNR@pNIPAAm-Pc elicited an active photodynamic response against the cancer cells, leading to effective cells killing via mitochondria-associated apoptotic pathway. This study also demonstrated improved PDT therapeutic efficacy after intravenous administration of Tat/HA2-AuNR@pNIPAAm-Pc and the subsequent lights irradiations in tumor-bearing mice. We describe here a strategy for enhanced photodynamic eradication of solid tumors by endo/lysosomal escape and highlight the great promise of peptide-based nanocarriers used for cancer therapy.

Two Orders of Magnitude Fluorescence Enhancement of Aluminum Phthalocyanines by Gold Nanocubes: A Remarkable Improvement for Cancer Cell Imaging and Detection

The metal-enhanced fluorescence (MEF) by metal nanoparticles is a useful technique for fluorescence detections in biological systems. The MEF effects with gold nanorods (AuNRs) and nanocubes (AuNCs) for fluorescence enhancements of sulfonated aluminum phthalocyanine (AlPcS), a commonly used and clinical approved photosensitizer for photodynamic therapy of cancers, were studied in this work. For the AuNRs which have the low aspect ratios with the corresponding longitudinal surface plasma resonance (LSPR) band in the region of 600-750 nm, the fluorescence quenching of conjugated AlPcS was found. Whereas for the AuNRs that have the LSPR bands of 800-900 nm, the MEF of AlPcS was obtained with the enhancing factor of 2-6 times, respectively. Using AuNCs, a great enhancement of AlPcS fluorescence was achieved with an enhancing factor of 150 times. Using two cancer cell lines as in vitro models, an outstanding fluorescence enhancement of AlPcS-AuNCs conjugates in cells, relative to AlPcS alone, was obtained under one-photon excitation (OPE) of 405 nm. Moreover, the bright fluorescence image of AlPcS-AuNCs in cells was also achieved under the two-photon excitation (TPE) of an 800 nm femtosecond laser. The high-quality cell imaging with either OPE or TPE demonstrated the potential of AlPcS-AuNCs in cancer cell detections.

Sulfonated aluminum phthalocyanines for two-photon photodynamic cancer therapy: the effect of the excitation wavelength

Sulfonated aluminum phthalocyanine (AlPcS) is a well-studied photosensitizer which has been widely used in research and in clinical applications of the photodynamic therapy of cancers. Conventionally, one-photon excitation was used, but it was unknown whether two-photon excitation of AlPcS was equally effective. In this study, the two-photon absorption cross sections of AlPcS at near infrared wavelengths were deduced from femtosecond (fs) laser-induced fluorescence. We found that the two-photon absorption cross section of AlPcS was strongly dependent on the excitation wavelength. It was about 19 GM when excited at 800 nm, but grew to 855 GM when excited at 750 nm. The 750 nm fs-laser-induced fluorescence images of AlPcS in human nasopharyngeal carcinoma cells were clearly visible while the corresponding images were very dim when excited at 800 nm. Singlet oxygen production was 13 times higher when excited at 750 nm relative to 800 nm. Our subsequent in vitro experiments showed that 750 nm two-photon excitation with an unfocused fs laser beam damaged cancer cells in a light-dose-dependent manner typical of photodynamic therapy (PDT). The killing at 750 nm was about 9–10 times more efficient than at 800 nm. These results demonstrated for the first time that AlPcS has good potential for two-photon PDT of cancers.

Conjugates of folic acids with zinc aminophthalocyanine for cancer cell targeting and photodynamic therapy by one-photon and two-photon excitations.

To improve the photodynamic detection and therapy of cancers (PDT), folic acid (FA) was conjugated with zinc tetraaminophthalocyanine (ZnaPc) to form ZnaPc-FA. The uptake efficiency of ZnaPc-FA to a FR-positive (folate receptor overexpressed) KB cell line (human nasopharyngeal epidermal carcinoma) was much higher than that of ZnaPc demonstrating an enhanced binding ability of ZnaPc-FA to KB cells. When KB cells were pretreated with free FA followed by incubation of ZnaPc-FA, the high uptake rate of ZnaPc-FA disappeared which demonstrated the special binding function of the FA terminal of ZnaPc-FA on KB cells. The confocal fluorescence images further showed that the affinity of ZnaPc-FA to FR-negative A549 cells (human lung epithelial carcinoma cancer cells) was very low, confirming that ZnaPc-FA can only target FR-positive cancers. The two-photon absorption cross-section of ZnaPc-FA was also higher than that of sulfonated aluminum phthalocyanine (AlPcS), an approved PS for clinical applications. With a 780 nm femto-second (fs) laser, the fluorescence image of ZnaPc-FA in KB cells under two-photon excitation (TPE) can be clearly seen, and the two-photon induced singlet oxygen in ZnaPc-FA solution was found to be proportional to the irradiation dose of the fs laser. The PDT damaging effect of ZnaPc-FA on KB cells was much effective relative to AlPcS under common one-photon excitation, and the killing efficacy of ZnaPc-FA under TPE was 10-fold higher than that of AlPcS. These results suggest that ZnaPc-FA is a promising candidate for PDT improvements and particularly for TPE PDT.

An alternative model for photodynamic therapy of cancers: Hot-band absorption

The sulfonated aluminum phthalocyanine (AlPcS), a photosensitizer for photodynamic cancer therapy (PDT), has an absorption tail in the near-infrared region (700–900 nm) which is so-called hot band absorption (HBA). With the HBA of 800 nm, the up-conversion excitation of AlPcS was achieved followed by the anti-Stocks emission (688 nm band) and singlet oxygen production. The HBA PDT of AlPcS seriously damaged the KB and HeLa cancer cells, with a typical light dose dependent mode. Particularly, the in vitro experiments with the AlPcS shielding solutions further showed that the HBA PDT can overcome a self-shielding effect benefiting the PDT applications.

Femto-second laser beam with a low power density achieved a two-photon photodynamic cancer therapy with quantum dots.

Focusing the femto-second (fs) laser beam on the target was the usual way to carry out a two-photon excitation (TPE) in previous photodynamic therapy (PDT) studies. However, focusing the laser deep inside the tissues of the tumor is unrealistic due to tissue scattering, so that this focusing manner seems unfit for practical TPE PDT applications. In this work, we prepared a conjugate of quantum dots (QDs) and sulfonated aluminum phthalocyanine (AlPcS) for TPE PDT, because QDs have a very high two-photon absorption cross section (TPACS) and thus QDs can be excited by an unfocused 800 nm fs laser beam with a low power density and then transfer the energy to a conjugated AlPcS via fluorescence resonance energy transfer (FRET). The FRET efficiency of the QD-AlPcS conjugate in water was as high as 90%, and the FRET process of the cellular QD-AlPcS was also observed in both KB and HeLa cells under TPE of a 800 nm fs laser. The singlet oxygen (1O2) products were produced by the QD-AlPcS under the TPE of the unfocused 800 nm fs laser via FRET mediated PDT. Moreover, the QD-AlPcS can effectively destroy these cancer cells under the irradiation of the 800 nm unfocused fs laser beam with a power density of 92 mW mm-2, and particularly the killing efficiency of the TPE is comparable to that of the commonly used one-photon excitation (OPE) at visible wavelengths. These results highlight the potential of QD-AlPcS for TPE PDT with a near infrared wavelength.

Dopamine–quantum dot conjugate: a new kind of photosensitizers for photodynamic therapy of cancers

The thiol-capped CdTe quantum dots (QDs) with the average size of 3.5 nm were linked to dopamines (DAs) forming DA–QD conjugates, with the characteristics of red-shifted photoluminescence (PL) peak and remarkably reduced PL lifetime. The QDs in the conjugates readily accept the electron from DAs when excited by the visible light, resulting in the oxidation of DAs and the production of singlet oxygen (1O2) with the yield comparable to that of sulfonated aluminum phthalocyanine (AlPcS), a popularly used photosensitizer. The DA–QD conjugate can quickly penetrate into human nasopharyngeal carcinoma (KB) cells and seriously destroy cells under the irradiation of visible lights, showing the potential to become a new kind of photosensitizers.

Conjugation of sulfonated aluminum phthalocyanine to doxorubicin can improve the efficacy of photodynamic cancer therapy

Sulfonated aluminum phthalocyanine (AlPcS), a widely used photosensitizer for photodynamic therapy of cancer, was conjugated to doxorubicin (Dox), a chemotherapy drug, through electrostatic binding. The fluorescence resonance energy transfer from Dox to AlPcS showed the formation of AlPcS-Dox conjugates, as the fluorescence intensity of conjugated Dox was decreased and that of the AlPcS moiety was enhanced. This AlPcS-Dox conjugation was further confirmed by electrophoresis. The AlPcS-Dox conjugates enhanced the cellular uptake of AlPcS three times more than unconjugated AlPcS in both human hepatocellular carcinoma cell line 7701 and rat basophilic leukemia cell line. Moreover, the photodynamic killing effect of the conjugates was markedly increased as compared with that of AlPcS alone or the cytotoxicity of Dox alone, showing an enhanced effect of the AlPcS-Dox conjugates. These results indicate that the conjugation of a photosensitizer with a chemotherapy drug may improve photodynamic cancer therapy.

A nano complex of hydrophilic phthalocyanine and polyethylenimine for improved cellular internalization efficiency and phototoxicity

To enhance the cellular internalization and phototoxicity of sulfonated aluminum phthalocyanine (AlPcS), a hydrophilic photosensitizer (PS), nano complexes composed of a mixture of AlPcS (negatively charged) and polyethylenimine (PEI; positively charged) with different weight ratios of PEI to AlPcS were prepared via electrostatic interaction. The size of the PEI/AlPcS 0.6 (weight ratio=PEI/AlPcS) was below 200nm with a monodispersed size distribution. The cellular uptake of the complex was determined using a fluorescence image test, a cell lysis test and confocal observation. The cellular internalization of AlPcS in the PEI/AlPcS 0.6 nano complex was 87 times higher than that of free AlPcS after 6h. The photoactivity of the nano complex, as measured by fluorescence intensity and singlet oxygen generation activity in PBS buffer, was completely eliminated by a self-quenching effect. After cellular uptake, the loss of the fluorescence intensity was restored by the dissociation of the nano complex. Additionally, the phototoxicity of the complex, both with and without light irradiation, was investigated using an MTT colorimetric assay. Although the free AlPcS did not exhibit phototoxicity, the nano complex showed strong phototoxicity after irradiation. Therefore, we suggest that the nano complex system has potential use in clinical photodynamic therapy and in the biological study of various cancers.