Two-Photon Responsive Porphyrinic Metal-Organic Framework Involving Fenton-Like Reaction for Enhanced Photodynamic and Sonodynamic Therapy

doi:10.21203/rs.3.rs-1319887/v1

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Two-Photon Responsive Porphyrinic Metal-Organic Framework Involving Fenton-Like Reaction for Enhanced Photodynamic and Sonodynamic Therapy

https://doi.org/10.21203/rs.3.rs-1319887/v1

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Designing new oxygenation nanomaterials by oxygen-generating or oxygen-carrying strategies in hypoxia-associated anti-tumor therapy is a high priority target yet challenge. In this work, we fabricated a nanoplatform involving Fenton-like reaction, Pd@MOF-525@HA, to relieve tumor hypoxia via oxygen-generating strategy for enhanced oxygen-dependent anti-tumor therapy. Thereinto, the porphyrinic MOF-525 can produce singlet oxygen (¹O₂) via light or ultrasonic irradiation for photodynamic and sonodynamic therapy. Notably, the well-dispersed Pd nanocubes within MOF-525 can convert H₂O₂ into O₂ to mitigate the hypoxic environment for enhanced therapy outcome. Moreover, the two-photon activity and cancer cell specific targeting capability of Pd@MOF-525@HA gave rise to deeper tissue penetration and near-infrared light-induced fluorescence imaging to achieve precise guidance for cancer therapy. This work provides a feasible way in designing new oxygenation nanomaterials to relieve tumor hypoxia for enhanced cancer treatment.

Metal-organic framework

Two-photon

Hypoxia

Sonodynamic therapy

Photodynamic therapy.

As the second leading cause of human death, cancer poses a grievous threat to human health [1, 2]. Facing the characteristics of infinite proliferation and easy metastasis of tumor cells, traditional radiotherapy and chemotherapy in combating cancer cells show unsatisfactory treatment results due to the multidrug resistance and severe side effects [3-5]. In this sense, researchers have made great efforts to develop more effective treatment methods, such as sonodynamic therapy (SDT) and photodynamic therapy (PDT), which are noninvasive tools with high selectivity for local cancers given the generated reactive oxygen species (ROS) from the photo/sonosensitizers by laser/ultrasound irradiation in an aerobic environment [6-8]. Unfortunately, the hypoxic environment of the tumor significantly limits their efficiencies [9-12]. To this end, it is imperative to develop a valid PDT/SDT system that can relieve tumor hypoxia.

Presently, the PDT agents used in clinic are mainly porphyrin derivatives, the excitation wavelength of which are located in the visible region (400-700 nm) leads to poor penetration limiting their further application [13, 14]. However, it is worth mentioning that these porphyrin derivatives can be employed as sonosensitizers to effectively compensate for the barrier of shallow penetration depth in PDT [15, 16]. Notably, the above two cancer treatment methods are highly oxygen dependent, the severe hypoxic environment of tumor greatly limits the corresponding outcome [17-20]. To face this grand challenge, various solutions have been developed to fabricate new oxygenation nanomaterials [21-23]. Among of them, the introduction of oxygen-generating units triggered by Fenton/Fenton-like reaction was recognized to be one of the most promising approach [24-26]. Therefore, the search for platforms involving Fenton/Fenton-like reaction based on porphyrin derivatives, which can relieve tumor hypoxia via oxygen-generating strategy, to achieve enhanced therapy outcome is a extraordinary desired target.

Based on the above considerations, we fabricated a porphyrinic MOF-based nanoplatform involving Fenton-like reaction, Pd@MOF-525@HA, for enhanced oxygen-dependent anti-tumor therapy outcome. Thereinto, the porphyrinic MOF, namely MOF-525 [27], was chosen as the target support based on the following considerations: (1) The porphyrin moiety within framework can act not only as PDT and SDT agents but also as two-photon responsive unit for near infrared (NIR) light-induced PDT with deeper tissue penetration due to its large π-conjugated system and rigid planar structure [28-30]; (2) The highly dispersed Pd nanocubes can be readily encapsulated, which can react with over-expressed H₂O₂ in cancer cells to produce hydroxyl radicals (•OH) and O₂ through Fenton-like reaction and then greatly alleviates the tumor hypoxia [31, 32]; (3) The hyaluronic acid (HA)-wrapping through surface modification gives rise to considerable biocompatibility and cancer cell-specific targeting ability [33-35]. The results show that the obtained two-photon responsive nanoplatform, Pd@MOF-525@HA, possess deeper tissue penetration, considerable light/ultrasonic-induced singlet oxygen (¹O₂) generation capacity, efficient oxygen generation and cancer cell specific targeting ability. Besides, we further combined two-photon fluorescence imaging to realize the combined precision anti-cancer treatment via PDT/SDT/CDT method.

The composite Pd@MOF-525 with appropriate size for cellular uptake was constructed by introducing 5,10,15,20-tetracarboxy(4-carboxyphenyl)porphyrin (TCPP), pre-synthesized Zr₆ clusters and Pd nanocubes via in-situ growth method [36]. As shown in Fig. 1A, the morphology of obtained Pd nanocubes was observed by transmission electron microscopy (TEM), which has a regular cubic structure, uniform size (≈ 10 nm) and good monodispersity. Moreover, the lattice spacing of 0.22 nm observed in the high-resolution TEM (HRTEM) image was assigned to the Pd (111) plane, confirming the structure of Pd nanocubes [37]. The TEM and scanning electron microscopy (SEM) images displayed clearly that Pd nanocubes were dispersed within MOF-525 and the size of Pd@MOF-525 increased to 130 nm (Fig. 1B-C). Simultaneously, the TEM elemental mappings were further performed for the Pd@MOF-525 composite, which proved that the homogeneous distribution of Pd element in the MOF-525 framework (Fig. 1D and Additional file 1: Fig. S1). Besides, the fabricated MOF-525 and Pd@MOF-525 was further demonstrated by the power X-ray diffraction (PXRD). These peaks could be matched with the parent framework of MOF-525 (Fig. 1E) and the characteristic peaks of Pd nanocubes were appeared at high angles of 40.0 and 46.0 (Additional file 1: Fig. S2). In addition, HA was used to further modify the surface of Pd@MOF-525 to enhance its biocompatibility and cancer-specific targeting ability for further biological applications. The zeta potential analysis (Fig. 1F) manifested a obviously change in the surface charge from a positive potential of MOF-525 (+7.16 mV) to the negative potential of Pd@MOF-525 (-4.98 mV) and Pd@MOF-525@HA (-12 mV), corroborating the successful encapsulation of Pd and wrapping of HA. Moreover, as shown by dynamic light scattering (DLS) measurements (Fig. 1G), the average hydrodynamic diameters were reasonablely enlarged from 156 nm (MOF-525) to 173 nm (Pd@MOF-525@HA) and then to 197 nm for Pd@MOF-525@HA. All the above data results demonstrated the successful fabrication of Pd@MOF-525@HA.

The successful preparation of Pd@MOF-525@HA inspired us to further study its photophysical properties. From the absorption spectrum of Pd@MOF-525@HA (Fig. 2A), the characteristic absorption for MOF-525 could be observed. First of all, considering the large π-conjugated feature of porphyrin moiety within frameworks, we investigated the reverse saturation absorption (RSA) characteristics by z-scan experiments under near-infrared laser (800 nm) with different pulse energies (Fig. 2B) [38]. The results showed that the absorption intensity gradually enhanced with the pulse energy. Moreover, the relationship between changes of normalized (ΔT₀, the minimum value of T_NL(Z) curves) transmittance with laser pulse energy (E) was fitted in the log-log scale. As illustrated in Fig. 2C, the slope was calculated as 1.02 (the slope of the curve plus 1 is the number of effective photons absorbed) for Pd@MOF-525@HA, illustrating its two-photon absorption feature. It implies that Pd@MOF-525@HA can serve as an excellent candidate for NIR light-induced two-photon bioimaging.

Secondly, the light-induced ROS production ability of Pd@MOF-525@HA was studied systematically. As shown in Fig. 2D, the typical absorption of 9,10-anthracenediyl-bis(methylene)dimalonic acid (ABDA, ¹O₂ indicator) increased under light or ultrasonic irradiation, demonstrating the excellent ¹O₂ generation ability of Pd@MOF-525@HA. Notably, the well-dispersed Pd nanocubes within MOF-525 can convert H₂O₂ into •OH and O₂ through Fenton-like reaction and then further improving the ¹O₂ generation ability of Pd@MOF-525@HA (Fig. 2E). Meanwhile, the oxygen production capacity of Pd@MOF-525@HA was measured by the dissolved oxygen meter to determine the concentration of O₂ in the solution (Fig. 2F). It was found that the O₂ concentration continued to increase after 15 minutes of repeated addition of H₂O₂, indicating that Pd@MOF-525@HA can continuously catalyze H₂O₂ to produce O₂. On the other hand, the ROS fluorescent probe 2',7'-dichlorofluorescein diacetate (DCFH-DA) is used to detect •OH under dark condition (Fig. 2G). The emission spectrum of DCFH-DA increased significantly after adding H₂O₂, which proved its excellent catalytic capacity of •OH production through Fenton-like reaction. Moreover, electron spin resonance trapping measurements using 5,5-dimethyl-1-pyrro-Line-N-oxide (DMPO) and 2,2,6,6-tetramethylpiperidine (TEMP) as the capture agent were further carried out to verify the type of produced ROS. The typical signal of DMPO-OOH (1:2:2:1 triplet) was observed after adding H₂O₂ into Pd@MOF-525@HA, indicating the production of •OH (Fig. 2H). In addition, the characteristic signals of 4-oxo-TEMPO (1:1:1 triplet) for Pd@MOF-525@HA was acquired under laser and ultrasonic irradiation, manifesting the production of ¹O₂ (Fig. 2I). In this sense, Pd@MOF-525@HA provides the possibility to relieve tumor hypoxia via oxygen-generating strategy for enhanced oxygen-dependent anti-tumor therapy.

Encouraged by the two-photon feature and HA-wrapping Pd@MOF-525@HA, cellular uptake experiments with CD44 negative cells of human liver cells (QSG-7701) and CD44 positive cells of human liver cancer cell (tumor cells HepG2) were performed to evaluate its tumor cell-specific targeting and NIR light-induced fluorescence imaging ability. As shown in Fig. 3A-B, in comparison to the weak fluorescence of QSG-7701 cells incubated with Pd@MOF-525@HA under 800 nm laser irradiation, HepG2 cells group exhibited strong fluorescence. Moreover, the weak fluorescence of HepG2 cells pre-incubated with HA attribute to the preoccupation of receptor sites of CD44 cells by free HA (Additional file 1: Fig. S3) clearly demonstrated that HA-modified Pd@MOF-525 can effectively target tumor cells with CD44 receptors resulting in two-photon fluorescence imaging.Whereafter, the cytotoxicity of Pd@MOF-525@HA under different conditions was further researched by standard (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. As shown in Fig. 3C-D, the cell viability of QSG-7701 cells treated by Pd@MOF-525@HA was higher than that of HepG2 cells groups with/without H₂O₂ addition demonstrating that Pd@MOF-525@HA was harmless to normal cells and the generated •OH via Fenton-like reaction could give rise to decreased cell survival rate. As revealed by Fig. 3E-H, obviously cell apoptosis could be observed upon the light and ultrasound irradiation, and the cell viability was further decreased upon H₂O₂ added due to the production of O₂. Notably, in the presence of H₂O₂, the survival rate of the cells treated by light and ultrasound irradiation was only 10%, which demonstrated the excellent in vitro PDT/SDT synergistic therapeutic outcome.

The in vitro PDT/SDT therapeutic effect was further evaluated through confocal laser scanning microscopy (CLSM) imaging. Firstly, the intracellular ¹O₂ and •OH generated from Pd@MOF-525@HA were detected by singlet oxygen sensor green (SOSG) and aminophenyl fluorescein (APF), respectively. As shown in Fig. 4A, obviously SOSG green fluorescence signal was collected with light/ultrasonic irradiation. Moreover, the enhanced SOSG signal from light and ultrasound worked together could be further improved when H₂O₂ added, which further unveiled that the light/ultrasonic induced ¹O₂ generation ability of Pd@MOF-525@HA could be effectively boosted by O₂ production from Fenton-like reaction. Simultaneously, the obvious green fluorescence of APF was observed due to the generation of •OH (Fig. 4B) and the enhanced APF signal from H₂O₂ addition could be effectively quenched after adding •OH scavenger (ascorbic acid, AA). The above results corroborated the ROS generation ability of Pd@MOF-525@HA in cells for further treatment application. In addition, as demonstrated by the 3D fluorescence images collected by one- and two-photon fluorescence imaging of fixed mouse brain tissue (Fig. 4C-D), the deeper penetration depth (60 µm) of Pd@MOF-525@HA upon 800 nm laser irradiation provided a promising platform for improved therapy outcome guided by two-photon fluorescence imaging.

Based on the deep tissue penetration and excellent intracellular ROS generation of Pd@MOF-525@HA, we deployed a thoughtful protocol to evaluate the efficacy of in vitro PDT/SDT therapy. The apoptosis was detected by using Calcein acetoxymethyl ester (Calcein AM, green) and propidium iodide (PI, red). As shown in Fig. 5A, brighter PI signal was collected when light and ultrasound worked together than that of only light or ultrasound treatment groups. Moreover, much brighter PI signal could be observed upon H₂O₂ addition demonstrating the enhanced in vitro PDT and SDT effect by alleviating hypoxia environment. The above results were further confirmed by Annexin V-FITC/PI treatment assay (Fig. 5B). In addition, the cell apoptosis was analyzed by flow cytometry using annexin V-FITC and PI as indicators under different treatment conditions. Upon light (800 nm, 100 mW cm⁻²) and ultrasound (100 mW cm⁻²) irradiation for 15 minutes, the fraction of late apoptotic cells was 56.68%, which was higher than that of only light (41.99%) or ultrasound (30.82%) treatment group (Fig. 5C). With the addition of H₂O₂, the late apoptotic cells reached 87.73% suggesting enhanced oxygen-dependent therapeutic effect due to the generation of O₂. Furthermore, HepG2 3D multicellular tumor spheroids of 3D cancer model (3D MCTs) were incubated with Pd@MOF-525@HA and stained with Calcein AM/PI to validate the efficiency in deep tissue. As shown in Fig. 5D, in contrast to the faint red fluorescence of control group, MCTs formed an obvious necrotic core with bright PI fluorescence upon the NIR light and ultrasound irradiation corroborating the outstanding synergistic therapeutic effect. It manifested that Pd@MOF-525@HA can be employed as a PDT and SDT combination therapy platform guided by two-photon fluorescence imaging.

In summary, an intelligent nanoplatform (Pd@MOF-525@HA) involving Fenton-like reaction was fabricated for enhanced oxygen-dependent anti-tumor therapy by oxygen-generating strategy. Thanks to the successful synthesis of the porphyrinic metal-organic framework, it can act not only as photo/sonosensitizers but also as two-photon responsive unit, the excellent ¹O₂ generation ability leads to considerable PDT and SDT outcome with deeper tissue penetration. In addition, the therapy effect can be further enhanced due to the O₂ production from Pd nanocubes through Fenton-like reaction. It provides a promising platform to relieve tumor hypoxia via oxygen-generating strategy for enhanced oxygen-dependent anti-tumor therapy.

Materials

All starting materials were obtained from commercial supplies and used without further purification. The chemicals of Sodium tetrachloropalladate(II) (Na₂PdCl₄), Sodium bromide (NaBr), 2′,7′-dichlorofluorescein diacetate (DCFH-DA), Ascorbic acid (AA) and Hyaluronic acid (HA) were purchased from Macklin Co., Ltd. The chemicals of acetone, polyvinylpyrrolidone (PVP, 58000w), N,N-Dimethylformamide (DMF), Ethanol and Acetic acid from Aladdin Co., Ltd. (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) was obtained from Beyotime Biotech Co., Ltd. (China). Calcein AM/PI Kit and Annexin V-FITC/PI Apoptosis Detection Kit was obtained from Shanghai Bestbio (China). Ultrapure water was used throughout.

Synthesis Of Pd Nanocubes

PVP (53 mg), AA (30 mg), NaBr (130 mg) were dissolved into ultrapure water (4 mL), the mixture was then stirred at 80 ℃ over 5 minutes. 30 mg of Na₂PdCl₄ (dissolved in 1.5 mL of ultrapure water) was poured in the above mixture and stirred for 3 hours. After been cooled to room temperature, Pd nanocubes were collected by centrifugation and then stored it in 1mL of DMF solution.

Synthesis Of Pd@mof-525

3 mL of the synthesized Pd nanocubes were added to 2 mL DMF solution containing 100 mg Zr₆ clusters), then the solution was stirred at room temperature for 4 hours (solution A). TCPP (50 mg) was then dissolved into DMF solution (5 mL) and dispersed by ultrasound (solution B). Then acetic acid (6 mL) was added to mixed mixture of solution A and solution B, and stirred for 12 hours. Finally, the product was collected after centrifugation and washing.

Synthesis Of Pd@mof-525@ha

HA (10 mg) was dispersed in the ultrapure water (100 mL), 5 mg of Pd@MOF-525 was added after ultrasonic. After stirring for 24 hours, washed with ultrapure water, and the final product was stored in ultrapure water.

Apparatus

UV-Vis absorption spectra were recorded on a UV-265 spectrophotometer. SEM was detected by REGULUS8230*. TEM was carried on a JEM-2100. PXRD patterns were recorded on SmartLab 9KW. Fluorescence measurements were performed on a Hitachi F-7000 fluorescence spectrophotometer. One-photon and two-photon imaging data acquisition and processing were performed using Lecia TCS SP8 DIVE FALCON which equipped with single-wavelength laser and femtosecond laser (adjustable output wavelength: 680 - 1080 nm, 80 MHz, 140 fs).

Singlet Oxygen (O) Detection

The ¹O₂ was detected by 9,10-anthracenedipropanoic acid (ABDA, a singlet oxygen sensor) due to the generated ¹O₂ would react with ABDA and reduce the absorbance around 378 nm. Pd@MOF-525@HA (50 µg mL⁻¹), ABDA (100 µM) and H₂O₂ (100 µM) were incubated together under white light and ultrasound (1.2 W cm⁻²) irradiation within 0-5 minutes. The absorbance of the mixture was measured at the different time.

Electron Spin Resonance (Esr) Assay

The spin traps 2,2,6,6-tetramethylpiperidine (TEMP, trapping ¹O₂, 20 µL) and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO, trapping •OH, 20 µL) were employed to detect the species of ROS generated by Pd@MOF-525@HA (50 µg mL⁻¹). The ESR signals of the Pd@MOF-525@HA before and after LED light (range from 400 to 700 nm, 40 mW cm⁻²) and ultrasound (1.2 W cm⁻²) irradiation were recorded.

Cellular Uptake Analysis

QSG-7701 cells (CD44-negative) and HepG2 cells (CD44-positive) were seeded onto the cell culture dishes and grown to about 70% confluency for next using. QSG-7701 cells and HepG2 cells were treated with Pd@MOF-525@HA (100 µg mL⁻¹, and another dish HepG2 cells were precultured with 10 times of HA before incubation with Pd@MOF-525@HA. And after 8 hours of incubation, the cellular uptake ability of Pd@MOF-525@HA were analyzed using CLSM.

Cytotoxicity Assays In Cells

The PDT/CDT/SDT effect of Pd@MOF-525@HA was studied by the methylthiazolyldiphenyltetrazolium bromide (MTT) assay. The Pd@MOF-525@HA stock solution is diluted with fresh medium to the required concentration (0, 30, 60, 90, 120, 150 µg mL⁻¹). Before the experiment, HepG2 cells were cultured for 24 hours in 96-well plates. Then exchange the cell culture medium with different concentrations of Pd@MOF-525@HA medium solution. They were incubated at 37°C for 8 hours in 5% CO₂ atmosphere, and then irradiated by laser (800 nm, 1 W cm⁻²) and ultrasound (1.2 W cm⁻²) for 15 min. 100 µL of fresh medium were used to exchange the cell medium solutions 20 µL (5 mg mL⁻¹) MTT solution were added to each well following. The cell plates were then incubated for another 4 hours. After removing the MTT medium, the formazan crystals were dissolved in DMSO (100 µL well⁻¹) and the absorbance was detected at 490 nm using a microplate reader. And duplicated experiments have been tested.

Singlet Oxygen Detection In Cells

HepG2 cells were treated with Pd@MOF-525@HA (100 µg mL⁻¹) for 8 hours, and then incubated with 1 µM singlet oxygen sensor green (SOSG) for 10 minutes. Next, HepG2 cells were washed with PBS and irradiated for 15 minutes under laser (800 nm, 1 W cm⁻²) and ultrasound (1.2 W cm⁻²). The green fluorescence was observed by CLSM with the excitation wavelength of 504 nm (λ_em: 500-550nm).

Live/dead Assay With Calcein Am/pi

After the HepG2 cells were washed with PBS solution twice, Pd@MOF-525@HA (100 µg mL⁻¹) was added to the above medium and incubated for 8 hours, and then the cells were treated under different conditions. Calcein AM and PI were added to detect the cells vitality of HepG2 cells. Fluorescence images are collected by CLSM.

Determination Of Annexin V-fitc And Pi

HepG2 cells were incubated with Pd@MOF-525@HA (100 µg mL⁻¹) at 35°C and 5% CO₂ for 8 hours. After adding H₂O₂, they were irradiated with laser (800 nm, 1 W cm⁻²) and ultrasound (1.2 W cm⁻²) for 15 minutes. Then, the Annexin V-FITC (1 µM) and PI (1 µM) were added and incubated for 20 minutes. Fluorescence images of the cells were collected by a confocal laser scanning microscope.

Flow Cytometry Study

Cells seeded into the 6-well plates were incubated for 24 hours, the medium containing Pd@MOF-525@HA (100 µg mL⁻¹) was used.. After irradiated with laser (800 nm, 1W cm⁻²) and ultrasound (1.2 W cm⁻²) 15 minutes, the cells were collected after centrifugation and then resuspended in binding buffer containing Propidium Iodide (PI, 10 µL) and Annexin-V FITC (5 µL) for 15 minutes in darkness. The signal was collected by a BD FACS Calibur flow cytometer (Beckaman/Gallios).

The One/two-photon Fluorescence Imaging Study Of Pd@mof-525@ha

A Lecia TCS SP8 DIVE FALCON which equipped with single-wavelength laser and femtosecond laser (adjustable output wavelength: 680 - 1080 nm, 80 MHz, 140 fs) was employed to achieve one/two-photon fluorescence imaging. HepG2 cells were treated with Pd@MOF-525@HA for 8 hours. And then, slices were prepared from cardiac muscle tissue in Balb/c mice. The tissue sections were cut to 200 mm thickness. The tissue sections was incubated with Pd@MOF-525@HA for 30 minutes. The one-photon fluorescence emission was observed excitation at 458 nm (0.2 W/cm²). The two-photon fluorescence emission was observed excitation at 800 nm (0.2 W/cm²).

¹O₂: singlet oxygen; PDT: photodynamic therapy; SDT: sonodynamic therapy; NIR: near infrared; ROS: reactive oxygen species; •OH: hydroxyl radicals; RSA: reverse saturation absorption;

Acknowledgements

We appreciate the support form National Natural Science Foundation of China (22171001 and 21701160) and Natural Science Foundation of Anhui Province of China(2108085MB49).

Authors’ contributions

WenyaoDuan: Investigation, Data curation, Writing-original draft. Bo Li: Investigation, Software, Formal analysis. Wen Zhang: Investigation, Methodology.Jiaqi Li: Investigation, Methodology. Xin Yao: Investigation, Methodology. Yupeng Tian: Re- sources,Formalanalysis. JunZheng: Conceptualization, Methodology, Supervision. Dandan Li: Conceptualization, Methodology, Writing-review & editing, Supervision.

Funding

This work was supported by a grant for the National Natural Science Foundation of China (21701160), Doctor Startup Fund (S020118002/026 and S020118002/073), Natural Science Foundation of Anhui Province of China (1908085MB30).

Availability of data and materials

All data generated or analyzed during this study are included in this publishedarticle and its additional files.

Competing interests

There are no conflicts to declare.

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You are reading this latest preprint version

Two-Photon Responsive Porphyrinic Metal-Organic Framework Involving Fenton-Like Reaction for Enhanced Photodynamic and Sonodynamic Therapy

Status:

Version 1

Abstract

Figures

Introduction

Results And Discussion

Conclusion

Materials And Methods

Materials

Synthesis Of Pd Nanocubes

Synthesis Of Pd@mof-525

Synthesis Of Pd@mof-525@ha

Apparatus

Singlet Oxygen (O) Detection

Electron Spin Resonance (Esr) Assay

Cellular Uptake Analysis

Cytotoxicity Assays In Cells

Singlet Oxygen Detection In Cells

Live/dead Assay With Calcein Am/pi

Determination Of Annexin V-fitc And Pi

Flow Cytometry Study

The One/two-photon Fluorescence Imaging Study Of Pd@mof-525@ha

Abbreviations

Declarations

References

Supplementary Files

Status:

Version 1