Photodynamic Therapy Process Research Articles

Time-gated luminescent probes for lysosomal singlet oxygen: Synthesis, characterizations and bioimaging applications

BackgroudSingle oxygen (1O2), the molecular oxygen at its excited state, plays a crucial role in the photodynamic therapy (PDT) of some diseases owing to its strong oxidizing property to destroy malignant cells. Although the fluorescent probe technique has proven its powerful application abilities for detection of 1O2 in biological systems, most of the reported fluorescent probes suffered from the interference of background autofluorescence of biological samples. It is clear that the real-time and in situ, background-free fluorescent detection of 1O2 generated in live cells, especially in some organelles, is of great significance for understanding the action mechanism of PDT drugs. ResultsBy introducing a lysosome-anchoring motif, a morpholine moiety, into a 1O2-specifically-reactive terpyridine polyacid ligand, [4’-(9-anthryl)-2,2’:6′,2″-terpyridine-6,6″-diyl] bis(methylenenitrilo) tetrakis (acetic acid) (ATTA), and chelating with lanthanide ions (Eu3+ or Tb3+), two lanthanide complex-based “turn-on” luminescent probes that can be used for the background-free time-gated luminescent (TGL) detection of lysosomal 1O2, Lyso-ATTA-Eu3+ and Lyso-ATTA-Tb3+, have been developed. The probes exhibit fast luminescence responses (within 2.5 min) towards 1O2 with high selectivity and sensitivity (<0.75 μM) in a wide pH range (4–11). And the excellent lysosome-localization performance of the probes allowed them to be used for the monitoring of endogenous 1O2 in lysosomes, which enabled the variability of lysosomal-1O2 concentrations induced by different photosensitizers to be successfully discriminated. Furthermore, by doping Lyso-ATTA-Eu3+ into the polyethylene glycol (PEG) hydrogel, the smart luminescent sensor film, PEG-Lyso-ATTA-Eu3+, was prepared, and successfully used for the detection of the on-site 1O2 production during the PDT process of psoriatic disease in model mice. SignificantTwo lysosome-targetable background-free TGL probes for 1O2 were firstly reported. The developed smart luminescent sensor film could be a powerful tool for the clinical monitoring of PDT on skin diseases without using sophisticated and expensive instruments.

Optimizing the administrated light dose during 5-ALA-mediated photodynamic therapy: Murine 4T1 breast cancer model.

Photodynamic therapy (PDT) is already used to treat many cancers, including breast cancer, the most common cancer in women worldwide. The destruction basis of this method is on produced singlet oxygen which is extremely reactive and is a major agent of tumor cell killing. The measurement of singlet oxygen produced within PDT is essential in predicting treatment outcomes and their optimization. This study aims to determine the optimal total light dose administered during PDT by calculating the singlet oxygen to facilitate the prediction of the treatment outcome in mice bearing 4T1 cell breast cancer. Monitoring the changes in photosensitizer fluorescence signals during PDT due to photobleaching can be one of the methods of determination of singlet oxygen generation in the PDT process. This study determined the oxygen singlet as a photodynamic dose from the three-dimensional Monte Carlo method and the photobleaching empirical dose constant. The photobleaching dose constant was established non-invasively by monitoring the invivo protoporphyrin IX (PpIX) fluorescence and photobleaching during PDT. The photobleaching dose constant (β) in J/cm2 was calculated using empirical fluorescence data. The invivo photobleaching dose constant of aminolevulinic acid was found to be 11.6 J/cm2 and based on this value, the optimal treatment light dose was estimated at 120 J/cm2 in mice bearing 4T1 breast cancer. It is concluded that information can be obtained regarding optimal treatment parameters by monitoring the invivo PpIX fluorescence and photobleaching during PDT.

Mitochondria-targeting hemicyanine photosensitizer as an inducer for MMP loss and cell apoptosis based on radical enhanced ISC strategy

Hemicyanine dyes are known as widely used fluorophores with good biocompatibility and excellent photophysical property, but poor ability to produce singlet oxygen has limited their application in photodynamic therapy (PDT). Introduction of heavy atoms seems to be a feasible way to enhance the PDT efficiency, but undesired toxicity is inevitable. Herein, a radical enhanced intersystem crossing-based hemicyanine dye Cy-OT is synthesized and successfully applied in PDT process. The singlet oxygen quantum yield of Cy-OT increases by 4.2 times through the introduction of 4-hydroxyl-2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) unit. Cell experiments carried out in MCF-7 cells demonstrates that Cy-OT is localized in mitochondria and can produce single oxygen under the irradiation of 660 nm light which subsequently results in mitochondria membrane potential (MMP) loss and induces cell apoptosis. The therapeutic experiment of 4T1 tumor bearing mice further indicates that Cy-OT can serve as an ideal photosensitizer with good antitumor effect and negligible side effect to normal tissues.

Metal-Organic Framework-Supported Catalase Delivery for Enhanced Photodynamic Therapy via Hypoxia Mitigation.

Tumor hypoxia poses a significant challenge in photodynamic therapy (PDT), which uses molecular oxygen to produce reactive oxygen species upon light excitation of a photosensitizer. For hypoxia mitigation, an enzyme catalase (CAT) can be beneficially used to convert intracellular hydrogen peroxide to molecular oxygen, but its utility is significantly limited due to the intrinsic membrane impermeability. Herein, we present direct integration of CAT into the outer surface of unmodified metal-organic framework (MOF) nanoparticles (NPs) via supramolecular interactions for effective cellular entry of CAT and consequent enhancement of PDT. The results demonstrated that CAT-loaded MOF NPs could successfully enter hypoxic cancer cells, after which the intracellularly delivered CAT molecules became dissociated from the MOF surface to efficiently initiate the oxygen generation and PDT process along with a co-delivered photosensitizer IR780. This achievement suggests that our protein-MOF integration strategy holds great potential in biomedical studies to overcome tumor hypoxia as well as to efficiently deliver biomolecular cargos.

Three positive charge nonapoptotic-induced photosensitizer with excellent water solubility for tumor therapy

Photodynamic therapy (PDT) has emerged as a significant cancer therapy option. Currently, cation-based organic small molecule aggregation-induced emission (AIE) photosensitizers (PSs) attract the wide attention of many scientists, due to improved reactive oxygen species (ROS) production after cationization. However, such PSs tend to localize only the mitochondria, limiting the death way of tumor cells (usually apoptosis) during PDT process, which may affect the therapeutic effect under some circumstances. Herein, we designed a novel water-soluble three positive charge PS, TPAN-18F, which could be distributed uniformly in cell cytoplasm and had distribution in different sub-organelles (mitochondria, endoplasmic reticulum, lysosome). The experimental results showed that TPAN-18F-based PDT process can not only disrupt mitochondrial functions (reducing ATP production and destroying mitochondrial membrane potential), but also elevate the intracellular lipid peroxides (LPOs) level, which evoke the non-apoptotic death manner of tumor cells. Further, in vivo studies showed that TPAN-18F-based PDT could effectively inhibit tumor growth. Accordingly, we believe that the construction of TPAN-18F is suggestive for tumor non-apoptotic therapy.

Cherenkov Radiation induced photodynamic therapy - repurposing older photosensitizers, and radionuclides

Context: Old-generation photosensitizers are minimally used in current photodynamic therapy (PDT) because they absorb in the UV/blue/green region of the spectrum where biological tissues are generally highly absorbing. The UV/blue light of Cherenkov Radiation (CR) from nuclear disintegration of beta-emitter radionuclides shows promise as an internal light source to activate these photosensitizers within tissue. Outline of the study: 1) radionuclide choice and Cherenkov Radiation, 2) Photosensitizer choice, synthesis and radiolabeling, 3) CR-induced fluorescence, 4) Verification of ROS formation, 5) CR-induced PDT with either free eosine and free CR emitter, or with radiolabelled eosin. Results: Cherenkov Radiation Energy Transfer (CRET) from therapeutic radionuclides (90Y) and PET imaging radionuclides (18F, 68Ga) to eosin was shown by spectrofluorimetry and in vitro, and was shown to result in a PDT process. The feasibility of CR-induced PDT (CR-PDT) was demonstrated in vitro on B16F10 murine melanoma cells mixing free eosin (λabs = 524 nm, ΦΔ 0.67) with free CR-emitter [18F]-FDG under their respective intrinsic toxicity levels (0.5 mM/8 MBq) and by trapping singlet oxygen with diphenylisobenzofuran (DPBF). An eosin-DOTAGA-chelate conjugate 1 was synthesized and radiometallated with CR-emitter [68Ga] allowed to reach 25 % cell toxicity at 0.125 mM/2 MBq, i.e. below the toxicity threshold of each component measured on controls. Incubation time was carefully examined, especially for CR emitters, in light of its toxicity, and its CR-emitting yield expected to be 3 times as much for 68Ga than 18F (considering their β particle energy) per radionuclide decay, while its half-life is about twice as small. Perspective: This study showed that in complete darkness, as it is at depth in tissues, PDT could proceed relying on CR emission from radionuclides only. Interestingly, this study also repurposed PET imaging radionuclides, such as 68Ga, to trigger a therapeutic event (PDT), albeit in a modest extent. Moreover, although it remains modest, such a PDT approach may be used to achieve additional tumoricidal effect to RIT treatment, where radionuclides, such as 90Y, are strong CR emitters, i.e. very potent light source for photosensitizer activation.

Fully Implantable and Retrievable Upconversion Waveguides for Photodynamic Therapy in Deep Tissue

AbstractThe clinical administration of biophotonic approaches, such as photodynamic therapy (PDT), is impeded by the low penetration of visible light in biological tissues. The cooperation of infrared (IR) light with deeper penetration and implantable IR‐to‐visible upconversion materials and devices establishes an effective strategy to generate visible light in deep tissue. In this work, a wirelessly powered upconversion waveguide‐based light source is reported for PDT‐based in vivo cancer treatments in deep tissue. Combining microscale IR‐to‐visible upconversion device arrays and a biocompatible waveguide, the implant exhibits enhanced IR transmission in biological environments and generates upconverted red emission in the target region at a depth &gt;10 mm. The red illumination activates a photosensitizer in 5‐aminolevulinic acid (5‐ALA)‐based PDT treatment, inducing massive apoptosis (&gt;60% cell death) of tumor cells. After implanted in tumor‐bearing mice, the waveguides enable chronic operation for more than two weeks and reveal ideal anti‐tumor efficacies in the PDT process. Finally, the biocompatible waveguide can be retrieved from the tissue, leaving minimal traces after treatments. Such a waveguide implant represents a prospective technique to realize optical‐based biological modulations and medical treatments within the body.

Rational Design of Self-Reporting Photosensitizers for Cell Membrane-Targeted Photodynamic Therapy.

Organelle-targeted photosensitizers (PSs) have demonstrated enhanced phototherapeutic effect by specifically destroying subcellular organelle. As a critical cellular organelle, the cell membrane plays crucial roles in maintaining cell integrity and regulating cellular communications. To date, a variety of membrane-targeted PSs have been developed and shown exceptional therapeutic effects. However, functional PSs that can achieve membrane-targeted photodynamic therapy (PDT) and real-time monitor the therapeutic process have rarely been reported. In particular, the development of self-reporting PS with near-infrared (NIR) absorption is highly desirable but remains a challenge. Herein, we presented two molecular rotor-based self-reporting PSs. One of the PSs, MRMP-2, possesses NIR absorption property, making it a promising candidate for clinical applications. These PSs could not only enable membrane-targeted PDT but also demonstrate selective fluorescence response toward viscosity. In this regard, the fluorescence variation of these PSs could be utilized to indicate the disruption of membrane structure during PDT process. By leveraging the feedback of the fluorescence signal, we could make intuitive judgement about the phototherapeutic results. As a result, these two PSs possess significant potential in the field of imaging-guided PDT.

Photodynamic Therapy: Killing cancer gently with visible light

Photodynamic Therapy: Killing cancer gently with visible light Drs. Mary Potasek, Evgueni Parilov, and Karl Beeson, who are all co-founders of Simphotek, Inc have been using a novel therapeutic modality known as Photodynamic Therapy (PDT) to treat cancer, with far fewer side effects than traditional radiation x-ray methods. By using near-infrared or “gentle” visible light, this PDT does not cause nausea as chemotherapy does, does not damage ordinary tissue as x-ray radiation does, nor does it require removing or damaging parts of the body as surgery does. Simphotek has been supported by the United States National Institute of Health (NIH) to create such a simulation research tool for solid cancers and it’s called Dosie™. Dosie is the first comprehensive tool to simulate the PDT process including the light transport, drug, and molecular oxygen interactions to create the cytotoxic agent, singlet oxygen, which kills cancer. The goal is to treat a tumor’s greatest volume with the least exposure to the major blood vessels or other sensitive areas, which the researchers hope that this clinical trial will bring them one step closer to their aim of treating patients as safely and effectively as possible.

ALA/Ag2S/MnO2 Hybrid Nanoparticles for Near-Infrared Image-Guided Long-Wavelength Phototherapy of Breast Cancer.

The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) based on temperature increase and the formation of reactive oxygen species (ROS), respectively, is an exciting avenue to provide local and improved therapy of tumors with minimal off-site toxicity. 5-Aminolevulinic acid (ALA) is one of the most popular PDT pro-drugs, and its efficiency improves significantly when delivered to tumors with nanoparticles (NPs). But the tumor site's hypoxic environment is a handicap for the oxygen-consuming PDT process. In this work, highly stable, small, theranostic NPs composed of Ag2S quantum dots and MnO2, electrostatically loaded with ALA, were developed for enhanced PDT/PTT combination of tumors. MnO2 catalyzes endogenous H2O2 to O2 conversion and glutathione depletion, enhancing ROS generation and ALA-PDT efficiency. Ag2S quantum dots (AS QDs) conjugated with bovine serum albumin (BSA) support MnO2 formation and stabilization around Ag2S. AS-BSA-MnO2 provided a strong intracellular near-infrared (NIR) signal and increased the solution temperature by 15 °C upon laser irradiation at 808 nm (215 mW, 10 mg/mL), proving the hybrid NP as an optically trackable, long-wavelength PTT agent. In the in vitro studies, no significant cytotoxicity was observed in the absence of laser irradiation in healthy (C2C12) or breast cancer cell lines (SKBR3 and MDA-MB-231). The most effective phototoxicity was observed when AS-BSA-MnO2-ALA-treated cells were co-irradiated for 5 min with 640 nm (300 mW) and 808 nm (700 mW) due to enhanced ALA-PDT combined with PTT. The viability of cancer cells decreased to approximately 5-10% at 50 μg/mL [Ag], corresponding to 1.6 mM [ALA], whereas at the same concentration, individual PTT and PDT treatments decreased the viability to 55-35%, respectively. The late apoptotic death of the treated cells was mostly correlated with high ROS levels and lactate dehydrogenase. Overall, these hybrid NPs overcome tumor hypoxia, deliver ALA to tumor cells, and provide both NIR tracking and enhanced PDT + PTT combination therapy upon short, low-dose co-irradiation at long wavelengths. These agents that may be utilized for treating other cancer types are also highly suitable for in vivo investigations.

Red-to-near-infrared self-reporting photosensitizers with high photostability for photodynamic therapy

Photodynamic therapy (PDT) is a promising tumor treatment method, in which the design of photosensitizers is particularly critical. Red-to-near-infrared (NIR) photosensitizers are beneficial to the implementation of the PDT process. However, the visualizable self-reporting PDT process cannot be fulfilled because most red-to-NIR photosensitizers have poor photostability. Here, we report a photostable red-to-NIR D-A-D photosensitizer (TPA-BPY) using BOPHY as the acceptor and triphenylamine as the donor. As far as we know, TPA-BPY is the first red-to-NIR BOPHY photosensitizer with advantages such as large molar extinction coefficient and high photostability. TPA-BPY can induce the production of singlet oxygen (1O2) under light, successfully achieving photodynamic therapy for MCF-7 cells. More importantly, TPA-BPY achieved self-reporting of the PDT-induced apoptosis process. TPA-BPY was localized in lysosomes and monitored for increased polarity during lysosomal storage and decreased polarity of apoptotic cells. This work provides an effective strategy for constructing polar sensitive near infrared self-reporting photosensitizers for PDT and its process monitoring.

Photosensitized Generation of Singlet Oxygen (1O2) from Pyropheophorbide a Specifically Bound to All Parallel-Stranded G-Quadruplex DNAs.

Pyropheophorbide a (Pyro-a), a chlorophyll metabolite, is a potential photosensitizer for photodynamic therapy (PDT), but little is known about its interaction with the target molecules for PDT, e.g., nucleic acids. Elucidation of the interaction between photosensitizers and nucleic acids will help us understand the initial process of PDT at the molecular level and hence to develop photosensitizing agents. We found that pyro-a forms a 1:1 complex with an all parallel-stranded G-quadruplex DNA and that pyro-a in the complex exhibits a quantum yield for singlet oxygen generation, with excitation at 664 nm, higher by a factor of ∼10 than that of pyro-a in an aqueous solution. These findings provided novel insights into molecular design of pyro-a-based photosensitizers to enhance their PDT efficacy.

Visualization of Phototherapy Evolution by Optical Imaging.

Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is a non-invasive and effective approach used for cancer treatment, in which phototherapeutic agents are irradiated with an appropriate light source to produce cytotoxic reactive oxygen species (ROS) or heat to ablate cancer cells. Unfortunately, traditional phototherapy lacks a facile imaging method to monitor the therapeutic process and efficiency in real time, usually leading to severe side effects due to high levels of ROS and hyperthermia. To realize precise cancer treatment methods, it is highly desired to develop phototherapeutic agents possessing an imaging ability to evaluate the therapeutic process and efficacy in real time during cancer phototherapy. Recently, a series of self-reporting phototherapeutic agents were reported to monitor PDT and PTT processes by combining optical imaging technologies with phototherapy. Due to the real-time feedback provided by optical imaging technology, therapeutic responses or dynamic changes in the tumor microenvironment could be evaluated in a timely manner, thereby achieving personalized precision treatment and minimizing toxic side effects. In this review, we focus on the advances in the development of self-reporting phototherapeutic agents for a cancer phototherapy evaluation based on optical imaging technology to realize precision cancer treatments. Additionally, we propose the current challenges and future directions of self-reporting agents for precision medicine.

Cancer-Cell-Biomimetic Carbazole-Based AIE Nanoplatform for Targeted Phototheranostics of Lung Cancer

Lung cancer is one of the most diagnosed cancers and is the leading cause of cancer death. Photodynamic therapy (PDT) has been considered as a promising strategy due to its strong efficacy and negligible side effects. The development of potent PDT agents with an excellent tumor targeting capability is highly desirable but still not satisfied. In this work, we report a highly efficacious organic nanoplatform based on an aggregation-induced emission luminogen (AIEgen) and biomimetic modification for precise phototheranostics of lung cancer. An AIEgen with strong light absorption ability and bright deep red/near-infrared emission is designed and synthesized that possesses both type I and type II PDT processes. The AIEgen is encapsulated into nanoparticles (NPs) and further camouflaged with a Lewis lung carcinoma cell membrane to build a biomimetic nanoplatform. Both in vitro and in vivo experiments indicate that the cancer-cell-biomimetic NPs could significantly increase the tumor cell targeting ability and sensitively delineate the tumor site. Moreover, the cell-membrane-camouflaged NPs also show excellent antitumor efficacy in lung-cancer-bearing mice. This work demonstrates that the integration of highly efficient AIEgen and biomimetic cell membranes is able to boost the phototheranostic efficacy, representing a promising strategy for precise cancer diagnosis and treatment.

Simulation of Time and Frequency Domain of Photosensitizers Effect During Light Transport through Tissue as Applied to Photodynamic Therapy using a Steady State Monte Carlo Method with Simulink

Photodynamic therapy (PDT) is a treatment process that makes use of a non-ionizing light source targeted at specific section of cells (a tumor) in order to induce apoptosis, and eventually, the death of cells in such area. This is achieved using specific light sensitive photosensitizing (PS) agents (in the case of this research Metvix-Methyl Aminolevulinate (MAL)) used to saturate the treatment area for a recorded time period before irradiating with non-ionizing light source. This research was designed to observe the time and frequency domains as the PS signal decays during the PDT process. During the process, the PS agent degenerates and becomes less and less interactive with the light source. Using the Hop/drop/spin nomenclature, the source of the incident photon is simulated using A Gaussian White Noise (AGWN) on Simulink and the incident signal is allowed to attenuate through the target area while the time and frequency domain of the photosensitizer MAL is recorded as it decays. It is observed that the amplitude of the absorption coefficient of the PS agent dropped to almost 0 during a short sample time while the normalized frequency decays with a highly damped and irregular oscillatory pattern. The improvement in attenuation due to the presence of the PS agent degenerates sharply during the initial state of the treatment in order to ensure that the generation of singlet oxygen terminates just after treatment time.

A self-reporting photosensitizer for inducing and in-situ monitoring lysosomal damage and cell apoptosis

Photodynamic therapy (PDT) is a desirable method to fight against cancer, because it can achieve selective ablation of tumor tissues via the control of incident light. Self-reporting PDT sensitizers that can in-situ and real-timely monitor cell viability during PDT process are promising tools for PDT. For lysosomal damage would release cathepsins B/D into cytoplasm and efficiently induce cell apoptosis, herein, we have constructed a unique self-reporting PDT sensitizer (NSLN) targeting lysosomes in living cells. NSLN was designed to equip both alkalescent unit and cationic group. And NSLN targeted lysosomes in living cells, and immigrated into nucleus after lysosomal damage and cell death. In this way, the cells viability could be facilely visualized via subcellular localization of NSLN. With the probe, the apoptosis induced by H2O2, rotenone, and paclitaxel has been successfully monitored. Furthermore, NSLN could generate large amount of reactive oxygen species and induce lysosomal damage and cell apoptosis upon light irradiation. The cell damage during PDT procedure could be also monitored with NSLNvia its subcellular immigration. This work provides a novel method for monitoring PDT process and makes it possible to control phototoxicity. We believe that NSLN can be used as a powerful tool to promote the development of PDT.

Oxygen supplementation liposomes for rheumatoid arthritis treatment via synergistic phototherapy and repolarization of M1-to-M2 macrophages

Rheumatoid arthritis (RA) is one of the most common systemic autoimmune diseases, with no current, clinically effective treatment. Activation of pro-inflammatory M1 macrophages is known to play a vital role in the pathogenesis of RA. Accumulating evidence suggests that phototherapy, especially photodynamic therapy (PDT), could apply as a new therapeutic method for the treatment of RA. However, due to the anoxic environment of RA synovial tissues and the oxygen consumption required for PDT process, the phototherapy efficiency was always reduced. Moreover, surviving and newly invading macrophages will be induced to polarize towards the pro-inflammatory M1-type, resulting in a relapse of the disease. To compensate for these deficits, we designed and developed novel phototherapeutic liposomal nanoparticles (CyI&Hb/FA-LPs) by incorporating heavy atom modified, cyanine dyes (CyI) as photosensitizers, and loading hemoglobin (Hb) into the inner core for relieving the hypoxic microenvironments and repolarizing M1-to-M2 macrophages. Meanwhile, folic acid was attached to the liposome surface to achieve active targeting of M1 macrophages. In vitro and in vivo studies demonstrate that near infrared light irradiation of CyI&Hb/FA-LPs reduces M1 macrophage populations and reduces the expression of hypoxia-inducible factor-1α that drives the remaining M1 macrophages to transition to the anti-inflammatory M2 phenotype. Moreover, intra-articular treatment of CyI&Hb/FA-LPs in a RA mouse model inhibited synovial cell infiltration, and alleviated inflammation and pathological features in the affected joint. This study highlights the potential of CyI-based oxygenated liposomes as a new and versatile strategy for implementing RA targeting phototherapy and M1-to-M2 repolarization. The dual mode phototherapy and O2 supplementation agent appears to function synergistically by reducing M1 macrophage populations through direct killing and induced apoptosis, as well as by inducing M2 phenotype proliferation.

Plasmon-enhanced nano-photosensitizers: game-changers in photodynamic therapy of cancers.

Plasmonic nanostructures can be used to tackle the shortcomings of conventional photosensitizers in photodynamic therapy (PDT) of cancers, including their low reactive oxygen species (ROS) quantum yield, stability, and targetability. However, the positive role of plasmonic nanostructures is not limited to their ability for ROS generation or singlet oxygen formation. The main advantage of plasmonic nanostructures relies on the collective oscillation of free electrons, the so-called surface plasmon resonance (SPR), which can trigger plenty of optical phenomena in their near-field. Surface plasmon resonance is highly dependent on the morphology, size, and composition of the plasmonic nanostructure, which can give one the ability to control the wavelength of light-matter interaction, which is highly desirable in PDT applications. This review has focused on the conjugation of plasmonic nanostructures with organic compounds, biological compounds, ceramic nanoparticles, polymeric nanoparticles, metal-organic frameworks (MOFs), and magnetic nanoparticles from a mechanistic point of view. Hybridization of plasmonic nanoparticles would enable plenty of optical mechanisms beneficial for the PDT process that has been extensively discussed by presenting the most recent efforts in each category. This review can be a useful guideline for researchers working on enhancing the efficiency of the PDT process and those interested in plasmon-enhanced phenomena by emphasizing the underlying mechanisms.

Graphene Quantum Dots Modified Upconversion Nanoparticles for Photodynamic Therapy.

Photodynamic therapy (PDT), as a novel technique, has been extensively employed in cancer treatment by utilizing reactive oxygen species (ROS) to kill malignant cells. However, most photosensitizers (PSs) are short of ROS yield and affect the therapeutic effect of PDT. Thus, there is a substantial demand for the development of novel PSs for PDT to advance its clinical translation. In this study, we put forward a new strategy for PS synthesis via modifying graphene quantum dots (GQDs) on the surface of rare-earth elements doped upconversion nanoparticles (UCNPs) to produce UCNPs@GQDs with core-shell structure. This new type of PSs combined the merits of UCNPs and GQDs and produced ROS efficiently under near-infrared light excitation to trigger the PDT process. UCNPs@GQDs exhibited high biocompatibility and obvious concentration-dependent PDT efficiency, shedding light on nanomaterials-based PDT development.

NIR-II Ratiometric Chemiluminescent/Fluorescent Reporters for Real-Time Monitoring and Evaluating Cancer Photodynamic Therapy Efficacy.

The development of probes for early monitoring tumor therapy response may greatly benefit the promotion of photodynamic therapy (PDT) efficacy. Singlet oxygen (1 O2 ) generation is a typical indicator for evaluating PDT efficacy in cancer. However, most existing probes cannot quantitatively detect 1 O2 in vivo due to the high reactivity and transient state, and thus have a poor correlation with PDT response. Herein, a 1 O2 -responsive theranostic platform comprising thiophene-based small molecule (2SeFT-PEG) and photosensitizer Chlorin e6 (Ce6) micelles for real-time monitoring PDT efficacy is developed. After laser irradiation, the Ce6-produced 1 O2 could simultaneously kill cancer and trigger 2SeFT-PEG to produce increased chemiluminescence (CL) and decreased fluorescence (FL) signals variation at 1050nm in the second near-infrared (NIR-II, 950-1700nm) window. Significantly, the ratiometric NIR-II CL/FL imaging at 1050nm could effectively quantify and monitor the concentration of 1 O2 and O2 consumption or recovery, so as to evaluate the therapeutic efficacy of PDT in vivo. Hence, this 1 O2 activated NIR-II CL/FL probe provides an efficient ratiometric optical imaging platform for real-time evaluating PDT effect and precisely guiding the PDT process in vivo.