Photodynamic Agents Research Articles

Cellular Hypoxia Mitigation by Dandelion-like Nanoparticles for Synergistic Photodynamic Therapy of Oral Squamous Cell Carcinoma.

Hypoxia at the tumor site limits the therapeutic effects of photodynamic therapy (PDT) in oral squamous cell carcinoma (OSCC), which is an oxygen-consumption process. Inhibiting cellular oxygen consumption and reducing cellular ATP production are expected to enhance PDT. In this study, we designed and constructed dandelion-like size-shrinkable nanoparticles for tumor-targeted delivery of hypoxia regulator resveratrol (RES) and photodynamic agent chlorine e6 (CE6). Both drugs were co-encapsulated in small-sized micelles modified with EGFR targeting ligand GE11, which was further conjugated on hyaluronic nanogel (NG) to afford RC-GMN. After targeted accumulation in tumors mediated by GE11 and enhanced penetration and retention (EPR) effects, RC-GMN was degraded by hyaluronidase (HAase) and resulted in small-sized micelles, allowing for deep penetration and dual-receptor-mediated cellular internalization. Resveratrol inhibited cellular oxygen consumption and provided sufficient oxygen for PDT, which consequently activated PDT to produce reactive oxygen species (ROS). Notably, we found that autophagy was overactivated in PDT, which was further strengthened by the hypoxia regulator resveratrol, elevating autophagic cell death. The synergistic effects of resveratrol and CE6 promoted autophagic cell death and apoptosis in the enhanced PDT, resulting in stronger antitumor effects in the orthotopic OSCC model. Therefore, the facilitated delivery of hypoxia regulator enhanced PDT efficacy by elevating oxygen content in tumor cells and inducing autophagic cell death and apoptosis, which offers an alternative strategy for enhancing the PDT effects against OSCC.

Albumin microbubbles conjugated with zinc and aluminum phthalocyanine dyes for enhanced photodynamic activity

Gas-liquid interfaces are reaching a particular interest in biomedicine. Microbubbles, ultrasound contrast agents of clinical routine, gained increasing attention as theranostic platforms due to the preserved acoustic response, drug conjugation capabilities, and applicability in biological barrier opening. A combination of microbubbles and photodynamic therapy agents can enhance the photodynamic effect, yet the evaluation of agent conjugation on microbubble stabilization and photodynamic effect is needed. Hence, two commercially available phthalocyanine photosensitizers — Holosens® (ZnPc) and Photosens® (AlPc) — were coupled with bovine serum albumin before microbubble synthesis. We demonstrated an albumin: phthalocyanine ratio of 1:1 and covalent attachment for ZnPc, a ratio of 1:3 with electrostatic binding for AlPc. Submicron-sized microbubbles (air- and SF6- filled) had a diameter of 0.8 µm. Albumin-phthalocyanine conjugates increased the microbubble concentration and shelf-life stability compared to plain ones. We hypothesized that phthalocyanine fluorescence lifetime values decreased after conjugation with microbubbles due to narrow distance between conjugates in the shell. Agents based on AlPc demonstrated higher photodynamic activity than agents based on ZnPc, and microbubbles preserved acoustic stability in human blood plasma. The biodistribution of AlPc-conjugated microbubbles was evaluated. We conclude that our microbubble platforms demonstrate greater photodynamic activity and prolonged stability for further applications in photodynamic therapy.

Locked and Loaded: β-Galactosidase Activated Photodynamic Therapy Agent Enables Selective Imaging and Targeted Treatment of Glioblastoma Multiforme Cancer Cells.

Selective detection and effective therapy of brain cancer, specifically, the very aggressive glioblastoma multiforme (GBM), remains one of the paramount challenges in clinical settings. While radiotherapy combined surgery is proposed as the main treatment course, it has several drawbacks such as complexity of the operation and common development of recurrent tumors in this course of patient care. Unique opportunities presented by photodynamic therapy (PDT) offer promising, effective, and precise therapy against GBM cells along with simultaneous imaging opportunities. However, activatable, theranostic molecular systems in PDT modality for GBM remained scarce. Specifically, even though elevated β-galactosidase (β-gal) activity in glioblastoma cells is well-documented, targeted, activatable therapeutic PDT agents have not been realized. Herein, we report a β-galactosidase (β-gal) activatable phototheranostic agent based on an iodinated resorufin core (RB-1) which was realized in only three steps with commercial reagents in 29% overall yield. RB-1 showed very high singlet oxygen (1O2) quantum yield (54%) accompanied by a remarkable turn-on response in fluorescence upon enzymatic activation. RB-1 was tested in different cell lines and revealed selective photocytotoxicity in U-87MG glioblastoma cells. Additionally, thanks to almost 7% fluorescence quantum yield (ΦF) despite extremely high 1O2 generation yield, RB-1 was also demonstrated as a successful agent for fluorescence imaging of U-87MG cells. Due to significantly lower (β-gal) activity in healthy cells (NIH/3T3), RB-1 stayed in a passive state and showed minimal photo and dark toxicity. RB-1 marks the first example of a β-gal activatable phototheranostic agent toward effective treatment of glioblastoma.

The antibacterial activity of photodynamic agents against multidrug resistant bacteria causing wound infection

Antimicrobial photodynamic inactivation (aPDI) of multidrug-resistant (MDR) wound pathogens was evaluated with cationic porphyrin derivatives (CPDs). MDR bacterial strains including Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, and Klebsiella pneumoniae were used. The CPDs named PM, PE, PN, and PL were synthesized as a photosensitizer (PS). A diode laser with a wavelength of 655 nm was used as a light source. aPDI of the combinations formed with different energy densities (50, 100, and 150 J/cm²) and PS concentrations (ranging from 3.125 to 600 µM) were evaluated on each bacterial strain. Dark toxicity, cytotoxicity, and phototoxicity were determined on fibroblast cells. In the aPDI groups, survival reductions of up to 5.80 log₁₀ for E. coli, 5.90 log₁₀ for P. aeruginosa, 6.11 log₁₀ for K. pneumoniae, and 6.78 log₁₀ for A. baumannii were obtained. The cytotoxic effect of PL and PM on fibroblast cells was very limited. PN was the type of CPD with the highest dark toxicity on fibroblast cells. In terms of providing broad-spectrum aPDI without or with very limited cytotoxic effect, the best result was observed in aPDI application with PL. The other CPDs need some modifications to show bacterial selectivity for use at 50 µM and above.

Supramolecular Organic Frameworks: Exploring Water-Soluble, Regular Nanopores for Biomedical Applications.

In past decades, regular porous architectures have received a great amount of attention because of their versatile functions and applications derived from their efficient adsorption of various guests. However, most reported porous architectures exist only in the solid state. Therefore, their applications as biomaterials may face several challenges, such as phase separation, slow degradation, and long-term accumulation in the body. This Account summarizes our efforts with respect to the development and biomedical applications of water-soluble 3D diamondoid supramolecular organic frameworks (dSOFs), a family of supramolecular polymers that possess intrinsic regular nanoscale porosity.dSOFs have been constructed from tetratopic components and cucurbit[8]uril (CB[8]) through hydrophobically driven encapsulation by CB[8] for intermolecular dimers formed by peripheral aromatic subunits of the tetratopic components in water. All dSOFs exhibit porosity regularity or periodicity in aqueous solution, which is confirmed by solution-phase synchrotron SAXS and XRD experiments. Dynamic light scattering (DLS) reveals that their sizes range from 50 to 150 nm, depending on the concentrations of the components. As nonequilibrium supramolecular architectures, dSOFs can maintain their nanoscale sizes at micromolar concentrations for dozens of hours. Their diamondoid pores have aperture sizes ranging from 2.1 to 3.6 nm, whereas their water solubility and porosity regularity allow them to rapidly include discrete guests driven by ion-pair electrostatic attraction, hydrophobicity, or a combination of the two interactions. The guests may be small molecule or large macromolecular drugs, photodynamic agents (PDAs), or DNA.The rapid inclusion of bioactive guests into dSOFs has led to two important biofunctions. The first is to function as antidotes through including residual drugs. For heparins, the inclusion results in full neutralization of their anticoagulant activity. For clinically used porphyrin PDAs, the inclusion can alleviate their long-term posttreatment phototoxicity but does not reduce their photodynamic efficacy. The second is to function as in situ loading carriers for the intracellular delivery of antitumor drugs or DNA. Their nanoscale sizes bring out their ability to overcome the multidrug resistance of tumor cells, which leads to a remarkable enhancement of the bioactivity of the included drugs. By conjugating aldoxorubicin to tetrahedral components, albumin-mimicking prodrugs have also been constructed, which conspicuously improves the efficacy of aldoxorubicin toward multi-drug-resistant tumors through the delivery of the frameworks. As new supramolecular drugs and carriers, dSOFs are generally biocompatible. Thus, further efforts might lead to medical benefits in the future.

Effect of the phenyl substituent’s position on the encapsulation of porphyrins inside lignin nanoparticles: Photophysical and antibacterial properties

Porphyrins are well studied molecules that are widely used in Photodynamic Therapy, aiming for the eradication of tumours, but also for the eradication of bacteria. The formulation of porphyrins is a crucial factor when developing photodynamic applications, due to the limited stability and low solubility of porphyrins in aqueous media. Our research group has previously demonstrated that porphyrins, and especially 5,10,15,20-tetrakis(4-hydroxyphenyl)porphyrin are easily encapsulated inside acetylated lignin spherical nanoparticles, while conserving their main photophysical features. In the present study we encapsulated 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin, the precursor of the well-known photosensitizer Temoporfin, in acetylated lignin nanoparticles, yielding a stable formulation while keeping the photophysical properties of the encapsulated porphyrin. This formulation was tested as a photodynamic antibacterial agent against Staphylococcus aureus CIP 76.25 and Escherichia coli CIP 53.126, where it efficiently eradicated S. aureus, although also showing non-neglectable dark toxicity against the bacterial cells. In conclusion, the 3-hydroxyphenyl substituted porphyrin yielded nanoparticles physically and photophysically similar to those prepared with its isomer. However, the change in the position of the phenyl substituent seems to increase the dark toxicity of the nanoparticles, a phenomenon that still needs to be explored.

Porous organic polymer overcomes the post-treatment phototoxicity of photodynamic agents and maintains their antitumor efficiency

Since 1995, photodynamic therapy (PDT) has been utilized as an effective method for cancer treatment. However, the residues of photosensitizers in the normal tissues after PDT can be activated by sunlight to cause severe skin phototoxicity, for which currently there are no clinical solutions. As a result, post-PDT patients need to remain out of sunlight for up to five weeks, which produces great living and mental burdens for patients. Herein, we report that a biocompatible porous organic polymer (POP) with average 3.1 nm porosity is able to suppress the skin phototoxicity of clinically used porphyrin-based photodynamic agents (PDAs), including Photofrin, Talaporfin and Hiporfin, through an adsorption-elimination mechanism. Fluorescence titration and dialysis experiments show that POP can adsorb and retain the PDAs at a micromolar concentration. In vivo experiments demonstrate that POP can significantly suppress the skin phototoxicity caused by all the three PDAs without reducing their PDT efficacy. Statement of significanceUp to now, no efficient clinical treatment for the inhibition of post-PDT phototoxicity of clinically used porphyrin-based PDAs is available. In the manuscript, a water-soluble cationic porous organic polymer has been revealed to include three clinically used PDAs. In vivo experiments show that this inclusion remarkably reduces the content of PDAs in mouse skins, leading to significant alleviation of their post-PDT phototoxicity without no negative effect on their PDT efficacy. Thus, this work provides a strategy for overcoming the drawback of clinically used photodynamic agents.

Neovascularization-directed bionic eye drops for noninvasive renovation of age-related macular degeneration

The current treatment of wet age-related macular degeneration (wAMD) relies on monthly intravitreal or intravenously injection of vascular endothelial growth factor (VEGF) inhibitor or photodynamic (PDT) agents to inhibit choroidal neovascularization. However, traumatic local therapy and exogenous long-distance fundus drug delivery often lead to secondary eye damage, low treatment efficiency, and immunogenic inflammation. Herein, inspired by the natural neovascular targeting ability of endogenous low-density lipoproteins (LDL), a noninvasive bionic nano-eye-drop with enhanced ocular penetrability and lesion recognizability is developed for enabling the PDT treatment of wAMD. Verteporfin (VP) as a laser-induced PDT agent is protected inside the hydrophobic core of reconstituted LDL (rLDL) vectors. 5-carboxyfluorescein (FAM) conjugated ste-penetratin (PEN, a transmembrane peptide) is anchored on the surface of the rLDL carrier, which enabled the nanoparticles (PEN-rLDL-VP) to cross the blood-retina barrier to realizing visual therapy. Following instillation, PEN-rLDL-VP can effectively deliver VP into neovascular that overexpress LDL receptors, which can respond to laser-induced PDT. Only with a single dose of the eye-drop and laser-induced PDT, the VEGF and proinflammatory intercellular adhesion molecule-1 (ICAM-1) proteins are significantly down-regulated in vivo, which implicates the neovascular inhibition and inflammation alleviation. This study presents an attractive non-invasive strategy for the PDT of wAMD.

Microwave-assisted synthesis and photodynamic activity of tris-heteroleptic Ru(II) complexes with asymmetric polypyridyl ligands

Ru(II) polypyridyl complexes are attracting particular attention as possible photodynamic therapy (PDT) agents due to their interesting photophysical properties, which can be easily tunable through the appropriate selection of attached ligands. However, blue-wavelength absorption of the complexes limited their potential application. In this study, three tris-heteroleptic Ru(II) polypyridyl complexes were synthesized to shift the absorption of the compounds toward longer wavelengths. Their photophysical, biological, and photodynamic properties were evaluated. The mechanism of the photoinduced toxicity was investigated by fluorescence and electron paramagnetic resonance (EPR) techniques in vitro and in aqueous solutions. The results revealed the photodynamic activity of the studied compounds is based mainly on the photogeneration of 1O2 and H2O2. Additionally, the synthesized Ru complexes demonstrated high activity in inhibiting the detachment of cancer cells. This effect was additionally enhanced by light activation of Ru compounds. The presented findings demonstrate a rational strategy for the efficient synthesis of tris-heteroleptic Ru(II) polypyridyl complexes to be used as promising photodynamic agents for cancer and antimetastatic treatments.

NRNC-8, a novel mitochondria-immobilization superoxide radical generator for photodynamic therapy

Mitochondria play an important role in carcinogenesis, and alterations in mitochondrial activity are frequently associated with cancer formation. Mitochondria have become attractive targets for cancer therapy, with mitochondria-targeted photodynamic therapy (PDT) being one of the most prominent fields. However, significant limitations remain, such as low spectroscopic absorption, short photosensitizer absorption wavelengths, and organelle targeting stability deterioration during phototherapy. In this work, we synthesized an Aza-Nile red-structured near-infrared photosensitizer NRNC-8 based on side-chain engineering for the first time. NRNC-8 can be successfully immobilized on mitochondria in a reaction-free way by linking C8 alkyl chain on the N atom. This reaction-free immobilization approach efficiently prevents irreversible damage to mitochondrial structure and potential effects on mitochondrial function, as well as photosensitizer leaking from mitochondria during phototherapy. Superoxide anion (O2•-) can be created efficiently under red LED irradiation, which directly damages mitochondria and causes cell death, boosting PDT efficiency. A series of studies demonstrated the great potential of NRNC-8 dyes as efficient mitochondria-targeted imaging-guided photodynamic therapy agents, further highlighting the potential value of the “reaction-free mitochondrion-immobilized” strategy in the design of mitochondria-targeted photosensitizers for more efficient photodynamic therapy.

Synthesis, characterization, DNA photocleavage, in silico and in vitro DNA/BSA binding properties of novel hexahydroquinolines

A simple, and efficient procedure has been developed for the synthesis of novel 2-(4-(hexahydroquinolin-4-yl)phenoxy)-N-arylacetamides and thieno[3′,2′:5,6]pyrimido[1,2-a]quinolines via Michael addition reaction of cyclic enaminones with various 2-(4-(2,2-dicyanovinyl)phenoxy)-N-arylacetamides in the presence of a basic catalyst. The interaction of the compounds with DNA and bovine serum albumin (BSA) was investigated. DNA photocleavage ability was evaluated by agarose gel electrophoresis in UV-A (356 nm). Through inhibitor studies of the most active compounds 5h and 12d, we found that reactive oxygen species play a major role in photocleavage. Molecular docking methods were also used to model the binding of the compound to DNA and BSA, and good agreement was found between experimental and theoretical results. All of these findings suggest that the compounds could be used as a photodynamic therapy agent due to their nucleic acid interactions and photobiological or photochemical properties.

Photodynamic anti-inflammatory activity of azulene derivatives on mammalian macrophages and their intracellular mechanism of action

Azulene derivatives have been studied previously as photodynamic therapy agents. They have anti-cancer, anti-microbial and anti-inflammatory activities. Together with their photodynamic activity they enable more control on their activation which aims to decrease possible side effects that have been encountered with their constitutively active drug counterparts. In our current study we focused on photodynamic anti-inflammatory activities of two azulene derivatives whose synthesis methods were described before. We found that when mammalian macrophages J774.2 cells were incubated with these two derivatives in the presence of LPS in dark conditions, these molecules had anti-inflammatory activity at their highest concentrations based on ELISA results on the pro-inflammatory cytokine levels. After light application, both derivatives exerted strong anti-inflammatory activities by substantially decreasing the TNF, IL6, GMCSF and IL12p40 cytokine production levels. When the intracellular mechanism of action for both derivatives was tested, only one of them acted through p38 and PI3K pathways whereas the other derivative did not affect either of these pathways. Our results suggest that these two azulene derivatives can be utilized as photodynamic anti-inflammatory drug candidates.

Evaluation of silver nanoparticles attached to methylene blue as an antimicrobial agent and its cytotoxicity

Antibiotic resistance is a great public health challenge of our time. In this work, we have synthesized silver nanoparticles (Ag NPs) using pulsed liquid ablation in different medium of growth and later combined with methylene blue (MB) to evaluate its potential as an effective photodynamic therapy agent. Ag NPs were synthesized by pulsed laser ablation technique in Polyvinylpyrrolidone (PVP), citrate, and Polyvinyl alcohol (PVA). The Ag NPs were characterized using transmission electron microscopy (TEM), UV-Visible (UV-Vis), and photoluminescence (PL) spectra. Next, Ag NPs were coupled with MB and used to deactivate the Gram-negative bacteria, Escherichia coli (E. coli), and Gram-positive bacteria, Staphylococcus aureus (S. aureus). MB and Ag NPs mixture exhibited a synergistic activity and was more effective compared to separate use of MB and Ag NPs. Ag NPs in PVP was shown to be the most effective media for bacterial deactivation. Given the concern for Ag NPs’ cytotoxicity for adverse health effect, cytotoxicity measurement in HEK 293T cell lines were performed. Our results show that Ag NPs do not exhibit cytotoxicity up to 50 µg/ml in each solution. Ag NPs/ MB combination has potential to be used in PDT where standard photosensitizers have limitations.

Effect of laser ablated gold nanoparticles on the nonlinear optical properties of π-extended BODIPY dyes

Dipyrromethene boron difluoride (BODIPY) and its derivatives have attracted considerable interest due to their remarkable photophysical properties beneficial for developing fluorescent sensors, biolabels, photodynamic therapy agents, photonic materials, and so on. Herein, we report gold nanoparticles (AuNPs) induced modulation of nonlinear optical properties of π-extended BODIPY derivatives BPA and BDIPA. The spherical gold nanoparticles with an average particle size of 11 ± 3.5 nm were synthesized by pulsed laser ablation technique and characterized by transmission electron microscopy and dynamic light scattering. The interaction of AuNPs with the dye molecules was confirmed by UV/vis absorption and steady-state emission spectroscopy studies. Further, the dual-beam thermal lens technique was used to validate dye-nanoparticle interaction. The thermal diffusivity values of the samples at an excitation wavelength of 532 nm were measured and found that the overall heat diffusion was slower in the AuNPs added samples than that of the dye alone sample, corroborating dye-nanoparticle interaction. The third-order nonlinear optical absorption properties of the samples were investigated by using the Z-scan technique in the infrared region (1064 nm). The open aperture configuration shows significant reverse saturable absorption characteristics for all the samples. Determination of nonlinear absorption coefficient for the dye samples at different input intensities identified two-photon absorption as the important mechanism that produces reverse saturable absorption. The AuNPs incorporated dye samples showed a substantial enhancement in the nonlinear optical behavior. The nonlinear absorption coefficient of the AuNPs incorporated dye samples (10 cm/GW) was enhanced almost two times than that of dye alone samples (5 cm/GW). The enhanced nonlinearity is attributed to the intense local field effect of AuNPs.

Water-Based Synthesis of Copper Chalcogenide Structures and Their Photodynamic Immunomodulatory Activities on Mammalian Macrophages.

Generation of novel and versatile immunomodulatory agents that could suppress excessive inflammation has been crucial to fight against chronic inflammatory and autoimmune disorders. Immunomodulatory agents regulate the function of immune system cells to manage their activities. Current therapy regimens for the inflammatory and autoimmune disorders rely on immunomodulatory drug molecules but they are also associated with unwanted and severe side effects. In order to prevent the side effects associated with drug molecules, the field should generate novel immunomodulatory drug candidates and further test them. Moreover, the generation of photodynamic immunomodulatory molecules would also decrease possible side effects. Photodynamic activation enables specific and localized activation of the active ingredients upon exposure to a certain wavelength of light. In our study, we generated copper-based chalcogenide structures in gel and nanoparticle form by using a water-based method so that they are more biocompatible.After their chemical characterization, they were tested on mammalian macrophages in vitro. Our results suggest that these molecules were anti-inflammatory in dark conditions and their anti-inflammatory potentials significantly increased upon xenon light treatment. We are presenting novel photodynamic immunomodulatory agents that can be used to suppress excessive inflammation in disease conditions that have been associated with excessive inflammation.

Ring-Fused meso-Tetraarylchlorins as Auspicious PDT Sensitizers: Synthesis, Structural Characterization, Photophysics, and Biological Evaluation.

Novel 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-fused meso-tetraarylchlorins, with different degrees of hydrophilicity (with methyl ester, hydroxymethyl, and carboxylic acid moieties), have been synthesized and their photophysical characterization as well as in vitro photocytotoxicity assessment against human melanoma and esophageal and bladder carcinomas was carried out. An integrated analysis of the photosensitizers’ performance, considering the singlet oxygen generation data, cell internalization, and intracellular localization, allowed to establish relevant structure-photoactivity relationships and the rationalization of the observed photocytotoxicity. In the diacid and monoalcohol series, chlorins derived from meso-tetraphenylporphyrin proved to be the most efficient photodynamic therapy agents, showing IC50 values of 68 and 344 nM against A375 cells, respectively. These compounds were less active against OE19 and HT1376 cells, the diacid chlorin with IC50 values still in the nano-molar range, whereas the monohydroxymethyl-chlorin showed significantly higher IC50 values. The lead di(hydroxymethyl)-substituted meso-tetraphenylchlorin confirmed its remarkable photoactivity with IC50 values below 75 nM against the studied cancer cell lines. Subcellular accumulation of this chlorin in the mitochondria, endoplasmic reticulum, and plasma membrane was demonstrated.

Hypoxia-Responsive Azobenzene-Linked Hyaluronate Dot Particles for Photodynamic Tumor Therapy

In this study, we developed ultra-small hyaluronate dot particles that selectively release phototoxic drugs into a hypoxic tumor microenvironment. Here, the water-soluble hyaluronate dot (dHA) was covalently conjugated with 4,4′-azodianiline (Azo, as a hypoxia-sensitive linker) and Ce6 (as a photodynamic antitumor agent), producing dHA particles with cleavable Azo bond and Ce6 (dHA-Azo-Ce6). Importantly, the inactive Ce6 (self-quenched state) in the dHA-Azo-Ce6 particles was switched to the active Ce6 (dequenched state) via the Azo linker (–N=N–) cleavage in a hypoxic environment. In vitro studies using hypoxia-induced HeLa cells (treated with CoCl2) revealed that the dHA-Azo-Ce6 particle enhanced photodynamic antitumor inhibition, suggesting its potential as an antitumor drug candidate in response to tumor hypoxia.

Spectroscopic and photothermal characterization of graphene quantum dots for antimicrobial applications

Antimicrobial resistance is a challenging health problem that demands alternative treatments. Nanoplatforms with antimicrobial properties, associated with photodynamic and photothermal therapies, are potential candidates for this task due to characteristics such as non-invasive, antibiotic-free, dual selectivity, and low adverse effects in therapeutic procedures. Graphene quantum dots are a possible substitute for other nanoparticles, especially by presenting low toxicity and low cost. However, graphene quantum dot properties are highly dependent on the synthesis methods, which makes it difficult to compare and improve methods using different studies. In this work, we apply spectroscopic and photothermal methods to investigate a commercially available green fluorescent graphene quantum dot (GQD) as a potential antimicrobial agent and to determine its theranostics properties. The results showed that the photoactivation of the GQD in phosphate-buffered saline solution by light sources with wavelengths shorter than the emission band can generate singlet oxygen and a heat yield of 50% under excitation at 532 nm, showing the potential of this GQD as a photodynamic and photothermal agent.

Water-soluble chlorin e6-hydroxypropyl chitosan as a high-efficiency photoantimicrobial agent against Staphylococcus aureus

The development of new antimicrobial agents is important to combat infections caused by pathogenic bacteria. Herein, Hydroxypropyl chitosan (HPCS), a hydrophilic modified product of chitosan (CS), was employed as a carrier of the photosensitizer chlorin e6 (Ce6) through an amide bond to obtain the products (HPCS-Ce6 conjugates) with a degree of substitution (DS) ranging from 2.95% to 5.25%. The UV–vis absorption spectra and 1H NMR spectra confirmed the successful synthesis of the products. The products have a better and more stable reactive oxygen species (ROS) generation capacity and higher bacterial affinity than Ce6. At a very low dose (1.8 μg/mL), the highest DS product (HPCS-Ce6-3) can effectively kill Staphylococcus aureus (S. aureus) under 660 nm irradiation. In addition, the HPCS-Ce6 conjugates showed high biocompatibility in the CCK-8 test. The HPCS-Ce6 conjugates could be a photodynamic antibacterial agent with good water solubility, high biocompatibility, and antibacterial activity.

Supramolecular organic frameworks improve the safety of clinically used porphyrin photodynamic agents and maintain their antitumor efficacy

Despite that photodynamic therapy (PDT) has been applied for the treatment of cancer and skin diseases for more than two decades, all clinically used photodynamic agents (PDAs) suffer the drawback of skin phototoxicity of PDAs, which requires patients to avoid exposure to natural light for weeks after treatment, but has so far lacked effective suppression methods. Here, we report that three-dimensional diamondoid supramolecular organic frameworks (SOFs), that possess well-defined 2.1-nm porosity, can be used to suppress the skin phototoxicity of Photofrin, HiPorfin and Talaporfin, three porphyrin-based PDAs which clinically receive the most wide applications by injecting SOF after PDT, via an adsorption and retention mechanism. Fluorescence and dynamic light scattering experiments confirm that the SOFs have strong interaction with PDAs, and can adsorb PDAs at a micromolar concentration, whereas dialysis experiments support that the adsorption leads to an important retention effect. In vitro and in vivo experiments reveal that SOFs have high biocompatibility. Studies with healthy and tumor-bearing mouse models demonstrate that, when the PDAs are administrated at a dose comparable with the clinical one, SOF can remarkably suppress sunlight-induced skin phototoxicity, whereas the PDT efficacy of mice treated with SOF post-PDT is maintained. This work provides an efficient strategy for the improvement of the safety of clinically used PDAs.