Excellent Photodynamic Therapy Research Articles

Aqueous Topological Synthesis of Au@semiconductor Core-Shell Nanocrystals with Morphology and Composition Engineering.

Core-shell nanocrystals (C-S NCs) are an essential class of materials whose structural engineering has attracted wide attention due to their tunable optical and electrical properties, especially noble metal@semiconductor (NMS) C-S NCs with flexible plasmon-exciton coupling. Due to their diverse critical applications, especially aqueous biological applications, herein we propose an aqueous topological strategy enabled by cation exchange reactions (CER) to synthesize various plasmonic Au@semiconductor C-S NCs, in which environmentally friendly triphenylphosphine (TPP) is used as an initiator instead of inflammable tributyl phosphine (TBP). The introduction of the milder, solid TPP facilitated a new aqueous CER strategy for synthesizing Au@semiconductor NCs with tailored chalcogenide compositions and morphologies. For example, the as-synthesized Au@ZnS C-S NRs had better absorption and biocompatibility and exhibited excellent photodynamic therapy efficacy.

Enriched photosensitizer for deep-seated-tumor photodynamic therapy

Photodynamic therapy (PDT) is an innovative approach that utilizes photochemical reactions for non-invasive disease treatment. Conventional PDT is limited by the low penetration depth of visible light required for activation. Herein, we employed upconversion nanoparticles (UCNPs) to extend the activation wavelength of photosensitizers into the infrared range, enabling a treatment depth of over 10 mm. Furthermore, we also used the abundant amino groups of branched polyethyleneimine (PEI) with spatial structure to enhance the loading capacity of protoporphyrin (PPIX), and we ultimately improved skin tumor clearance rates. Moreover, we achieved tumor-specific treatment by utilizing folic acid (FA) targeting and active enrichment of PPIX. According to cellular experimental results, we demonstrated the remarkable reactive oxygen species generation capability of the material and ultra-low dark toxicity. Additionally, we investigated the apoptosis mechanism and demonstrated that the synthesized nanoparticle stimulates the up-regulation of apoptosis-associated proteins Bax/Bcl-2 and Cyto c. During in vivo experiments involving intravenous injection in mouse tails, we investigated the anticancer efficacy of the nanoparticle, confirming its excellent PDT effects. This research provides a promising avenue for future non-invasive treatment of deep-seated tumors, offering a method for the treatment and management of specific cancers.

Novel near-infrared BODIPY-cyclodextrin complexes for photodynamic therapy

To meet the requirements of diagnosis and treatment, photodynamic therapy (PDT) is a promising cancer treatment with less side-effect. A series of novel BODIPY complexes (BODIPY-CDs) served as PDT agents were first reported to enhance the biocompatibility and water solubility of BODIPY matrix through the click reaction of alkynyl-containing BODIPY and azide-modified cyclodextrin (CD). BODIPY-CDs possessed superior water solubility due to the introduction of CD and their fluorescence emission apparently redshifted (>90 nm) on account of triazole units as the linkers compared to alkynyl-containing BODIPY. Moreover, all the BODIPY-CDs were no cytotoxicity toward NIH 3T3 in different drug concentrations from 12.5 to 200 μg/mL, and had a certain inhibitory effect on tumor HeLa cells. Particularly, BODIPY-β-CD exhibited high reactive oxygen species generation and excellent photodynamic therapy activity against HeLa cells compared to other complexes. The cell viability of BODIPY-β-CD was dramatically reduced up to 20% in the concentration of 100 μg/mL upon 808 nm laser irradiation. This architecture might provide a new opportunity to develop valuable photodynamic therapy agents for tumor cells.

Long-wavelength absorbing and mitochondria or lysosome organelle-targeting photosensitizers with flexible or rigid terminus for fluorescence imaging and high-performance photodynamic therapy

In this study, two chlorin photosensitizers (PSs) having long-wavelength absorbing (λmax 707 and 709 nm) and mitochondria or lysosome organelle-targeting abilities have been developed for use in photodynamic therapy (PDT). We simply modified two PSs, PS1 (N-propyl unit as a flexible terminus) and PS2 (N-propargyl unit as a rigid terminus), which displayed near-infrared absorption and fluorescence emission and high 1O2 quantum yield (0.720 and 0.593), indicating a suitable PS for PDT, resulting in high-performance photodynamic activity with low IC50 values (0.31–0.36 μM against A549 and HeLa cells). Importantly, PS1 and PS2 exhibited excellent mitochondrial or lysosomal organelle-targeting ability with high Pearson's correlation coefficient values (∼0.9). The excellent PDT effect of PS1 and PS2 was confirmed by fluorescence images of intracellular reactive oxygen species generation as well as live/dead staining images. Therefore, these two PSs have great potential as fluorescence imaging materials and PDT reagents.

Combining Multiple Photosensitizer Modules into One Supramolecular System for Synergetic Enhanced Photodynamic Therapy.

Photodynamic therapy (PDT), as an emerging cancer treatment, requires the development of highly desirable photosensitizers (PSs) with integrated functional groups to achieve enhanced therapeutic efficacy. Coordination-driven self-assembly (CDSA) would provide an alternative approach for combining multiple PSs synergistically. Here, we demonstrate a simple yet powerful strategy of combining conventional chromophores (tetraphenylethylene, porphyrin, or Zn-porphyrin) with pyridinium salt PSs together through condensation reactions, followed by CDSA to construct a series of novel metallo-supramolecular PSs (S1-S3). The generation of reactive oxygen species (ROS) is dramatically enhanced by the direct combination of two different PSs, and further reinforced in the subsequent ensembles. Among all the ensembles, S2 with two porphyrin cores shows the highest ROS generation efficiency, specific interactions with lysosome, and strong emission for probing cells. Moreover, the cellular and living experiments confirm that S2 has excellent PDT efficacy, biocompatibility, and biosafety. As such, this study will enable the development of more efficient PSs with potential clinical applications.

Dual-Responsive hollow mesoporous organosilicon nanocarriers for photodynamic therapy

Hypothesis: The nano-delivery platform, -SS-HMONs@MB@MnO2 nanoparticles (SMM NPs) loaded with methylene blue (MB) as photosensitizer have excellent photodynamic therapy (PDT) effect. The disulfide bond and MnO2 give the shell redox-responsive properties. SMM NPs consume glutathione (GSH) in tumor cells, reducing the scavenging of reactive oxygen species (ROS) by GSH and enhancing the PDT effect of MB.Experiments: The GSH dual-responsive nano-delivery platform, was designed and constructed by using disulfide-doped hollow mesoporous organosilicon nanoparticles (-SS-HMONs) as intermediate responsive layer, loaded with MB as photosensitizer and coated with MnO2 as shells. The MB photosensitizer release and GSH response were characterized. The PDT effect of nanoparticles was evaluated.Findings: The SMM NPs were uniform in size and well dispersed. The nanoparticles could react with GSH, leading to the decomposition of MnO2 shells and the breakage of disulfide bonds in -SS-HMONs, resulted in the release of MB photosensitizer. The cell experiment showed that SMM NPs had good ROS generating ability and PDT effect after being sucked by tumor cells, which could effectively kill tumor cells. However, in vivo experiments demonstrated that SMM NPs showed slight inhibition on tumor growth. The actual effect in animals was different from the effect in cells.

Integration of O2-economised tumour-targeted photosensitive magnetic nanomaterials in the diagnosis and therapy of gastric cancer.

Hypoxia in the tumour microenvironment is a major limiting factor in photodynamic therapy. The present study employed a novel O2-economised photosensitizer, ACSN, to effectively curtail oxygen consumption by impeding the aerobic respiration of tumour cells, thereby increasing the reactive oxygen species (ROS) production in photodynamic therapy. To enhance the efficacy of photodynamic therapy, the active targeting peptide iRGD was employed to facilitate drug accumulation in the tumour tissue. Therefore, we constructed a targeted drug platform, ACSN/Fe3O4@MSNs-iRGD, that integrates diagnosis and treatment. The drug exhibited excellent active targeting ability towards gastric cancer MGC-803 cells and can efficiently penetrate the mitochondria upon cellular internalisation. The photosensitizer ACSN, released from the drug, effectively suppressed mitochondrial aerobic respiration to conserve oxygen and exhibited robust ROS production upon laser excitation. The core-shell structure comprises Fe3O4, which offers excellent T2 dark contrast for real-time tumour monitoring through MRI imaging. By incorporating excellent photodynamic therapy and MRI imaging capabilities, this drug can serve as an effective platform for the integration of tumour diagnosis and treatment, thus addressing the limitations associated with conventional tumour therapies. It is anticipated that this approach will soon be clinically translated.

The Balance Effect of π-π Electronic Coupling on NIR-II Emission and Photodynamic Properties of Highly Hydrophobic Conjugated Photosensitizers.

Deep NIR organic phototheranostic molecules generally have large π-conjugation structures and show highly hydrophobic properties, thus, forming strong π-π stacking in the aqueous medium, which will affect the phototheranostic performance. Herein, an end-group strategy is developed to lift the performance of NIR-II emitting photosensitizers. Extensive characterizations reveal that the hydrogen-bonding interactions of the hydroxyl end group can induce a more intense π-π electronic coupling than the chlorination-mediated intermolecular forces. The results disclose that π-π stacking will lower fluorescence quantum yield but significantly benefit the photodynamic therapy (PDT) efficiency. Accordingly, an asymmetrically substituted derivative (BTIC-δOH-2Cl) is developed, which shows balanced phototheranostic properties with excellent PDT efficiency (14.6 folds of ICG) and high NIR-II fluorescence yield (2.27%). It proves the validity of the end-group strategy on controlling the π-π interactions and rational tuning the performance of NIR-II organic phototheranostic agents.

Asymmetric A‐DA′D‐A′′ Molecular Configuration Type‐I Photosensitizer with Two Complementary Reactive Oxygen Species for Efficient Imaging and Photodynamic Therapy

AbstractType‐I photosensitizers (PSs) can efficiently generate reactive oxygen species (ROS) in the hypoxia condition of tumors, which show less oxygen dependence and are considered better candidates for photodynamic therapy (PDT). However, relatively few efficient type‐I organic PSs simultaneously generating two or more type‐I ROS under irradiation are reported. Herein, new alternate donor (D)‐acceptor (A) type molecules containing ladder‐type core (DA′D) fused with an electron‐deficient benzothiadiazole core are reported, which show symmetrical A‐DA′D‐A (QY1) and asymmetrical A‐DA′D‐A′′ (QY2) configurations, respectively. As these ROSs possess complementary properties of strong oxidizing ability (•OH) and long radical lifetime (O2•−), in vitro and in vivo experiments demonstrate that QY1 and QY2 show excellent PDT effects for tumor cells under normoxia or hypoxia, and can achieve remarkable tumor growth inhibition (TGI) rate of 90% for the QY2. More importantly, the generation of •OH in these PSs is revealed by experiments both in aqueous and in vitro, including the well‐known transformation of O2•− and direct electron transition from water to excited triplet PS. It thus provides a comprehensive understanding of the O2 dependence property of •OH radical and deep insights into the mechanism of type‐I PS.

Mn2+ /Ir3+ -Doped and CaCO3 -Covered Prussian Blue Nanoparticles with Indocyanine Green Encapsulation for Tumor Microenvironment Modulation and Image-Guided Synergistic Cancer Therapy.

The development of smart theranostic nanoplatforms has gained great interest in effective cancer treatment against the complex tumor microenvironment (TME), including weak acidity, hypoxia, and glutathione (GSH) overexpression. Herein, a TME-responsive nanoplatform named PMICApt /ICG, based on PB:Mn&Ir@CaCO3 Aptamer /ICG, is designed for the competent synergistic photothermal therapy and photodynamic therapy (PDT) under the guidance of photothermal and magnetic resonance imaging. The nanoplatform's aptamer modification targeting the transferrin receptor and the epithelial cell adhesion molecule on breast cancer cells, and the acid degradable CaCO3 shell allow for effective tumor accumulation and TME-responsive payload release in situ. The nanoplatform also exhibits excellent PDT properties due to its ability to generate O2 and consume antioxidant GSH in tumors. Additionally, the synergistic therapy is achieved by a single wavelength of near-infrared laser. RNA sequencing is performed to identify differentially expressed genes, which show that the expressions of proliferation and migration-associated genes are inhibited, while the apoptosis and immune response gene expressions are upregulated after the synergistic treatments. This multifunctional nanoplatform that responds to the TME to realize the on-demand payload release and enhance PDT induced by TME modulation holds great promise for clinical applications in tumor therapy.

A Cascade Strategy Boosting Hydroxyl Radical Generation with Aggregation-Induced Emission Photosensitizers-Albumin Complex for Photodynamic Therapy.

Effective photodynamic therapy (PDT) requires photosensitizers (PSs) to massively generate type I reactive oxygen species (ROS) in a less oxygen-dependent manner in the hypoxia tumor microenvironment. Herein, we present a cascade strategy to boost type I ROS, especially hydroxyl radical (OH·-), generation with an aggregation-induced emission (AIE) photosensitizer-albumin complex for hypoxia-tolerant PDT. The cationic AIE PS TPAQ-Py-PF6 (TPA = triphenylamine, Q = anthraquinone, Py = pyridine) contains three important moieties to cooperatively enhance free radical generation: the AIE-active TPA unit ensures the effective triplet exciton generation in aggregate, the anthraquinone moiety possesses the redox cycling ability to promote electron transfer, while the cationic methylpyridinium cation further increases intramolecular charge transfer and electron separation processes. Inserting the cationic TPAQ-Py-PF6 into the hydrophobic domain of bovine serum albumin nanoparticles (BSA NPs) could greatly immobilize its molecular geometry to further increase triplet exciton generation, while the electron-rich microenvironment of BSA ultimately leads to OH·- generation. Both experimental and theoretical results confirm the effectiveness of our molecular cationization and BSA immobilization cascade strategy for enhancing OH·- generation. In vitro and in vivo experiments validate the excellent antitumor PDT performance of BSA NPs, superior to the conventional polymeric encapsulation approach. Such a multidimensional cascade strategy for specially boosting OH·- generation shall hold great potential in hypoxia-tolerant PDT and related antitumor applications.

Nanosilver-decorated covalent organic frameworks for enhanced photodynamic, photothermal, and antibacterial properties

Bacterial infections caused by multidrug-resistant bacteria pose an extremely serious treat to human health However, nanoscale antibacterial materials can effectively inhibit bacterial growth without inducing bacterial resistance. Herein, we have developed a highly effective antibacterial agent by immobilizing silver nanoparticles (AgNPs) within a novel covalent organic framework (COF). The COFBDP/CD-S-3-Ag system was synthesized in situ using BODIPY phoyosensitizer (BDP) and carbon quantum dots (CD-S-3) as precursors. The optimized COFBDP/CD-S-3-Ag system exhibited excellent photodynamic therapy (PDT) and photothermal therapy (PTT). Importantly, the COFBDP/CD-S-3-Ag system, with many active groups, can capture and kill bacteria effectively by interacting with them, thereby contributing to improved antibacterial efficacy. As expected, the designed COFBDP/CD-S-3-Ag system combines the advantages of COFBDP/CD-S-3 (preventing the aggregation of AgNPs and having the ability to capture bacteria) and AgNPs (antibacterial ability), demonstrating excellent antibacterial efficacy. This study developed a new class of antibacterial materials and took an important step forward in promoting the application of COF-based antibacterial materials.

Type-I organic photosensitizers with two complementary reactive oxygen species based on donor-acceptor (D-A) molecules

Type-I photosensitizers (PSs) are considered to be a better choice for photodynamic therapy (PDT) because they can efficiently generate reactive oxygen species (ROS) in the hypoxia condition of tumor, showing less oxygen dependence. However, there are relatively few reported highly efficient type-I organic PSs, especially those simultaneously generated two or more species of type-I ROS. Herein, based on electron-acceptor of 9,10-phenanthrenequinone (PQ), a D-A-D structural type-I PS of PPQ constructed from electron-donor of 9-phenyl-carbazole (PCZ) was firstly developed and could simultaneously produce two type-I ROS under white light irradiation. As the generated ROS of hydroxyl radical (•OH) and superoxide anion radical (O2•−) possessed complementary oxidizing ability and radical lifetime, PPQ showed excellent PDT effects for tumor cells under normoxia or hypoxia. The ability of ROS generation and PDT performance of PPQ were better than those of another PQ derivative (TPQ) constructed with common electron-donor triphenylamine (TPA). More importantly, experiments in aqueous solution and vitro both revealed that •OH generated not only from the well-known transformation of O2•− but also direct electron transition from water to triplet excited PS, which demonstrated the oxygen dependence of type-I PSs more clearly. This new type-I PS offers an opportunity to obtain deep insights of the mechanism of type-I PSs, and provides a new strategy for development of type-I PSs.

Glycopolymeric Photosensitizers with Cholic Acid for HepG2-Targeted Chemo-Photodynamic Synergistic Therapy.

The aggregation-caused quenching, premature drug release, and hypoxia-caused resistance of photodynamic therapy (PDT) are challenges in the design and preparation of novel porphyrin-containing photosensitizers. In this work, a series of block copolymers consisting of a hydrophilic glycopolymer block and a porphyrin-containing hydrophobic block were prepared via reversible addition-fragmentation chain transfer polymerization. The polymeric photosensitizers generate singlet oxygen and excellent PDT against HepG2, which can be strengthened by the addition of cholic acid. To combine with chemotherapy, doxorubicin (Dox) was successfully loaded into copolymers, which were observed to be more phototoxic, indicating that the therapeutic benefit of the synergistic effect of PDT and chemotherapy is better than their simple combination. The sugar-cell-specific interaction of galactose-containing photosensitizers results in a stronger mean fluorescent index (MFI) intracellular uptake in HepG2 cells in vitro compared to L929 and MCF-7 cells. These polymeric nanoplatforms present a versatile and effective avenue for developing synergistic therapy for cancer treatment.

Ultra-Small Nano-Assemblies as Tumor-Targeted and Renal Clearable Theranostic Agent for Photodynamic Therapy.

It is a challenge to design photosensitizers to balance between the tumor-targeting enrichment for precise treatment and efficient clearance within a reasonable timescale for reducing side effects. Herein, an ultra-small nano-photosensitizer 1a with excellent tumor-specific accumulation and renal clearance is reported. It is formed from the self-assembly of compound 1 bearing three triethylene glycol (TEG) armsand two pyridinium groups in water. The positively charged surface with neutral TEG coating enables 1a to efficiently target the tumor, with the signal-to-background ratio reaching as high as 11.5 after tail intravenous injection. The ultra-small size of 1a with an average diameter of 5.6nm allows its fast clearance through kidney. Self-assembly also endows 1a with an 18.2-fold enhancement of reactive oxygygen species generation rate compared to compound 1 in organic solution. Nano-PS 1a manifests an excellent photodynamic therapy efficacy on tumor-bearing mouse models. This work provides a promising design strategy of photosensitizers with renal clearable and tumor-targeting ability.

Identification of a luminescent platinum(II) complex with BODIPY derivative as novel photodynamic therapy agent for triple negative breast cancer cells

Triple-negative breast cancer (TNBC) is one of the most malignant breast tumors for its poor prognosis and high tumor recurrence. It is urgent to develop new strategy or effective agents to overcome resistance and improve therapeutic effectiveness. Boron-dipyrromethene (BODIPY) based photosensitizers possess exciting photophysical features suitable for theranostic applications, namely, photodynamic therapy (PDT). We have designed a luminescent monofunctional platinum(II) complex with BODIPY derivative, namely I2BC-Pt, as novel high PDT agent against triple negative breast cancer (TNBC). The di-iodinated BODIPY complex I2BC-Pt showed excellent PDT effect against TNBC cells in green light (520 nm) giving IC50 values of 0.11–0.13 μM in MDA-MB-231 and MDA-MB-468 cells. I2BC-Pt predominately aggregated in the mitochondria of MDA-MB-231 cells and emitted green fluorescence. Besides, the anticancer mechanism studies demonstrated that I2BC-Pt could help DNA repair through attenuating RAD51, FoxM1 and BRCA1/2, and induce p53-mediated apoptosis of TNBC cells. Taken together, I2BC-Pt could be potentially developed as a BODIPY-based photosensitizers for TNBC therapy.

Polymer theranostics with multiple stimuli-based activation of photodynamic therapy and tumor imaging.

Background: Efficient theranostic strategies concurrently bring and use both the therapeutic and diagnostic features, serving as a cutting-edge tool to combat advanced cancers. Goals of the Investigation: Here, we develop stimuli-sensitive theranostics consisting of tailored copolymers forming micellar conjugates carrying pyropheophorbide-a (PyF) attached by pH-sensitive hydrazone bonds, thus enabling the tumor microenvironment-sensitive activation of the photodynamic therapy (PDT) effect, fluorescence or phosphorescence. Results: The nanomedicines show superior anti-tumor PDT efficacy and huge tumor-imaging potential, while reducing their accumulation, and potentially side effects, in the liver and spleen. The developed theranostics exhibit clear selective tumor accumulation at high levels in the mouse sarcoma S180 tumor model with almost no PyF found in the healthy tissues after 48 h. Once in the tumor, illumination at λexc = 420 nm reaches the therapeutic effect due to the 1O2 generation. Indeed, an almost complete inhibition of tumor growth is observed up to 18 days after the treatment. Conclusion: The clear benefit of the specific PyF release and activation in the acidic tumor environment for the targeted delivery and tissue distribution dynamics was proved. Conjugates carrying pyropheophorbide-a (PyF) attached by pH-sensitive hydrazone bonds showed their excellent antitumor PDT effect and its applicability as advanced theranostics at very low dose of PyF.

Supramolecular photosensitizers using extended macrocyclic hosts for photodynamic therapy with distinct cellular delivery.

The photosensitizers (PSs) for photodynamic therapy (PDT) mostly possess conjugated skeletons that are over-sized and poorly water-soluble to be encapsulated by conventional macrocyclic receptors. Herein, we report that two fluorescent hydrophilic cyclophanes, AnBox·4Cl and ExAnBox·4Cl, can effectively bind hypocrellin B (HB), a pharmaceutically active natural PS for PDT, with binding constants of the 107 level in aqueous solutions. The two macrocycles feature extended electron-deficient cavities and can be facilely synthesized through photo-induced ring expansions. The corresponding supramolecular PSs (HB⊂AnBox4+ and HB⊂ExAnBox4+) exhibit desirable stability, biocompatibility, and cellular delivery, as well as excellent PDT efficiency against cancer cells. In addition, living cell imaging results indicate that HB⊂AnBox4+ and HB⊂ExAnBox4+ have different delivery effects at the cellular level.

Carbon Dots Derived from Tea Polyphenols as Photosensitizers for Photodynamic Therapy

Photodynamic therapy (PDT) has become an emerging cancer treatment method. Choosing the photosensitizer (PS) compounds is one of the essential factors that can influence the PDT effect and action. Carbon dots (CDs) have shown great potential as photosensitizers in PDT of cancers due to their excellent biocompatibility and high generation of reactive oxygen species (ROS). Here, we used tea polyphenol as raw material for synthesized tea polyphenol carbon dots (T-CDs) that show dual emission bands of red and blue fluorescence and can efficiently generate hydroxyl radicals (OH) under mildly visible irradiation with a LED light (400-500 nm, 15 mW cm-2). The extremely low cytotoxicity and excellent biocompatibility of T-CDs without light irradiation were tested using MTT and hemolytic assay. Further, T-CDs have been shown by in vivo experiments, using a mouse breast cancer cell line (4T1) subcutaneously injected in the back of the mouse buttock as a model, to effectively inhibit the tumor cell proliferation in solid tumors and show an excellent PDT effect. In addition, pathological sections of the mice tissues after further treatment showed that the T-CDs had no apparent impact on the major organs of the mice and did not produce any side effect lesions. This work demonstrates that the as-synthesized T-CDs has the potential to be used as a PS in cancer treatment.

Cardiolipin-Targeted NIR-II Fluorophore Causes "Avalanche Effects" for Re-Engaging Cancer Apoptosis and Inhibiting Metastasis.

Restoring innate apoptosis and simultaneously inhibiting metastasis by a molecular drug is an effective cancer therapeutic approach. Herein, a large rigid and V-shaped NIR-II dye, DUT850, is rationally designed for potential cardiolipin (CL)-targeted chemo-phototheranostic application. DUT850 displays moderate NIR-II fluorescence, excellent photodynamic therapy (PDT) and photothermal therapy (PTT) performance, and ultra-high photostability. More importantly, the unique rigid V-shaped backbone, positive charge, and lipophilicity of DUT850 afford its specific recognition and efficient binding to CL; such an interaction of DUT850-CL induced a spectrum of physiological disruptions, including translocation of cytochrome c, Ca2+ overload, reactive oxygen species burst, and ATP depletion, which not only activated cancer cell apoptosis but also inhibited tumor metastasis both in vitro and in vivo. Furthermore, the tight binding of DUT850-CL improves the phototoxicity of DUT850 toward cancer cells (IC50 as low as 90 nM) under safe 808 nm laser irradiation (330 mW cm-2). Upon encapsulation into bovine serum albumin (BSA), DUT850@BSA exerted a synergetic chemo-PDT-PTT effect on the 4T1 tumor mouse model, eventually leading to solid tumor annihilation and metastasis inhibition, which could be followed in real time with the NIR-II fluorescence of DUT850. This work contributed a promising approach for simultaneously re-engaging cancer cell apoptotic networks and activating the anti-metastasis pathway by targeting a pivotal upstream effector, which will bring a medical boon for inhibition of tumor proliferation and metastasis.