Neutral Cyanine: Ultra-Stable NIR-II Merocyanines for Highly Efficient Bioimaging and Tumor-Targeted Phototheranostics.

Fluorescence imaging (FLI)-guided phototheranostics using emission from the second near-infrared (NIR-II) window show significant potential for cancer diagnosis and treatment. Clinical imaging-used polymethine ionic indocyanine green (ICG) dye is widely adopted for NIR fluorescence imaging-guided photothermal therapy (PTT) research due to its exceptional photophysical properties. However, ICG has limitations such as poor photostability, low photothermal conversion efficiency (PCE), short-wavelength emission peak, and liver-targeting issues, which restrict its wider use. In this study, two ionic ICG derivatives are transformed into neutral merocyanines (mCy) to achieve much-enhanced performance for NIR-II cancer phototheranostics. Initial designs of two ionic dyes show similar drawbacks as ICG in terms of poor photostability and low photothermal performance. One of the modified neutral molecules, mCy890, shows significantly improved stability, an emission peak over 1000 nm, and a high photothermal PCE of 51%, all considerably outperform ICG. In vivo studies demonstrate that nanoparticles of the mCy890 can effectively accumulate at the tumor sites for cancer photothermal therapy guided by NIR-II fluorescence imaging. This research provides valuable insights into the development of neutral merocyanines for enhanced cancer phototheranostics.

A Stable Open-Shell Conjugated Diradical Polymer with Ultra-High Photothermal Conversion Efficiency for NIR-II Photo-Immunotherapy of Metastatic Tumor.

Massive efforts have been concentrated on the advance of eminent near-infrared (NIR) photothermal materials (PTMs) in the NIR-II window (1000-1700 nm), especially organic PTMs because of their intrinsic biological safety compared with inorganic PTMs. However, so far, only a few NIR-II-responsive organic PTMs was explored, and their photothermal conversion efficiencies (PCEs) still remain relatively low. Herein, donor-acceptor conjugated diradical polymers with open-shell characteristics are explored for synergistically photothermal immunotherapy of metastatic tumors in the NIR-II window. By employing side-chain regulation, the conjugated diradical polymer TTB-2 with obvious NIR-II absorption was developed, and its nanoparticles realize a record-breaking PCE of 87.7% upon NIR-II light illustration. In vitro and in vivo experiments demonstrate that TTB-2 nanoparticles show good tumor photoablation with navigation of photoacoustic imaging in the NIR-II window, without any side-effect. Moreover, by combining with PD-1 antibody, the pulmonary metastasis of breast cancer is high-effectively prevented by the efficient photo-immunity effect. Thus, this study explores superior PTMs for cancer metastasis theranostics in the NIR-II window, offering a new horizon in developing radical-characteristic NIR-II photothermal materials.

pH-Responsive NIR-II phototheranostic agents for in situ tumor vascular monitoring and combined anti-vascular/photothermal therapy.

Developing nanoplatforms integrating superior fluorescence imaging ability in second near-infrared (NIR-II) window and tumor microenvironment responsive multi-modal therapy holds great potential for real-time feedback of therapeutic efficacy and optimizing tumor inhibition. Herein, we developed a pH-sensitive pyrrolopyrrole aza-BODIPY-based amphiphilic molecule (PTG), which has a balanced NIR-II fluorescence brightness and photothermal effect. PTG is further co-assembled with a vascular disrupting agent (known as DMXAA) to prepare PTDG nanoparticles for combined anti-vascular/photothermal therapy and real-time monitoring of the tumor vascular disruption. Each PTG molecule has an active PT-3 core which is linked to two PEG chains via pH-sensitive ester bonds. The cleavage of ester bonds in the acidic tumor environment would tricker releases of DMXAA for anti-vascular therapy and further assemble PT-3 cores into micrometer particles for long term monitoring of the tumor progression. Furthermore, benefiting from the high brightness in the NIR-II region (119.61 M-1 cm-1) and long blood circulation time (t1/2 = 235.6 min) of PTDG nanoparticles, the tumor vascular disrupting process can be in situ visualized in real time during treatment. Overall, this study demonstrates a self-assembly strategy to build a pH-responsive NIR-II nanoplatform for real-time monitoring of tumor vascular disruption, long-term tracking tumor progression and combined anti-vascular/photothermal therapy.

Organic Optoelectronic Materials: A Rising Star of Bioimaging and Phototherapy.

Recently, many organic optoelectronic materials (OOMs), especially those used in organic light-emitting diodes (OLEDs), organic solar cells (OSCs), and organic field-effect transistors (OFETs), are explored for biomedical applications including imaging and photoexcited therapies. In this review, recently developed OOMs for fluorescence imaging, photoacoustic imaging, photothermal therapy, and photodynamic therapy, are summarized. Relationships between their molecular structures, nanoaggregation structures, photophysical mechanisms, and properties for various biomedical applications are discussed. Mainly four kinds of OOMs are covered: thermally activated delayed fluorescence materials in OLEDs, conjugated small molecules and polymers in OSCs, and charge-transfer complexes in OFETs. Based on the OOMs unique optical properties, including excitation light wavelength and exciton dynamics, they are respectively exploited for suitable biomedical applications. This review is intended to serve as a bridge between researchers in the area of organic optoelectronic devices and those in the area of biomedical applications. Moreover, it provides guidance for selecting or modifying OOMs for high-performance biomedical uses. Current challenges and future perspectives of OOMs are also discussed with the hope of inspiring further development of OOMs for efficient biomedical applications.

Anti-Quenching NIR-II J-Aggregates of Benzo[c]thiophene Fluorophore for Highly Efficient Bioimaging and Phototheranostics.

Molecular fluorophores with the second near-infrared (NIR-II) emission hold great potential for deep-tissue bioimaging owing to their excellent biocompatibility and high resolution. Recently, J-aggregates are used to construct long-wavelength NIR-II emitters as their optical bands show remarkable red shifts upon forming water-dispersible nano-aggregates. However, their wide applications in the NIR-II fluorescence imaging are impeded by the limited varieties of J-type backbone and serious fluorescence quenching. Herein, a bright benzo[c]thiophene (BT) J-aggregate fluorophore (BT6) with anti-quenching effect is reported for highly efficient NIR-II bioimaging and phototheranostics. The BT fluorophores are manipulated to have Stokes shift over 400 nm and aggregation-induced emission (AIE) property for conquering the self-quenching issue of the J-type fluorophores. Upon forming BT6 assemblies in an aqueous environment, the absorption over 800 nm and NIR-II emission over 1000 nm are boosted for more than 41 and 26 folds, respectively. In vivo visualization of the whole-body blood vessel and imaging-guided phototherapy results verify that BT6 NPs are excellent agent for NIR-II fluorescence imaging and cancer phototheranostics. This work develops a strategy to construct bright NIR-II J-aggregates with precisely manipulated anti-quenching properties for highly efficient biomedical applications.

Innovative probes with aggregation-induced emission characteristics for sensing gaseous signaling molecules.

Diseases are often accompanied by abnormal expression of gaseous signaling molecules including nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S). Sensing these gaseous markers is thus important for identification and investigation of pathological processes. In contrast to conventional approaches, such as electrochemical, chromatographical methods, etc., optical imaging shows merits including high sensitivity, good spatiotemporal resolution, and ideal selectivity. Especially, optical molecular probes with aggregation-induced emission (AIE) properties have good potential for bio-detection since they show maintained optical signals in the aggregated state. Recently, many AIE molecular probes have been developed for imaging disease-related gaseous signaling molecules. Generally, these probes recognize the analytes through turn-on or ratiometric approaches. This review summarizes the recent progress in organic probes with AIE properties for sensing gaseous markers and relative disease diagnosis applications. Based on the types of analytes, the probes are divided into three groups: NO, CO and H2S sensors. Molecular designs and sensing mechanisms of these AIE probes are highlighted. Their gaseous signaling molecules detection applications at cellular and animal levels are presented. Finally, some existing problems and future promising development directions are discussed with the hope to inspire further developments of AIE probes for precise disease diagnosis.

Bright Near-Infrared π-Conjugated Oligomer Nanoparticles for Deep-Brain Three-Photon Microscopy Excited at the 1700 nm Window in Vivo.

The development of three-photon fluorophores with 1700 nm excitation is pressingly desirable for in vivo imaging of tissue resided deep inside the brain. Herein, we report a designed and synthesized fluorescent molecule (OFET) for in vivo mouse brain imaging with three-photon microscopy at a record imaging depth. The OFET molecule has a relatively high fluorescence brightness and has a near-infrared (NIR) maximum emission at 820 nm after integrating as water-dispersible nanoparticles (OEFT NPs). Under 1720 nm excitation, OFET NPs show a large three-photon action cross-section of 1.06 × 10-82 cm6 s2/photon2, which is more than twice that of the commonly used sulforhodamine 101 (SR101) dye. Benefiting from the high tissue penetration depths for both the long excitation in the second NIR window of 1720 nm and the emission wavelength in the first NIR window of 820 nm, a high brightness, and a large action cross-section of three-photon, OFET NPs have good deep-brain imaging performance. Brain vasculatures of a mouse located at a depth of 1696 µm can be clearly resolved in vivo. With no observable cytotoxicity even in a high concentration, the present OFET NPs suggest that fluorescent π-conjugated oligomers are of great potential in high-resolution 3PM imaging of in vivo deep-tissue.

Self-carried nanodrug (SCND-SIS3): A targeted therapy for lung cancer with superior biocompatibility and immune boosting effects.

Transforming growth factor ß (TGF-ß) is a well-known key mediator for the progression and metastasis of lung carcinoma. However, cost-effective anti-TGF-ß therapeutics for lung cancer remain to be explored. Specifically, the low efficacy in drug delivery greatly limits the clinical application of small molecular inhibitors of TGF-ß. In the present study, specific inhibitor of Smad3 (SIS3) is developed into a self-carried nanodrug (SCND-SIS3) using the reprecipitation method, which largely improves its solubility and bioavailability while reduces its nephrotoxicity. Compared to unmodified-SIS3, SCND-SIS3 demonstrates better anti-cancer effects through inducing tumor cell apoptosis, inhibiting angiogenesis, and boosting NK cell-mediated immune responses in syngeneic Lewis Lung Cancer (LLC) mouse model. Better still, it could achieve comparable anti-cancer effect with just one-fifth the dose of unmodified-SIS3. Mechanistically, RNA-sequencing analysis and cytokine array results unveil a TGF-ß/Smad3-dependent immunoregulatory landscape in NK cells. In particular, SCND-SIS3 promotes NK cell cytotoxicity by ameliorating Smad3-mediated transcriptional inhibition of Ndrg1. Furthermore, improved NK cell cytotoxicity by SCND-SIS3 is associated with higher expression of activation receptor Nkp46, and suppressed levels of Trib3 and TSP1 as compared with unmodified-SIS3. Taken together, SCND-SIS3 possesses superior anti-cancer effects with enhanced bioavailability and biocompatibility, therefore representing as a novel therapeutic strategy for lung carcinoma with promising clinical potential.

A NIR molecular rotor photosensitizer for efficient PDT and synchronous mitochondrial viscosity imaging.

Herein, two mitochondria-targeting photosensitizers (PSs, CCVJ-Mito-1 and CCVJ-Mito-2) that exhibit a turn-on fluorescence response towards increasing viscosity are reported. Notably, CCVJ-Mito-2 exhibits absorption in the near-infrared (NIR) region, and can be employed as a NIR PS targeting mitochondria and a fluorescent probe for tracking mitochondrial viscosity changes during photodynamic therapy (PDT). This dual functional PS can help to shed light on the dynamic changes of the cellular microenvironment during PDT and further guide the PDT process.

Molecular Programming of NIR-IIb-Emissive Semiconducting Small Molecules for In Vivo High-Contrast Bioimaging Beyond 1500 nm.

Materials with long-wavelength second near-infrared (NIR-II) emission are highly desired for in vivo dynamic visualizating of microstructures in deep tissues. Herein, by employing an atom-programming strategy, a series of highly fluorescent semiconducting oligomers (SOMs) with tunable NIR-IIb emissions are developed for bioimaging applications. After self-assembly into nanoparticles (NPs), they show good brightness, high photostability, and satisfactory biocompatibility. The SOM NPs are applied as probes for high-resolution imaging of whole-body and hind-limb blood vessels, biliary tract, and bladder with their emissions over 1500 nm. This work demonstrates an atom-programming strategy for constructing semiconducting small molecules with enhanced NIR-II fluorescence for deep-tissue imaging, affording new insight for advancing molecular design of NIR-II fluorophores.

An Activatable NIR Probe for the Detection and Elimination of Senescent Cells.

Cellular senescence is involved in diverse physiological processes. Accumulation of senescent cells can lead to numerous age-related diseases. Therefore, it is of great significance to develop chemical tools to effectively detect and eliminate senescent cells. Till date, a dual functional probe that could detect and eliminate senescent cells has yet been accomplished. Herein, a ß-gal-activated probe, MB-ßgal, based on the methylene blue (MB) fluorophore, was designed to detect and eliminate senescent cells. In the absence of ß-gal, the probe showed no fluorescence and its 1O2 production efficiency was suppressed simultaneously. On the other hand, MB-ßgal could be specifically activated by the high level of ß-gal in senescent cells, thus, releasing free MB with near-infrared (NIR) fluorescence and high 1O2 production efficiency under light irradiation. MB-ßgal demonstrated a fast response, high sensitivity, and high selectivity in detecting ß-gal in an aqueous solution and was further applied to visualization and ablation of senescent cells. As a proof of concept, the dual functions of MB-ßgal were successfully demonstrated in senescent HeLa cells and mouse embryonic fibroblast cells.

Amplifying Free Radical Generation of AIE Photosensitizer with Small Singlet-Triplet Splitting for Hypoxia-Overcoming Photodynamic Therapy.

Type-I photodynamic therapy (PDT) with less oxygen consumption shows great potential for overcoming the vicious hypoxia typically observed in solid tumors. However, the development of type-I PDT is hindered by insufficient radical generation and the ambiguous design strategy of type-I photosensitizers (PSs). Therefore, developing highly efficient type-I PSs and unveiling their structure-function relationship are still urgent and challenging. Herein, we develop two phenanthro[9,10-d]imidazole derivatives (AQPO and AQPI) with aggregation-induced emission (AIE) characteristics and boost their reactive oxygen species (ROS) generation efficiency by reducing singlet-triplet splitting (ΔEST). Both AQPO and AQPI show ultrasmall ΔEST values of 0.09 and 0.12 eV, respectively. By incorporating electron-rich anisole, the categories of generated ROS by AIE PSs are changed from type-II (singlet oxygen, 1O2) to type-I (superoxide anion radical, O2•- and hydroxyl radical, •OH). We demonstrate that the assembled AQPO nanoparticles (NPs) achieve a 3.2- and 2.9-fold increase in the O2•- and •OH generation efficiencies, respectively, compared to those of AQPI NPs (without anisole) in water, whereas the 1O2 generation efficiency of AQPO NPs is lower (0.4-fold) than that of AQPI NPs. The small ΔEST and anisole group endow AQPO with an excellent capacity for type-I ROS generation. In vitro and in vivo experiments show that AQPO NPs achieve an excellent hypoxia-overcoming PDT effect by efficiently eliminating tumor cells upon white light irradiation with good biosafety.

Near-Infrared Thermally Activated Delayed Fluorescence Nanoparticle: A Metal-Free Photosensitizer for Two-Photon-Activated Photodynamic Therapy at the Cell and Small Animal Levels.

Thermally activated delayed fluorescence (TADF) materials with extremely small singlet-triplet energy offsets have opened new horizons for the development of metal-free photosensitizers for photodynamic therapy (PDT) in recent years. However, the exploration of near-infrared (NIR) TADF emitters for efficient two-photon-excited (TPE) PDT is still a formidable challenge, thus it has not been reported yet. In this study, purely organic photosensitizers (PSs) based on the TADF nanoparticles (NIR-TADF NPs) are designed for efficient TPE-PDT, which show excellent singlet oxygen generation ability. Thanks to the intrinsic two-photon excitation and NIR emission characteristics, the NIR-TADF NPs demonstrate promising potential in both single-photon-excited (SPE) and TPE NIR imaging. More importantly, the anti-tumor efficiency and biosafety of TADF-based PSs at the small animal level are confirmed in A549 tumor xenograft models under TPE laser irradiance, which will facilitate the practical biomedical applications of TADF materials. This work not only provides a promising strategy to develop metal-free PSs, but also expands the applied scope of TADF-based nanotherapeutics and advances their possible clinical translation in cancer therapy.

Marriage of 2D Covalent-Organic Framework and 3D Network as Stable Solar-Thermal Still for Efficient Solar Steam Generation.

In this work, a diketopyrrolopyrrole-based 2D covalent-organic framework (COF) is realized and featured with broadband optical absorption and high solar-thermal conversion performance. Moreover, a 3D hierarchical structure, referred to as COF-based hierarchical structure (COFHS), is rationally designed to achieve an enhanced photothermal conversion efficiency. In this water evaporator, diketopyrrolopyrrole is immobilized into conjugated COF to achieve enhanced light absorption, whereas a porous PVA network scaffold is utilized to support COF sheets as well as to enhance the hydrophilicity of the evaporator. Due to this structural advantage, COFHS displays a high solar-to-vapor energy conversion efficiency of 93.2%. Under 1 sun AM1.5 G irradiation, a stable water evaporation rate of 2.5 kg m-2 h-1 can be achieved. As a proof-of-concept application, a water collection device prepared with the COFHS can achieve high solar-thermal water collection efficiency of 10.2 L m-2 d-1 under natural solar irradiation. The good solar-thermal conversion properties and high-water evaporation rate make the COFHS a promising platform for solar-thermal water production.

Recent Advances in Hypoxia-Overcoming Strategy of Aggregation-Induced Emission Photosensitizers for Efficient Photodynamic Therapy.

Hypoxia is an inherent physiologic barrier in the microenvironment of solid tumor and has badly restricted the therapeutic effect of photodynamic therapy (PDT). Meanwhile, the photosensitizer (PS) agents used for PDT applications regularly encounter the tiresome aggregation-caused quenching effect that seriously decreases the production efficiency of cytotoxic reactive oxygen species. The aggregation-induced emission (AIE) PSs with antiquenching characteristics in the aggregate state are considered as a promising tool for achieving highly efficient PDT applications, and plenty of studies have widely demonstrated their advantages in various diseases. Herein, the recent progress of AIE PSs in the battle of antitumor hypoxia issue is summarized and the practical molecular principles of hypoxia-overcoming AIE PSs are highlighted. According to the hypoxia-overcoming mechanism, these representative cases are divided into low O2 -dependent (type I PDT) and O2 -dependent tactics (mainly including O2 -enrichment type II PDT and combination therapy). Furthermore, the underlying challenges and prospects of AIE PSs in hypoxia-overcoming PDT are proposed and thus expect to promote the next development of AIE PSs.

DTX@VTX NPs synergy PD-L1 immune checkpoint nanoinhibitor to reshape immunosuppressive tumor microenvironment for enhancing chemo-immunotherapy.

Immunosuppressed tumor microenvironment (TME) is a major cause of the low response rate in solid tumor patients during PD-1/PD-L1 checkpoint blockade therapy. In this study, a series of small molecule nanomedicines with a 100% drug loading rate were prepared via the nanoprecipitation method. They were used in synergistic chemo-immunotherapy for 4T1 tumors. Among four PD-L1 small-molecule nanoinhibitors, BMS-1 NP with the best anti-tumor performance was selected to replace the therapeutic PD-L1 antibody. The core-shell small-molecule nanomedicine DTX@VTX NP (DTX: Docetaxel and VTX: VTX-2337 or Motolimod) was used to reverse immunosuppressed TME through the depletion of myeloid-derived suppressor cells (MDSCs) and the polarization of macrophages from an M2-like phenotype to M1-like phenotype. Thus, the frequency of cytotoxic CD8+ T cells was significantly increased, resulting in an effective attack on cancer cells. Combining BMS-1 NPs with DTX@VTX NPs, synergistic chemo-immunotherapy of 4T1 tumors was performed, and the results indicate that the inhibition rates of primary and rechallenge tumors achieved 90.5% and 94.3%, respectively. These results indicate that DTX@VTX NPs can synergize PD-L1 nanoinhibitor BMS-1 NPs to reshape the immunosuppressive tumor microenvironment for enhancing the anti-tumor effect of chemo-immunotherapy for breast.

Photochemical Synthesis of Nonplanar Small Molecules with Ultrafast Nonradiative Decay for Highly Efficient Phototheranostics.

There has been much recent progress in the development of photothermal agents (PTAs) for biomedical and energy applications. Synthesis of organic PTAs typically involves noble metal catalysts and high temperatures. On the other hand, photochemical synthesis, as an alternative and green chemical technology, has obvious merits such as low cost, energy efficiency, and high yields. However, photochemical reactions have rarely been employed for the synthesis of PTAs. Herein, a facile and high-yield photochemical reaction is exploited for synthesizing nonplanar small molecules (NSMs) containing strong Michler's base donors and a tricyanoquinodimethane acceptor as high-performance PTAs. The synthesized NSMs show interesting photophysical properties including good absorption for photons of over 1000 nm wavelength, high near-infrared extinction coefficients, and excellent photothermal performance. Upon assembling the NSMs into nanoparticles (NSMN), they exhibit good biocompatibility, high photostability, and excellent photothermal conversion efficiency of 75%. Excited-state dynamic studies reveal that the NSMN has ultrafast nonradiative decay after photoexcitation. With these unique properties, the NSMN achieves efficient in vivo photoacoustic imaging and photothermal tumor ablation. This work demonstrates the superior potential of photochemical reactions for the synthesis of high-performance molecular PTAs.

Multi-Synergistic Removal of Low-Boiling-Point Contaminants with Efficient Carbon Aerogel-Based Solar Purifier.

Solar steam generation is considered as an efficient way for addressing water shortage issues via seawater desalination and wastewater purification. In a solar evaporator, an absorber would convert optical energy to heat for evaporating nearby water. In this process, many low-boiling-point contaminants can also be evaporated along with water steam, which compromises the effectiveness of purification. There is, so far, no study on the removal of such low-boiling-point contaminants such as organic pesticides in wastewater. To address this problem, we demonstrate a versatile carbon hybrid aerogel (CHA) as a solar powered water purification platform. With an elaborate absorber design, the maximum solar evaporation rate of 2.1 kg m-2 h-1 is achieved under 1 sun illumination. More importantly, CHA can effectively suppress the evaporation of low-boiling-point contaminants including common pesticides and mercury ion via its strong adsorption and retention effect. Synergetic steaming and the adsorption of CHA will inspire more paradigms of solar steam generation technologies for applications relevant to detoxification and water remediation.

Aligned Millineedle Arrays for Solar Power Seawater Desalination with Site-Specific Salt Formation.

As a sustainable and clean water production technology, solar thermal water evaporation has been extensively studied in the past few years. One challenge is that upon operation, salt would form on surface of the solar absorbers leading to inefficient water supply and light absorption and thus much reduced water vaporization rate. To address this problem, a simple solar evaporator based on an array of aligned millineedles for efficient solar water evaporation and controlled site-specific salt formation is demonstrated. The maximum solar evaporation rate achieved is 2.94 kg m-2 h-1 under one Sun irradiation in brine of high salinity (25 wt% NaCl), achieving energy conversion efficiency of 94.5% simultaneously. More importantly, the spontaneously site-specific salt formation on the tips of millineedles endows this solar evaporator with salt harvesting capacity. Rationally separating the clean water and salt from brine by condensation and gravity assistance, this tip-preferential crystallization solar evaporator is not affected by the salt clogging compared with conventional 2D solar evaporators. This study provides new insights on the design of solar evaporators and advances their applications in sustainable seawater desalination and wastewater management.

Iron Self-Boosting Polymer Nanoenzyme for Low-Temperature Photothermal-Enhanced Ferrotherapy.

In this work, an iron self-boosting polymer nanoenzyme was prepared by using pyrrole-3-carboxylic acid as a monomer and iron as an oxidizing agent via a simple and one-step method [hereafter referred to as FePPy nanoparticles (NPs)]. In fact, researchers previously paid negligible attention on the iron element during the polymerization reaction of polypyrrole, thus the intrinsically catalytic functions and enzymatic activities of the high iron content (wt %: 21.11%) are ignored and not fully explored. As expected, results demonstrate that the as-synthesized FePPy NPs can decompose H2O2 to generate hydroxyl radicals (•OH) which exhibit enzyme characteristics, further inducing a nonapoptotic ferroptosis pathway. Moreover, the nanoenzyme shows impressive photothermal properties which can accelerate the Fenton reactions to enhance ferroptosis. The combined photothermal and ferroptosis therapy of FePPy NPs was found to have high efficacy. With the properties of easy synthesis, high efficacy, and good biocompatibility, the FePPy NPs are considered as potential agents for cancer treatments.