Near-infrared Photosensitizer Research Articles

Aza-BODIPY based carbonic anhydrase IX: Strategy to overcome hypoxia limitation in photodynamic therapy.

Hypoxia caused by photodynamic therapy (PDT) is a major hurdle to cancer treatment since it can promote recurrence and progression by activating angiogenic factors, lowering therapeutic efficacy dramatically. In this work, AZB-I-CAIX2 was developed as a carbonic anhydrase IX (CAIX)-targeting NIR photosensitizer that can overcome the challenge by utilizing a combination of CAIX knockdown and PDT. AZB-I-CAIX2 showed a specific affinity to CAIX-expressed cancer cells and enhanced photocytotoxicity compared to AZB-I-control (the molecule without acetazolamide). Moreover, selective detection and effective cell cytotoxicity of AZB-I-CAIX2 by PDT in hypoxic CAIX-expressed murine cancer cells were achieved. Essentially, AZB-I-CAIX2 could minimize tumor size in the tumor-bearing mice compared to that in the control groups. The results suggested that AZB-I-CAIX2 can improve therapeutic efficiency by preventing PDT-induced hypoxia through CAIX inhibition.

Photodynamic properties of lysine and arginine derivatives of bacteriopurpurinimide.

Background: O-propyloxime-N-propoxybacteriopurpurinimide methyl ester (3) is a near-infrared photosensitizer with confirmed in vivo anticancer activity. Methods: Conjugates of 3 with arginine (1) or lysine attached at an ε-amino group (2a) or α-amino group (2b) were studied as anticancer and antibacterial photosensitizers and compared with 3. Results: The new conjugates preserve advanced spectral characteristics of 3 and high singlet oxygen quantum yield. They demonstrated tenfold higher photocytotoxicity for cancer cells, due to their enhanced intracellular accumulation and altered localization. Though they showed threefold decreased antibacterial photodynamic effect compared with 3, they kill planktonic Staphylococcus aureus bacteria, and 1 destroys bacterial biofilms. Conclusion: Conjugates 1 and 2b are near-infrared photosensitizers with high anticancer and limited antibacterial activity.

A Carbon Nanodot Based Near-Infrared Photosensitizer with a Protein-Ruthenium Shell for Low-Power Photodynamic Applications.

Near-infrared (NIR) light-activated photosensitization represents an encouraging therapeutic method in photodynamic therapy, especially for deep tissue penetration. In this context, two-photon activation, i.e., utilization of photons with relatively low energy but high photon flux for populating a virtual intermediate state leading to an excited state, is attractive. This concept would be highly advantageous in photodynamic therapy due to its minimal side effects. Herein, we propose that the combination of plasma protein serum albumin (HSA) containing several Ru complexes and NIR two-photon excitable carbon nanodots (Cdots), termed HSA-Ru-Cdots, provides several attractive features for enhancing singlet oxygen formation within the mitochondria of cancer cells stimulated by two-photon excitation in the NIR region. HSA-Ru-Cdot features biocompatibility, water solubility, and photostability as well as uptake into cancer cells with an endosomal release, which is an essential feature for subcellular targeting of mitochondria. The NIR two-photon excitation induced visible emission of the Cdots allows fluorescence resonance energy transfer (FRET) to excite the metal-to-ligand charge transfer of the Ru moiety, and fluorescence-lifetime imaging microscopy (FLIM) has been applied to demonstrate FRET within the cells. The NIR two-photon excitation is indirectly transferred to the Ru complexes, which leads to the production of singlet oxygen within the mitochondria of cancer cells. Consequently, we observe the destruction of filamentous mitochondrial structures into spheroid aggregates within various cancer cell lines. Cell death is induced by the long-wavelength NIR light irradiation at 810 nm with a low power density (7 mW/cm2), which could be attractive for phototherapy applications where deeper tissue penetration is crucial.

Chemiluminescence in Combination with Organic Photosensitizers: Beyond the Light Penetration Depth Limit of Photodynamic Therapy.

Photodynamic therapy (PDT) is a promising noninvasive medical technology that has been approved for the treatment of a variety of diseases, including bacterial and fungal infections, skin diseases, and several types of cancer. In recent decades, many photosensitizers have been developed and applied in PDT. However, PDT is still limited by light penetration depth, although many near-infrared photosensitizers have emerged. The chemiluminescence-mediated PDT (CL-PDT) system has recently received attention because it does not require an external light source to achieve targeted PDT. This review focuses on the rational design of organic CL-PDT systems. Specifically, PDT types, light wavelength, the chemiluminescence concept and principle, and the design of CL-PDT systems are introduced. Furthermore, chemiluminescent fraction examples, strategies for combining chemiluminescence with PDT, and current cellular and animal applications are highlighted. Finally, the current challenges and possible solutions to CL-PDT systems are discussed.

A Selenium-Substituted Heptamethine Cyanine Photosensitizer for Near-Infrared Photodynamic Therapy.

Photodynamic therapy (PDT) is a relatively safe approach to cancer treatment without significant systemic side effects or drug resistance. However, the current PDT efficiency is unsatisfactory due to the lack of near-infrared (NIR) photosensitizers. Heptamethine cyanine (Cy7) dyes are well-known NIR fluorophores and are also used as photosensitizers. But their singlet oxygen quantum yields (ΦΔ ) are not ideal. Herein, we developed an NIR photosensitizer with a long-lived excited triplet state (τ=4.3 μs) by introducing a selenium atom into the structure of a Cy7 dye. The new NIR photosensitizer exhibits a significantly high singlet oxygen quantum yield (ΦΔ =0.11). Its good PDT effect was demonstrated in the living cells. Considering that the selenium-substituted photosensitizer has a very low dark cytotoxicity and good chemical stability, we conclude that it will have a promising future in biomedical and clinical applications.

Rational Modulation of BODIPY Photosensitizers to Design Metal-Organic Framework-Based NIR Nanocomposites for High-Efficiency Photodynamic Therapy in a Hypoxic Environment.

Photodynamic therapy (PDT) is a promising noninvasive treatment that has drawn great attention. However, the hypoxic environment in tumors seriously limits the therapeutic effect of oxygen-dependent chemicals and PDT. Herein, a versatile nanocomposite DF-BODIPY@ZIF-8 with oxygen-generating ability was developed based on zeolitic imidazolate framework-8 (ZIF-8) by loading the near-infrared photosensitizer DF-BODIPY to overcome hypoxia-induced drug resistance in cancer therapy. ZIF-8 can catalyze the decomposition of hydrogen peroxide in tumors and increase the dissolved oxygen concentration, resulting in a significant improvement in PDT efficacy. Additionally, we found that enhancing the electronegativity of substituents can effectively reduce the energy level difference (ΔEst) between the minimum singlet state (S1) and the lowest triplet state (T1), leading to the enhancement of the singlet oxygen quantum yield. In vitro experiments suggested that DF-BODIPY@ZIF-8 indeed had a higher singlet oxygen quantum yield and better tumor cell phototoxicity than free DF-BODIPY. In vivo experiments also demonstrated that DF-BODIPY@ZIF-8 could effectively eliminate 4T1 tumors under light irradiation. Thus, we conclude that increasing the electronegativity of substituents and introducing a ZIF-8 material can effectively improve the singlet oxygen quantum yield and overcome the hypoxia limitations for high-efficiency PDT.

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.

Fluorescence imaging-guided photothermal therapy of asymmetric water-soluble pentamethine cyanine for colorectal cancer

The combination of advanced optical technology and tumor treatment has developed into a selectively targeted tumor therapy strategy. Near-infrared (NIR) cyanine derivative has recently received increasing attention in photothermal therapy (PTT) because of its excellent biocompatibility, non-immunogenicity, high fluorescence and photothermal conversion efficiency, photostability, and tumor-homing. In this study, an asymmetric and water-soluble pentamethine cyanine was designed and synthesized to investigate the photosensitive activity and to explore its potential applications as a NIR photosensitizer for the diagnosis and therapy of colorectal cancer (CRC). The results of fluorescence imaging analysis showed that CY5-664 preferentially accumulated in the tumor as time elapsed, and the maximum fluorescence intensity was obtained at 24 h. Cell viability and animal xenograft model experiments showed that CY5-664 significantly inhibited tumor growth in vivo with 0.8 W/cm2 of 660 nm red laser pointer for 2 min, and in vitro with 0.5 W/cm2 of 660 nm red laser pointer for 2 min. In vitro and in vivo photothermal conversion experiments showed that CY5-664 exhibited an anti-CRC activity mainly through the PTT effect. Therefore, this work provides experimental evidence that CY5-664 is a drug candidate for CRC treatment mainly through the PTT effect and an alternative treatment strategy to develop a pentamethine cyanine-based CRC theranostic photosensitizer for synergistic CRC targeting, imaging, and therapy.

On the mechanisms of photodynamic action of photosensitizers based on polycationic derivatives of synthetic bacteriochlorin against human lung cancer cells A549 (in vitro study)

BackgroundOne of the tasks of anticancer photodynamic therapy is increasing the efficacy of treatment of cancer nodes with large (clinically relevant) sizes using near-infrared photosensitizers (PS). We study the photodynamic action against A549 human lung cancer cells using PS based on polycationic derivatives of synthetic bacteriochlorin. MethodsThe efficacy and mechanisms of the photodynamic action of PS based on polycationic derivatives of synthetic bacteriochlorin against A549 lung cancer cells were studied in vitro using immunocytochemical and morphological methods. ResultsIt was found that PS based on tetracationic and octacationic derivatives of synthetic bacteriochlorin induce necrosis, apoptosis, decreasing of proliferative and mitotic activity, as well as reducing the number of ALDH1-positive cancer cells with signs of stem cells in A549 human lung cancer cell culture. The IC50 values (concentration of a PS that reduces cells survival by 50%) were about 0.69 μM for tetracationic PS and 0.57 μM for octacationic PS under irradiation at 30 J/cm2 while in the “dark” control they were higher than 100 μM for both PSs. ConclusionsPhotosensitizers based on polycationic derivatives of synthetic bacteriochlorin have high phototoxicity against A549 cancer cells caused by the induction of necrosis and apoptosis of cancer cells, including cells with signs of stemness, and a sharp decrease of mitotic and proliferative activity.

Rational design and synthesis of novel NIR photosensitizers and application in antimicrobial photodynamic inactivation

Herein we use our previously developed strategy for the synthesis of NIR photosensitizers based on Malachite Green (MG) skeleton. Firstly, we installed bipyridine group into MG to form bpy-MG, as bidentate chelating ligand, which was then bonded with [Ir(ppy)2Cl]2 (ppy = 2-phenylpyridine) and [Ir(dqpx)2Cl]2 (dqpx = 2,3-diphenylquinoxaline) through the N atoms of bipyridine to produce Ir-MG-ppy and Ir-MG-dqpx, respectively. The photosensitizers display NIR absorption with weak fluorescence and singlet oxygen generation ability because of the free rotation of the indoline moieties. Upon binding with deoxyribonucleic acid sodium salt from salmon testes, the fluorescence and singlet oxygen generation ability were greatly boosted due to the restriction of free rotation. The as-prepared photosensitizers demonstrate potential application in light-induced killing Staphylococcus aureus both in vitro and in vivo.

Photochemical α-Aminonitrile Synthesis Using Zn-Phthalocyanines as Near-Infrared Photocatalysts.

While photochemical transformations with sunlight almost exclusively utilize the UV-vis part of the solar spectrum, the majority of the photons emitted by the sun have frequencies in the near-infrared region. Phthalocyanines show high structural similarity to the naturally occurring light-harvesting porphyrins, chlorins, and mainly bacteriochlorins and are also known for being efficient and affordable near-infrared light absorbers as well as triplet sensitizers for the production of singlet oxygen. Although having been neglected for a long time in synthetic organic chemistry due to their low solubility and high tendency toward aggregation, their unique photophysical properties and chemical robustness make phthalocyanines attractive photocatalysts for the application in near-infrared-light-driven synthesis strategies. Herein, we report a cheap, simple, and efficient photocatalytic protocol, which is easily scalable under continuous-flow conditions. Various phthalocyanines were studied as near-infrared photosensitizers in oxidative cyanations of tertiary amines to generate α-aminonitriles, a synthetically versatile compound class.

Indomethacin-based near-infrared photosensitizer for targeted photodynamic cancer therapy

Near-IR fluorescent sensitizers based on heptamethine cyanine (Cy820 and Cy820–IMC) were synthesized and their abilities to target and abolish tumor cells via photodynamic therapy (PDT) were explored. Some hepthamethine cyanine dyes can be transported into cancer cells via the organic anion transporting polypeptides (OATPs). In this study, we aimed to enhance the target ability of the sensitizer by conjugation Cy820 with indomethacin, a non-steroidal anti-inflammatory drug (NSAID), to obtain Cy820–IMC that aimed to target cyclooxygenase–2 (COX–2) which overexpresses in cancer cells. The results showed that Cy820–IMC internalized the cancer cells faster than Cy820 which was verified to be related to COX–2 level and OATPs. Based on PDT experiments, Cy820–IMC has higher photocytotoxicity index than Cy820, >7.13 and 4.90, respectively, implying that Cy820–IMC showed better PDT property than Cy820. However, Cy820 exhibits slightly higher normal-to-cancer cell toxicity ratio than Cy820–IMC, 6.58 and 3.63, respectively. Overall, Cy820–IMC has superior cancer targetability and enhanced photocytoxicity. These characteristics can be further improved towards clinically approved sensitizers for PDT.

RETRACTED ARTICLE: Artificial photoactive chlorophyll conjugated vanadium carbide nanostructure for synergistic photothermal/photodynamic therapy of cancer

Optically active nanostructures consisting of organic compounds and metallic support have shown great promise in phototherapy due to their increased light absorption capacity and high energy conversion. Herein, we conjugated chlorophyll (Chl) to vanadium carbide (V2C) nanosheets for combined photodynamic/photothermal therapy (PDT/PTT), which reserves the advantages of each modality while minimizing the side effects to achieve an improved therapeutic effect. In this system, the Chl from Leptolyngbya JSC-1 extracts acted as an efficient light-harvest antenna in a wide NIR range and photosensitizers (PSs) for oxygen self-generation hypoxia-relief PDT. The available large surface of two-dimensional (2D) V2C showed high Chl loading efficiency, and the interaction between organic Chl and metallic V2C led to energy conversion efficiency high to 78%. Thus, the Chl/ V2C nanostructure showed advanced performance in vitro cell line killing and completely ablated tumors in vivo with 100% survival rate under a single NIR irradiation. Our results suggest that the artificial optical Chl/V2C nanostructure will benefit photocatalytic tumor eradication clinic application.Graphical

Regulating the bacterial oxygen microenvironment via a perfluorocarbon-conjugated bacteriochlorin for enhanced photodynamic antibacterial efficacy

Photodynamic therapy (PDT) has attracted considerable attention, since it could effectively kill bacteria and prevent the development of multi-drug resistance. However, PDT currently suffers from oxygen limitation and hypoxia is a prominent feature of pathological states encountered in inflammation, wounds, and bacterial infections. Herein, an oxygen-tunable nanoplatform based on perfluorocarbon-conjugated tetrafluorophenyl bacteriochlorin (FBC-F) was designed for effective antimicrobial therapy. The introduction of fluorine atoms can not only increase the reactive oxygen species (ROS) production capacity of FBC-F by facilitating the intersystem crossing (ISC) process of FBC photosensitizers, but also make FBC-F deliver more oxygen into the treatment sites benefiting from the outstanding oxygen-dissolving capability of perfluorocarbon. As a consequence, the FBC-F nanoplatform was able to efficiently generate singlet oxygens for type II PDT, as well as superoxide anions and hydroxyl radicals for type I PDT, and significantly improve antibacterial efficacy in vitro. In vivo experiments further proved that the FBC-F with a powerful antibacterial capability could well promote wound healing and destroy biofilm. Thus, this FBC-F nanoplatform may open a new path in photodynamic antibacterial therapy. Statement of significancePhotodynamic therapy is a promising antibacterial treatment, but its efficacy is severely compromised by hypoxia. To overcome such a limitation, we constructed an oxygen-regulated nanoplatform (FBC-F) by attaching perfluorocarbons (PFC) to the NIR photosensitizer (FBC). As an analogue of bacteriochlorin, FBC could generate 1O2 through energy transfer , as well as O2−· and ·OH through electron transfer for synergistic type I and type II photodynamic antibacterial therapy. Benefiting from the oxygen-dissolving capability of PFC, FBC-F could efficiently deliver more oxygen into the treatment site and alleviate the hypoxic environment. As a consequence, FBC-F could effectively generate large amounts of reactive oxygen species to achieve improved antibacterial efficacy and provide a promising approach for eliminating biofilms.

Engineering Supramolecular Nanomedicine for Targeted Near Infrared-triggered Mitochondrial Dysfunction to Potentiate Cisplatin for Efficient Chemophototherapy.

Combinatorial cancer therapies based on nanomedicine have emerged as a promising strategy to achieve potentiated treatment efficiency. Herein, cisplatin (CDDP) prodrug (Pt-CD) and a mitochondria-targeted near-infrared (NIR) photosensitizer IR780 were combined to construct a multifunctional nanomedicine IR780@Pt NPs through a supramolecular self-assembly strategy. Targeted mitochondrial dysfunction of cancer cells was sufficiently induced under NIR laser irradiation through both photothermal and photodynamic effects, inhibiting the overactive mitochondrial energy pathways of cancer cells. The mitochondrial dysfunction significantly attenuated the crosstalk between mitochondria and nucleus via the cellular ATP energy chain, leading to obvious down-regulation of the key proteins of the nucleotide excision repair (NER) pathway. Thereby, the chemotherapeutic effect of CDDP could be significantly potentiated because of reduced DNA lesion repair capacity by ERCC1-XPF nuclease system. Moreover, IR780@Pt NPs exhibited excellent NIR fluorescence and photoacoustic (PA) imaging capacity for in vivo imaging-guided NIR laser treatment. Ultimately, the IR780@Pt NPs mediated combinatorial chemophototherapy achieved potentiated anticancer efficacy against cancer cells in vitro and tumor inhibition performance in vivo. Overall, this study highlighted the significance of nanomedicine mediated targeted induction of mitochondrial dysfunction to potentiate chemotherapy for efficient combinatorial cancer therapy.

Virus-Inspired Hollow Mesoporous Gadolinium-Bismuth Nanotheranostics for Magnetic Resonance Imaging-Guided Synergistic Photodynamic-Radiotherapy.

The anti-tumor efficacy of single photodynamic therapy (PDT) and radiotherapy (RT) has been greatly affected by inadequate tumor uptake of photo/radiation sensitizers, limited laser penetration depth, and radiation sickness caused by high doses of X-rays. Here, the authors report a biomimetic coronavirus-inspired hollow mesoporous gadolinium/bismuth nanocarrier loaded with a new NIR photosensitizer HB (termed as HB@VHMBi-Gd) for magnetic resonance imaging (MRI)-guided synergistic photodynamic-RT. HB@VHMBi-Gd displayed a faster cellular uptake rate than the conventional spherical HMBi-Gd loaded with HB (HB@SHMBi-Gd) because of rough surface-enhanced adhesion. After intravenous injection, HB@VHMBi-Gd is efficiently delivered to the tumor and rapidly invades the tumor cells by surface spikes. Interestingly, lysosomal acidity can trigger the degradation of VHMBi-Gd to produce ultrasmall nanoparticles to amplify the X-ray attenuation ability and enhance MRI contrast and radiosensitization. Under laser and X-ray irradiation, HB@VHMBi-Gd significantly enhances 1 O2 generation from HB to induce activation of caspase 9/3 and inhibition of C-myc, while enhancing hydroxyl radical generation from Bi2 O3 to induce intense DNA breakage. By synergistically inducing cell apoptosis by distinct reactive oxygen species (ROS), HB@VHMBi-Gd exhibits superior anticancer efficacy with ≈90% tumor inhibition. They envision that biomimetic virus-inspired hollow hybrid metal nanoparticles can provide a promising strategy for imaging-guided synergistic photodynamic-RT.

Changes in Spectral Fluorescence Properties of a Near-Infrared Photosensitizer in a Nanoform as a Coating of an Optical Fiber Neuroport

In this work, we tested a new approach to assess the presence of inflammatory process in the implant area using spectral methods and the technique of fiber fluorescence analysis of photosensitizers in nanoform. First of all, the spectral characteristics of the photosensitizer when interacting with the porous surface of the implant, based on hydroxyapatite under in vitro and in vivo conditions, were determined. Thus, it was shown that spectral characteristics of photosensitizers can be used for judgement on the process of inflammation in the implant area and thus on the local presence of the immunocompetent cells. The analysis was performed at a sufficient depth in the biotissue by using the near-infrared spectral region, as well as two different methods: fiber-based laser spectroscopy and fiber-optic neuroscopy, which served to monitor the process and regular fluorescence diagnosis of the studied area. Fluorescence spectroscopic analysis was performed on experimental animals in vivo, i.e., under conditions of active immune system intervention, as well as on cell cultures in vitro in order to judge the role of the immune system in the interaction with the implant in comparison. Thus, the aim of the study was to determine the relationship between the fluorescence signal of nanophotosensitizers in the near infrared spectral region and its parameters with the level of inflammation and the type of surface with which the photosensitizer interacts in the implant area. Thus, fiber-optic control opens up new approaches for further diagnosis and therapy in the implant area, making immune cells a prime target for advanced therapies.

Thermal-sensitive lipid nanoparticles potentiate anti-PD therapy through enhancing drug penetration and T lymphocytes infiltration in metastatic tumor

The response rate of anti-PD therapy in most cancer patients remains low. Therapeutic drug and tumor-infiltrating lymphocytes (TILs) are usually obstructed by the stromal region within tumor microenvironment (TME) rather than distributed around tumor cells, thus unable to induce the immune response of cytotoxic T cells. Here, we constructed the cationic thermosensitive lipid nanoparticles IR780/DPPC/BMS by introducing cationic NIR photosensitizer IR-780 iodide (IR780) modified lipid components, thermosensitive lipid DPPC and PD-1/PD-L1 inhibitor BMS202 (BMS). Upon laser irradiation, IR780/DPPC/BMS penetrated into deep tumor, and reduced cancer-associated fibroblasts (CAFs) around tumor cells to remodel the spatial distribution of TILs in TME. Interestingly, the cationic IR780/DPPC/BMS could capture released tumor-associated antigens (TAAs), thereby enhancing the antigen-presenting ability of DCs to activate cytotoxic T lymphocytes. Moreover, IR780/DPPC/BMS initiated gel-liquid crystal phase transition under laser irradiation, accelerating the disintegration of lipid bilayer structure and leading to the responsive release of BMS, which would reverse the tumor immunosuppression state by blocking PD-1/PD-L1 pathway for a long term. This combination treatment can synergistically exert the antitumor immune response and inhibit the tumor growth and metastasis.

Fluorescent Phthalocyanine-Encapsulated Bovine Serum Albumin Nanoparticles: Their Deployment as Therapeutic Agents in the NIR Region.

In recent times, researchers have aimed for new strategies to combat cancer by the implementation of nanotechnologies in biomedical applications. This work focuses on developing protein-based nanoparticles loaded with a newly synthesized NIR emitting and absorbing phthalocyanine dye, with photodynamic and photothermal properties. More precisely, we synthesized highly reproducible bovine serum albumin-based nanoparticles (75% particle yield) through a two-step protocol and successfully encapsulated the NIR active photosensitizer agent, achieving a good loading efficiency of 91%. Making use of molecular docking simulations, we confirm that the NIR photosensitizer is well protected within the nanoparticles, docked in site I of the albumin molecule. Encouraging results were obtained for our nanoparticles towards biomedical use, thanks to their negatively charged surface (−13.6 ± 0.5 mV) and hydrodynamic diameter (25.06 ± 0.62 nm), favorable for benefitting from the enhanced permeability and retention effect; moreover, the MTT viability assay upholds the good biocompatibility of our NIR active nanoparticles. Finally, upon irradiation with an NIR 785 nm laser, the dual phototherapeutic effect of our NIR fluorescent nanoparticles was highlighted by their excellent light-to-heat conversion performance (photothermal conversion efficiency 20%) and good photothermal and size stability, supporting their further implementation as fluorescent therapeutic agents in biomedical applications.

An Approach to Developing Cyanines with Simultaneous Intersystem Crossing Enhancement and Excited-State Lifetime Elongation for Photodynamic Antitumor Metastasis.

Heavy-atom-based photosensitizers usually exhibit shortened triplet-state lifetimes, which is not ideal for hypoxic tumor photodynamic therapy. Although several heavy-atom-free photosensitizers possess long triplet-state lifetimes, the clinical applicability is limited by their short excitation wavelengths, poor photon capture abilities, and intrinsically hydrophobic structures. Herein we developed a novel NIR heavy-atom-free photosensitizer design strategy by introducing sterically bulky and electron-rich moieties at the meso position of the pentamethine cyanine (Cy5) skeleton, which simultaneously enhanced intersystem crossing (ISC) and prolonged excited-state lifetime. We found that the 1O2 generation ability is directly correlated to the electron-donating ability of the meso substituent in cyanine, and the excited-state lifetime was simultaneously much elongated when the substituents were anthracene derivatives substituted at the 9-position. Our star compound, ANOMe-Cy5, exhibits intense NIR absorption, the highest 1O2 quantum yield (4.48-fold higher than Cy5), the longest triplet-state lifetime (9.80-fold longer than Cy5), and lossless emission intensity (nearly no change compared with Cy5). Such excellent photophysical properties coupled with its inherently cationic and hydrophilic nature enable the photosensitizer to realize photoablation of solid tumor and antitumor lung metastasis. This study highlights the design of a new generation of NIR photosensitizers for imaging-guided photodynamic cancer treatment.