Ferroptosis promotes sonodynamic therapy: a platinum(ii)–indocyanine sonosensitizer

Sonodynamic therapy (SDT) has unique advantages in deep tumour ablation due to its deep penetration depth, showing great preclinical and clinical potential. Herein, a platinum(ii)–cyanine complex has been designed to investigate its potential as a SDT anticancer agent. It generates singlet oxygen (¹O₂) under ultrasound (US) irradiation or light irradiation, and exhibits US-cytotoxicity in breast cancer 4T1 cells but with negligible dark-cytotoxicity. Mechanistic investigations reveal that Pt-Cy reduces the cellular GSH and GPX4, and triggers cancer cell ferroptosis under US irradiation. The metabolomics analysis illustrates that Pt-Cy upon US treatment significantly dysregulates glutathione metabolism, and finally induces ferroptosis. In vivo studies further demonstrate that Pt-Cy inhibits tumor growth under US irradiation and its efficiency for SDT is better than that for PDT in vivo. This is the first example of platinum(ii) complexes for sonodynamic therapy. This work extends the biological applications of metal complexes from PDT to SDT.

A novel platinum(ii)–cyanine complex showed a greater excellent sonodynamic therapeutic effect than photodynamic therapy in vivo. This work expands the biological applications of metal complexes from traditional photodynamic therapy to sonodynamic therapy.     

Effect of polyethylenimine, a cell permeabilizer, on the photosensitized destruction of algae by methylene blue and nuclear fast red

The present study reports the effect a cell permeabilizer, polyethylenimine (PEI) has on the photodynamic effect of methylene blue (MB) and nuclear fast red (NFR) in the presence of hydrogen peroxide (H2O2). The photosensitized destruction of the algae Chlorella vulgaris under irradiation with visible light is examined. The photodynamic effect was investigated under aerobic and anaerobic conditions. The presence of a permeabilizer during the photosensitized destruction of C. vulgaris does not enhance the activity of the MB, MB/H2O2 system or the NFR, NFR/H2O2 system under aerobic conditions. However under anaerobic conditions we have determined that when a cell permeabilizer was added to the MB/H202 system, the photosensitized destruction of C. vulgaris proceeded via a combination of Type I and Type II mechanisms. The presence of PEI enforces MB/H2O2 to be active toward the destruction of C. vulgaris whether oxygen is present or absent. Under aerobic and anaerobic conditions the activity of NFR was suppressed in the presence of PEI as a result of electrostatic interactions between the photosensitizer and the cell permeabilizer. The decrease in fluorescence recorded is indicative of destruction of the chlorophyll a pigment.     

Mitochondria-targeted theranostic nanoparticles for optical sensing of oxygen,photodynamic cancer therapy,and assessment of therapeutic efficacy

We report on a novel kind of mitochondria-targeted theranostic nanoparticles (NPs). The NPs are doped with the oxygen-sensitive probe Pt(II)-porphyrins (PtTFPP) which exerts a dual role in acting as a diagnostic tool that can sense oxygen via quenching of luminescence, but also acts as an agent in photodynamic therapy (PDT) of cancer. In addition, it allows therapeutic efficacy to be assessed in-situ. Upon appropriate high-energy photoirradiation, the NPs generate singlet oxygen by energy transfer from triplet PtTFPP to ground state oxygen, and cell death is induced via PDT. Under low-energy light irradiation, in contrast, the NPs can be utilized to detect oxygen consumption rate via time-resolved luminescence measurements in order to study the efficacy of PDT. This is the first report where a single nanoagent is used to stimulate PDT and also to assess the efficacy of PDT. In our perception, the method provides a promising platform for testing anti-cancer drugs.

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Graphical abstract We report on a kind of mitochondria-targeted theranostic nanoparticles (NPs) doped with Pt(II)-porphyrins for oxygen sensing via quenching of luminescence, efficient photodynamic therapy (PDT) of cancer and quantitative assessment of therapeutic response in-situ.

     

Chromosomes are target sites for photodynamic therapy as demonstrated by subcellular laser microirradiation

The present investigation has been undertaken to examine the possibility that the cell nucleus, and specifically the genetic material, is a target site for photodynamic therapy. PTK2 and Hep-2 cells are pretreated with a medium containing 15 microg/ml (0.09 mM) 5-aminolevulinic acid (ALA). Individual fluorescence images are recorded for each selected cell using a cooled charge-coupled device (CCD). A laser microbeam system generating 630 nm is used for subcellular-region irradiation of specific targets: chromosomes, the mitotic spindle, the perispindle region and the peripheral cytoplasm. Nuclei of interphase cells are also irradiated. Data comparing the sensitivities of the different subcellular microirradiation sites in ALA-treated mitotic cells demonstrate that under the irradiation conditions used, the chromosome is the most sensitive subcellular target followed by the perispindle region, the peripheral cytoplasm and spindle, and, lastly, the interphase nucleus.     

Two-photon photodynamic therapy of C6 cells by means of 5-aminolevulinic acid induced protoporphyrin IX

Photodynamic therapy (PDT) has received increased attention as a treatment modality for malignant tumors as well as non-oncologic diseases such as age-related macular degeneration (AMD). An alternative to excite the photosensitizer by the common one-photon absorption is the method of two-photon excitation (TPE). This two-photon photodynamic therapy has the potential of improving the therapeutic outcome due to a highly localized photodynamic effect. The present study investigated the two-photon excited PDT performing in vitro experiments where C6 rat glioma cells were irradiated with a pulsed and focused fs Ti:sapphire laser emitting light at 800 nm. The irradiance distribution of the laser beam was carefully analyzed before the experiment and the applied irradiance was known for each position within the irradiated cell layer. Cells were divided into four groups and one group was incubated with 5-ALA and irradiated 4-5h later. The survival of this group was tested after irradiation by means of ethidium bromide and acridine orange staining and compared to a control group, which was irradiated under the same conditions, but not incubated with 5-ALA before. Both groups showed necrotic areas depending on the applied irradiance, the value of which at the margin of the necrotic area could be deduced from its size. 5-ALA incubated cells became necrotic after irradiation with a mean irradiance above 6.1 x 10(10) W/cm(2), while non-incubated cells remained viable. Cells of both groups became necrotic when treated with an irradiance above 10.9 x 10(10) W/cm(2). The observed affected area of the cell layers was between 0.13 mm(2) and 1.10 mm(2). Since the irradiation of non-incubated cells below the mean power density of 10.9 x 10(10) W/cm(2) induced no necrosis, apparently no thermal damage was induced in the cells and necrosis of the 5-ALA incubated cells can be ascribed to the photodynamic effect induced by two-photon excitation. The successful photodynamic treatment of a large area of a monolayer cell culture induced by two-photon excitation offers new perspectives for photodynamic treatment modalities.     

Photodynamic studies of metallo 5,10,15,20-tetrakis(4-methoxyphenyl) porphyrin: photochemical characterization and biological consequences in a human carcinoma cell line.

The photodynamic activities of the free-base 5,10,15,20-tetrakis(4-methoxyphenyl)porphyrin (TMP) and their metal complexes with zinc(II) (ZnTMP), copper(II) (CuTMP) and cadmium(II) (CdTMP) have been compared in two systems: reverse micelle of n-heptane/sodium bis(2-ethylhexyl)sulfosuccinate/water bearing photooxidizable substrates and Hep-2 human larynx carcinoma cell line. The quantum yields of singlet molecular oxygen, O2(1 delta g), production (phi delta) of TMP, ZnTMP and CdTMP in tetrahydrofuran, were determined yielding values of 0.65, 0.73 and 0.73, respectively, while O2(1 delta g) formation was not detected for CuTMP. In the reverse micellar system, the amino acid L-tryptophan (Trp) was used as biological substrate to analyze the O2(1 delta g)-mediated photooxidation. The observed rate constants for Trp photooxidation (kobsTrp) were proportional to the sensitizer quantum yield of O2(1 delta g). A value of approximately 2 x 10(7) s-1 M-1 was found for the second-order rate constant of Trp (krTry) in this system. The response of Hep-2 cells to cytotoxicity photoinduced by these agents in a biological medium was studied. The Hep-2 cultures were treated with 1 microM of porphyrin for 24 h at 37 degrees C and the cells exposed to visible light. The cell survival at different light exposure levels was dependent on phi delta. Under these conditions, the cytotoxic effect increases in the order: Cu-TMP < TMP < ZnTMP approximately CdTMP, correlating with the production of O2(1 delta g). A similar behavior was observed in both the chemical and biological media indicating that the O2(1 delta g) mediation appears to be mainly responsible for the cell inactivation.     

High-performance liquid-chromatographic analysis of trimethoprim and sulphamethoxazole in plasma

Summary 4 combination preparations of Trimethoprim (TMP) and Sulphamethoxazole (SMZ) were administered to 8 healthy male subjects and plasma samples were analysed after extraction of TMP and SMZ by high-performance liquid chromatography with a variable UV-detector at 230 and 280 nm. The Chromatographic system consisted of a Waters reversed-phase C₁₈ column and a mobile phase containing phosphate buffer, pH 5.0, and ethanol (80 + 20). A dose of 80 mg TMP × 400 mg SMZ results in a plasma concentration of 0.05–1.0 g/ml TMP and 1–20 g/ml SMZ during 26 h after drug administration. The relative standard deviation for TMP was found to be ±5–7% and for SMZ ±2–3%.

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HPLC-Analyse von Trimethoprim und Sulfamethoxazol in Plasma

Zusammenfassung 4 Kombinationspräparate von Trimethoprim (TMP) und Sulphamethoxazol (SMZ) wurden 8 gesunden männlichen Probanden verabreicht. Die Bestimmung von TMP und SMZ in Plasmaproben erfolgte nach Extraktion durch Hochdruckflüssigkeits-Chromatographie mit einem UV-Detektor bei 230 und 280 nm. Es wurden eine Waters-Reversed-Phase-C₁₈-Säule und ein Phosphatpuffer(pH 5,0)-Ethanolgemisch (80 + 20) als Fließmittel verwendet. Nach Verabreichung einer Dosis von 80 mg TMP + 400 mg SMZ betrugen während 26 h die Plasmakonzentrationen von TMP und SMZ 0,05-1 g bzw. 1–20 g/ ml. Die relative Standardabweichung für TMP beträgt ±5–7% und für SMZ ±2–3%.

     

Kinetics and Mechanism of 2,3,6-Trimethylphenol Oxidation by Hydrogen Peroxide in the Presence of TiO2–SiO2 Aerogel

The product and kinetics studies of 2,3,6-trimethylphenol (TMP) oxidation by 30% aqueous ₂₂ in the presence of a heterogeneous catalyst, TiO₂–SiO₂ aerogel, are performed in an MeCN medium. The main reaction products are 2,3,5-trimethyl-1,4-benzoquinone and 2,2",3,3",6,6"-hexamethyl-4,4"-biphenol. The reaction is first-order in ₂₂ and fractional order (1–0) in TMP. The reaction rate is proportional to the catalyst amount and depends on the water concentration in the reaction mixture in a complex manner. The results suggest the formation of an active intermediate on the titanium center. In this intermediate containing both a TMP molecule and the hydroperoxide group, inner-sphere one-electron oxidation of TMP occurs to give the phenoxyl radical.     

Oxygen-supplied mesoporous carbon nanoparticles for enhanced photothermal/photodynamic synergetic therapy against antibiotic-resistant bacterial infections

Pandemic and epidemic spread of antibiotic-resistant bacterial infections would result in a huge number of fatalities globally. To combat antibiotic-resistant pathogens, new antimicrobial strategies should be explored and developed to confront bacteria without acquiring or increasing drug-resistance. Here, oxygen saturated perfluorohexane (PFH)-loaded mesoporous carbon nanoparticles (CIL@ICG/PFH@O₂) with photothermal therapy (PTT) and enhanced photodynamic therapy (PDT) utility are developed for antibacterial applications. Ionic liquid groups are grafted onto the surface of mesoporous carbon nanoparticles, followed by anion-exchange with the anionic photosensitizer indocyanine green (ICG) and loading oxygen saturated PFH to prepare CIL@ICG/PFH@O₂. These CIL@ICG/PFH@O₂ nanoparticles exhibit effective PTT and enhanced PDT properties simultaneously upon 808 nm light irradiation. In vitro assays demonstrate that CIL@ICG/PFH@O₂ shows a synergistic antibacterial action against antibiotic-resistant pathogens (methicillin-resistant Staphylococcus aureus and kanamycin-resistant Escherichia coli). Moreover, CIL@ICG/PFH@O₂ could effectively kill drug-resistant bacteria in vivo to relieve inflammation and eliminate methicillin-resistant Staphylococcus aureus-wound infection under NIR irradiation, and the released oxygen can increase collagen deposition, epithelial tissue formation and blood vessel formation to promote wound healing while enhancing the PDT effect. This study proposes a platform with enhanced PTT/PDT effects for effective, controlled, and precise treatment of topical drug-resistant bacterial infections.

We report oxygen saturated perfluorohexane (PFH)-loaded mesoporous carbon nanoparticles (CIL@ICG/PFH@O₂) with photothermal therapy (PTT) and enhanced photodynamic therapy (PDT) utility for antibacterial applications.     

Type I macrophage activator photosensitizer against hypoxic tumors

Photodynamic immunotherapy has emerged as a promising strategy to treat cancer. However, the hypoxic nature of most solid tumors and notoriously immunosuppressive tumor microenvironment could greatly compromise the efficacy of photodynamic immunotherapy. To address this challenge, we rationally synthesized a type I photosensitizer of TPA-DCR nanoparticles (NPs) with aggregation-enhanced reactive oxygen species generation via an oxygen-independent pathway. We demonstrated that the free radicals produced by TPA-DCR NPs could reprogram M0 and M2 macrophages into an anti-tumor state, which is not restricted by the hypoxic conditions. The activated M1 macrophages could further induce the immunogenic cell death of cancer cells by secreting pro-inflammatory cytokines and phagocytosis. In addition, in vivo anti-tumor experiments revealed that the TPA-DCR NPs could further trigger tumor immune response by re-educating tumor-associated macrophages toward M1 phenotype and promoting T cell infiltration. Overall, this work demonstrates the design of type I organic photosensitizers and mechanistic investigation of their superior anti-tumor efficacy. The results will benefit the exploration of advanced strategies to regulate the tumor microenvironment for effective photodynamic immunotherapy against hypoxic tumors.

The photosensitizer-triggered macrophage-mediated photodynamic immunotherapy is reported. The TPA-DCR NPs induce the ICD of hypoxic tumor by generating type I ROS to polarize macrophage, then promote tumor infiltration of T cells.     

Delivery of Methylene Blue and meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate from cross-linked poly(vinyl alcohol) hydrogels: A potential means of photodynamic therapy of infected wounds

Poly(vinyl alcohol)–borate complexes were evaluated as a potentially novel drug delivery platform suitable for in vivo use in photodynamic antimicrobial chemotherapy (PACT) of wound infections. An optimised formulation (8.0% w/w PVA, 2.0% w/w borax) was loaded with 1.0 mg ml⁻¹ of the photosensitisers Methylene Blue (MB) and meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate (TMP). Both drugs were released to yield receiver compartment concentrations (>5.0 μg ml⁻¹) found to be phototoxic to both planktonic and biofilm-grown methicillin-resistant Staphylococcus aureus (MRSA), a common cause of wound infections in hospitals. Newborn calf serum, used to simulate the conditions prevalent in an exuding wound, did not adversely affect the properties of the hydrogels and had no significant effect on the rate of TMP-mediated photodynamic kill of MRSA, despite appreciably reducing the fluence rate of incident light. However, MB-mediated photodynamic kill of MRSA was significantly reduced in the presence of calf serum and when the clinical isolate was grown in a biofilm. Results support the contention that delivery of MB or TMP using gel-type vehicles as part of PACT could make a contribution to the photodynamic eradication of MRSA from infected wounds.     

Microwave assisted synthesis of dihydropyrrole by AgOAc catalyzed intramolecular cyclization reaction of homopropargyl amine

A series of 5-aryl dihydropyrrole was synthesized from the intramolecular cyclization reaction of homopropargyl amine in the presence of AgOAc as catalyst under microwave irradiation reaction conditions. The homopropargyl amine was prepared by the reaction of propargyl bromide with N-tosyl aldimine under a sonochemical Barbier-type reaction condition. Further aromatization reaction of 5-aryl dihydropyrrole in KOtBu/DMSO can afford 2-aryl pyrrole under microwave irradiation reaction conditions.     

A light-controlled multi-step drug release nanosystem targeting tumor hypoxia for synergistic cancer therapy

Hypoxia is a major obstacle for cancer therapy due to its association with cell proliferation, tumor distant metastasis, and treatment resistance. In this study, a hypoxia-activated bifunctional prodrug (CC5) was designed, synthesized and encapsulated by a photo-responsive ruthenium complex-derived polymer to yield a light-controlled multi-step drug release system (CC5-RuCa) for synergistic therapy against tumor hypoxia. Under NIR irradiation, CC5-RuCa not only generated ROS to kill the cancer cells in the exterior of the tumor but also released the prodrug CC5 with enhanced intratumoral penetration in the severe hypoxia region inside the tumor tissue. In vivo studies on MDA-MB-231 xenograft models revealed that CC5-RuCa with preferential accumulation in the tumor exhibited highly efficient tumor regression through the synergistic effect of photodynamic therapy and hypoxia-activated chemotherapy.

A photo-responsive ruthenium complex-derived micelle (CC5-RuCa) loaded with CC5 was prepared for light and tumor microenvironment-controlled multistage drug-release.     

CO/light dual-activatable Ru(ii)-conjugated oligomer agent for lysosome-targeted multimodal cancer therapeutics

Stimuli-activatable and subcellular organelle-targeted agents with multimodal therapeutics are urgently desired for highly precise and effective cancer treatment. Herein, a CO/light dual-activatable Ru(ii)-oligo-(thiophene ethynylene) (Ru-OTE) for lysosome-targeted cancer therapy is reported. Ru-OTE is prepared via the coordination-driven self-assembly of a cationic conjugated oligomer (OTE-BN) ligand and a Ru(ii) center. Upon the dual-triggering of internal gaseous signaling molecular CO and external light, Ru-OTE undergoes ligand substitution and releases OTE-BN followed by dramatic fluorescence recovery, which could be used for monitoring drug delivery and imaging guided anticancer treatments. The released OTE-BN selectively accumulates in lysosomes, physically breaking their integrity. Then, the generated cytotoxic singlet oxygen (¹O₂) causes severe lysosome damage, thus leading to cancer cell death via photodynamic therapy (PDT). Meanwhile, the release of the Ru(ii) core also suppresses cancer cell growth as an anticancer metal drug. Its significant anticancer effect is realized via the multimodal therapeutics of physical disruption/PDT/chemotherapy. Importantly, Ru-OTE can be directly photo-activated using a two-photon laser (800 nm) for efficient drug release and near-infrared PDT. Furthermore, Ru-OTE with light irradiation inhibits tumor growth in an MDA-MB-231 breast tumor model with negligible side effects. This study demonstrates that the development of an activatable Ru(ii)-conjugated oligomer potential drug provides a new strategy for effective subcellular organelle-targeted multimodal cancer therapeutics.

The anticancer therapeutics of lysosome disruption/PDT/chemotherapy based on Ru-OTE complex was achieved, which provides a new strategy for developing multimodal and effective stimuli-activatable subcellular organelle-targeted cancer therapeutics.     

Ruthenium Dioxide Electrodes as Suitable Anodes for Water Photolysis

This paper presents a cell system in which a photoinduced redox reaction occurs in the cathodic compartment which is coupled to a RuO₂-anode. The light induced oxidation of the ruthenium complex Ru (bipy) by peroxodisulfate is used to illustrate that even under diffuse room light irradiation the photopotentials developed at the Pt-cathode are sufficient to afford water oxidation in the anode compartment. The oxygen produced at the RuO₂-electrode stands in a stochiometric relation to the current passed through the circuit. Implications for a cell system in which H₂ and O₂ are produced in separate compartments under illumination are discussed.     

Assessing the In Vitro Activity of Selected Porphyrins in Human Colorectal Cancer Cells

Standard in vitro analyses determining the activity of different compounds included in the chemotherapy of colon cancer are currently insufficient. New ideas, such as photodynamic therapy (PDT), may bring tangible benefits. The aim of this study was to show that the biological activity of selected free-base and manganese (III) metallated porphyrins differs in the limitation of colon cancer cell growth in vitro. White light irradiation was also hypothesized to initiate a photodynamic effect on tested porphyrins. Manganese porphyrin (>1 μM) significantly decreased the viability of the colon tumor and normal colon epithelial cells, both in light/lack of light conditions, while decreasing a free-base porphyrin after only 3 min of white light irradiation. Both porphyrins interacted with cytostatics in an antagonistic manner. The manganese porphyrin mainly induced apoptosis and necrosis in the tumor, and apoptosis in the normal cells, regardless of light exposure conditions. The free-base porphyrin conducted mainly apoptosis and autophagy. Normal and tumor cells released low levels of IL-1β and IL-10. Tumor cells released a low level of IL-6. Light conditions and porphyrins were influenced at the cytokine level. Tested manganese (III) metallated and free-base porphyrins differ in their activity against human colon cancer cells. The first showed no photodynamic, but a toxic activity, whereas the second expressed high photodynamic action. White light use may induce a photodynamic effect associated with porphyrins.     

Degradation efficiencies and mechanisms of the ZnO-mediated photocatalytic degradation of Basic Blue 11 under visible light irradiation

A ZnO-mediated photocatalysis process was used to successfully degrade Basic Blue 11 (BB-11) under visible light irradiation. The effects of influential factors like initial dye concentration, catalyst dosage, and initial pH were studied. To obtain a better understanding the mechanistic details of ZnO-assisted photodegradation of the BB-11 dye with low watt visible light irradiation, a large number of the intermediates resulting from the photodegradation were separated, identified, and characterized by high-performance liquid chromatography–photodiode array-mass spectrometry (HPLC–PDA-MS) techniques. The results indicated that the N-de-alkylation and oxidative degradation of BB-11 dye took place and that N-hydroxyalkylated intermediates were generated during the process. From the same identified intermediates we got under UV or visible light irradiation, it is proposed that the major oxidant under visible light irradiation was OH radical, not O₂⁻. HPLC–PDA-MS analysis verified the identity of intermediates, and a reaction mechanism based on them was proposed.     

Efficient and Convenient Deprotection of Thiocarbonyl to Carbonyl Compounds Using 3-Carboxypyridinium and 2,2′-Bipyridinium Chlorochromates in Solution,Dry Media,and under Microwave Irradiation

Summary. A synthetic utility of 3-carboxypyridinium (CPCC) and 2,2-bipyridinium (BPCC) chlorochromates in deprotection reactions is reported. Different types of thioamides, thioureas, thiono esters, and thioketones are deprotected to their corresponding carbonyl compounds with these reagents in good to excellent yields. The reactions were carried out in solution, under solvent-free conditions, and under microwave irradiation. The results show that with both reagents the rates of the reactions and the yields are usually highest under microwave irradiation.     

The Synthesis and Reactivity of New μ 2- and μ 3-Aminophosphinidene Cobalt Complexes

The reaction of K[Co(CO)₄] and PCl₂(TMP) at –5°C leads to the unstable and reactive -phosphinidene complex [Co₂(CO)₆{-P(TMP)}] (1), while the same reaction carried out at 35°C gives the chlorophosphido and phosphinidene bridged cluster [Co₃(CO)₇{-P(Cl)TMP}{ ₃-P(TMP)}] (2) (TMP=2,2,6,6-tetramethylpiperidyl). Compound 1 reacts with dppm (dppm=bis(diphenyl- phosphino)methane) and [Co₂(CO)₈] to form the more stable substitution product [Co₂(CO)₄{-P(TMP)}(-dppm)] (3) and [Co₄(CO)₇(-CO)₃{ ₃-P(TMP)}] (4) respectively. The first example of a cationic ₃-phosphinidene cluster compound [Co₃(CO)₉{ ₃-P(TMP)}][AlCl₄] (5) is obtained from reaction of 3 with AlCl₃. The X-ray structures of clusters 2 and 5 are discussed.     

A plasmon-enhanced theranostic nanoplatform for synergistic chemo-phototherapy of hypoxic tumors in the NIR-II window

Development of simple and effective synergistic therapy by combination of different therapeutic modalities within one single nanostructure is of great importance for cancer treatment. In this study, by integrating the anticancer drug DOX and plasmonic bimetal heterostructures into zeolitic imidazolate framework-8 (ZIF-8), a stimuli-responsive multifunctional nanoplatform, DOX-Pt-tipped Au@ZIF-8, has been successfully fabricated. Pt nanocrystals with catalase-like activity were selectively grown on the ends of the Au nanorods to form Pt-tipped Au NR heterostructures. Under single 1064 nm laser irradiation, compared with Au NRs and Pt-covered Au NRs, the Pt-tipped Au nanorods exhibit outstanding photothermal and photodynamic properties owing to more efficient plasmon-induced electron–hole separation. The heat generated by laser irradiation can enhance the catalytic activity of Pt and improve the O₂ level to relieve tumor hypoxia. Meanwhile, the strong absorption in the NIR-II region and high-Z elements (Au, Pt) of the DOX-Pt-tipped Au@ZIF-8 provide the possibility for photothermal (PT) and computed tomography (CT) imaging. Both in vitro and in vivo experimental results illustrated that the DOX-Pt-tipped Au@ZIF-8 exhibits remarkably synergistic plasmon-enhanced chemo-phototherapy (PTT/PDT) and successfully inhibited tumor growth. Taken together, this work contributes to designing a rational theranostic nanoplatform for PT/CT imaging-guided synergistic chemo-phototherapy under single laser activation.

A plasmon-enhanced theranostic nanoplatform for synergistic chemo-phototherapy (PTT/PDT) of hypoxic tumors in the NIR-II window.