Mechanoluminescence offers unique advantages over traditional photoluminescence, including deeper tissue penetration and minimal autofluorescence. However, mechanoluminescent materials typically lack the sensitivity and reusability of their biological counterparts. Inspired by the mechanoregulation of luciferase in dinoflagellate scintillons, we develop a scintillon-mimetic mechanoluminescent nanoreactor (sMLN) by integrating mechanoresponsive ferrocene (Fc) moieties into a flexible organic silica vesicle. Under ultrasound (US) irradiation, acoustic shear forces stretch and twist the Fc moiety, increasing the Fe center electron density and reducing steric hindrance, thereby facilitating substrate binding and activating a Fenton-like reaction that triggers luminol-based luminescence. Unlike conventional mechanoluminescent materials, sMLNs exhibit repeatable and long-lasting luminescence with a half-life of approximately 5.73 min, leading to a ∼2.2 × 103-fold enhancement in intensity compared to H2O sonoluminescence. This US-induced mechanoluminescence functions as an "internal light source" to excite the chromophore for bioimaging and photodynamic therapy, overcoming the limitations of light penetration depth. This high-performance platform enables intense and ultrasensitive mechanoluminescence, providing a powerful mechanochemical tool for advanced theranostic applications.

A series of D-pi-A Type-I photosensitizers (M1-M5) featuring thiophene pi-bridges and benzo[c,d]indolium acceptors was investigated to elucidate donor strength effects on O-2(center dot-) generation. Donor strength increases from M1 to M5. Stronger donors enhance charge separation, reduce exciton binding energies, and prolong triplet-state lifetimes, promoting Type-I O-2(center dot-) production. Except M1, all T-n states exhibit hybrid charge-transfer/local-excitation character, facilitating electron transfer and spin-orbit charge-transfer intersystem crossing. Thermodynamic analysis confirms feasible O-2(center dot-) generation (Delta G < 0). M5, with the strongest donor, achieves optimal performance-long triplet lifetime (279 ns) and low exciton binding energy (3.80 eV)-highlighting its potential as a high-performance Type-I photosensitizer. Extended pi-conjugation yields high oscillator strengths (>1.500) and rapid fluorescence rates (>10(8) s(-1)), enabling near-infrared imaging. This work establishes donor-driven structure-performance relationships for dual-functional Type-I photosensitizers integrating therapy and imaging.

A series of D-π-A Type-I photosensitizers (M1-M5) featuring thiophene π-bridges and benzo[c,d]indolium acceptors was investigated to elucidate donor strength effects on O2•− generation. Donor strength increases from M1 to M5. Stronger donors enhance charge separation, reduce exciton binding energies, and prolong triplet-state lifetimes, promoting Type-I O2•− production. Except M1, all Tn states exhibit hybrid charge-transfer/local-excitation character, facilitating electron transfer and spin-orbit charge-transfer intersystem crossing. Thermodynamic analysis confirms feasible O2•− generation (ΔG < 0). M5, with the strongest donor, achieves optimal performance—long triplet lifetime (279 ns) and low exciton binding energy (3.80 eV)—highlighting its potential as a high-performance Type-I photosensitizer. Extended π-conjugation yields high oscillator strengths (>1.500) and rapid fluorescence rates (>108 s-1), enabling near-infrared imaging. This work establishes donor-driven structure-performance relationships for dual-functional Type-I photosensitizers integrating therapy and imaging.

This study is dedicated to the development of novel boron-dipyrromethene (BODIPY)-based photosensitizers, focusing on investigating the regulatory mechanism of introducing different electron-donating groups at the α-position on the photosensitizing performance of thieno-bis-BODIPY derivatives, aiming to provide a theoretical basis for cancer photodynamic therapy (PDT). Five thieno-bis-BODIPY molecules (FD1-FD5) were constructed by connecting two BODIPY units via a thiophene π-bridge and introducing various substituents at the α-position of their phenyl groups. Systematic theoretical studies revealed that unilaterally substituted molecules exhibit superior photophysical properties compared to their bilaterally substituted counterparts. The key mechanisms involve structural planarization, increased electrostatic potential difference, and the formation of hybrid LE/CT characteristics in the excited state, all of which collectively promote the intersystem crossing (ISC) process. Specifically, the pyrrole-substituted FD4 exhibits the highest ISC efficiency due to its stronger electron-donating ability and greater molecular planarity, and it is predicted to possess a stronger singlet oxygen generation capability than the methoxy-substituted FD2 while maintaining fluorescence emission. In contrast, bilateral substitution leads to structural distortion, which favors fluorescence emission, as seen in FD5 which exhibits the longest absorption wavelength. This research elucidates the key mechanisms for enhancing ISC and photosensitizing performance from the perspectives of electronic structure and excited-state characteristics, providing theoretical guidance for overcoming limitations such as insufficient tissue penetration in traditional BODIPY photosensitizers and clarifying structure-activity relationships.

Mechanoenzymes, featuring catalytic activity controlled by mechanical stimuli, play key roles in maintaining metabolic order and cellular homeostasis. However, artificial nanozymes with strict spatiotemporal regulation are still rare, limiting their effectiveness in complex biological environments. Here, we introduce a mechanically regulated nanozyme (MRNZ) by integrating mechano-responsive ferrocene (Fc) units into a flexible framework. Similar to natural enzymatic activation, acoustic shear forces cause sub-nanostructural transformations of Fc units, leading to decreased electron density and reduced steric hindrance at Fe active sites, reinforcing metabolic peroxidase (POD)-like activity. This mechanical activation enables precise modulation of metabolic reprogramming by controlled generation of low-dose hydroxyl radicals (•OH) as second messengers, improving stem cells resilience to oxidative stress for safer and more effective therapeutic interventions. Using this mechanically regulated method, we encapsulated glucose oxidase (GOx) inside hollow MRNZ to create a multienzyme regulated nanoreactor (MRNZ@GOx) that orchestrates a cascade GOx-POD reaction under ultrasound stimulation. Such a cascade reactive oxygen species generation in tumor microenvironments potentiates chemodynamic therapy combined with immune activation. Our work introduces a mechanically responsive strategy for regulating nanozyme activity, expanding the horizons of next-generation remote and smart catalytic technologies for precise disease treatments.

Two mononuclear Ir(I)-corrorin complexes, FPh-Ir and Py-Ir, featuring peripheral κ2-N,N' dipyrrin coordination, were structurally characterized and shown to efficiently photosensitize singlet oxygen under green light (ΦΔ = 0.65-0.69 in CH3CN). TD-DFT supports a near-resonant S1 → T3 intersystem-crossing pathway with appreciable spin-orbit coupling.

This study presents a hierarchical multi-parameter framework for designing hypoxia-tolerant Type I aggregation-induced emission (AIE) photosensitizers through acceptor engineering. Enhancing electron-withdrawing capacity strengthens intramolecular charge transfer (ICT) in singlet excited states (Sn), enabling a direct charge transfer-mediated intersystem crossing (ISC) pathway. Key parameters-favorable singlet-triplet gap (ΔE > 0, thermodynamic prerequisite), low reorganization energy (λ, kinetic driver), and strong spin-orbit coupling (SOC, ISC activator)-optimize ISC efficiency, an exceptionally high S1→T1 ISC rate of 2.94 × 107 s-1 for DPCMQ. This high ISC efficiency populates the T1 state, where DPCMQ benefits from optimal descriptors (lowest Eb and λT1) for efficient electron transfer. Its performance is further boosted in aggregates by restricted molecular motion and a hydration-promoted microenvironment. This design selectively promotes hydroxyl radical (•OH) generation over oxygen-dependent superoxide pathways, while low triplet energy suppresses Type II activity. The framework provides a predictive blueprint for advanced photodynamic therapy optimized for hypoxic conditions.

The development of high-performing photocatalysts with visible-light-absorbing and oxidative properties for the degradation of organic contaminants in anaerobic microenvironments remains a challenge. Herein, a Ru-complex decorated with coumarin ([Ru(phen)2Cur]Cl2) molecules was created to achieve high absorption capacities and photocatalytic activity. Taking advantage of the nanoparticulate structure, the transformation of [Ru(phen)2Cur]Cl2 molecules into Ru(II) nanostructures (RuCur NPs) not only exhibited an extensive broad visible-light absorption spectrum but also possessed enhanced intersystem crossing efficiency and improved electron transfer. Consequently, these self-assembled nanocatalysts performed efficient photodegradation toward both antibiotics and organic dyes, especially in acidic and anaerobic environments. Mechanistically, photoactivated electrons and holes on the surface of nanostructures drive the degradation of organic molecules via direct redox reactions in an oxygen-independent manner. This result proposed a fundamental insight for developing oxygen-independent nanoparticulate photocatalysts.

This study investigates the intersystem crossing (ISC) mechanism in donor-acceptor (D-A) type distyryl-BODIPY photosensitizers, including previously reported M1 (benzene donor), M2, M3 (phenothiazine donors), and newly predicted M4 (triphenylamine donor), M5-M7 (nitrogen-containing aliphatic rings with thiophene donors). Using computational chemistry, we analyzed their geometric configurations, spectral properties, spin-orbit coupling, and electron-hole orbitals. We found that S2 is a charge transfer singlet state (1CT), T2 is a locally excited triplet state (3LE), and the S2→T2 transition is the main ISC pathway in M2-M7, following the 1CT→3LE mechanism. M5-M7 show near-vertical dihedral angles between donor and acceptor in the S2 state relative to M2-M4, facilitating charge transfer. The strain energies in the nitrogen-containing rings of M5-M7 affect oxidation potentials and ISC. M5, with the highest strain energy, shows the lowest oxidation potential, smaller ΔES2-T2, highest SOC, and fastest kisc, making it the most efficient predicted singlet oxygen producer. This research clarifies the structure-performance relationships of near-infrared D-A type distyryl-BODIPY photosensitizers and provides a theoretical foundation for developing heavy-atom-free photosensitizers with tuned fluorescence quantum yield and singlet oxygen quantum yield

AbstractWe compared a range of BODIPY dimer derivatives without installing blocking groups by optimizing geometry structures and analyzing energies, frontier molecular orbitals, Chole&Cele map, electron density difference, spin‐orbit coupling (SOC) matrix and decay rate constants from excited states. The dihedral angles of the β‐β‐linked BODIPY dimer and the α‐α‐linked BODIPY dimer tend to flatten in the T1 state, which is detrimental to the occurrence of the intersystem crossing (ISC). Conversely, the dihedral angle of the meso‐β‐linked BODIPY dimer, the meso‐meso‐linked BODIPY dimer and α‐γ‐linked BODIPY dimer is within the range of 125°–143° in the T1 state, facilitating ISC and the generation of singlet oxygen. Notably, the transition from S1 to S0 involving lowest unoccupied molecular orbital to highest occupied molecular orbital with long‐wavelength emission and moderate oscillator strength underpins the remarkable long emission peaks observed experimentally for α‐γ‐linked BODIPY dimer. Moreover, the apparent SOC matrix enhances the ISC process, resulting in a respectable efficiency in generating singlet oxygen for this dimer. In meso‐β‐linked BODIPY, meso‐meso‐linked BODIPY, and α‐γ‐linked BODIPY, the S1→T1 process is characterized by a significant charge transfer, specifically transitioning from the 1CT state to the 3LE state, indicative of a spin‐orbit charge transfer ISC (SOCT‐ISC) mechanism. The ability to regulate the photosensitivity of BODIPY dimers by adjusting the dihedral angle between the two units in the T1 state unveils new avenues for designing high‐performance photosensitizers for both therapeutic and imaging applications.

The integration of photothermal therapy (PTT) and photodynamic therapy (PDT) presents a promising strategy for the treatment of hypoxic cancers. However, the conventional synergy of PTT and PDT still necessitate high-power laser irradiation, introducing damage and edema in normal tissues. Consequently, a One-for-All photo-therapy agent Oxygen (O2)@Perfluorocarbon (PF)@INF, which possesses the multifunctional capabilities of gentle photothermal effects, thermally-triggered oxygen release, and enhanced PDT, has been developed in this study for synergistic PDT/PTT under low-density light irradiation. Cyanine dyes INF perform PTT within an alkaline environment, exhibiting high root-mean-square displacement (RMSD) (S0-T1) values (0.4268 angstrom), whereas PDT occurs in acidic compartments, displaying significantly larger spin-orbit coupling (SOC) (S1-T1) values (102.00 cm-1). This bidirectional pH-sensitive functionality (pKa = 7.83) is achieved by incorporating photoinduced intramolecular electron transfer (PIET) and heavy atom effects into the INF structure. These characteristics combine the ability of INF to target both lysosomes and mitochondria (R2 = 0.92), potentially synergizing PDT and PTT in tumors. Additionally, the amphiphilic nature of INF facilitates the encapsulation of oxygen-carrying PF via intermolecular forces, enabling the preparation of O2@PF@INF (165.86 nm). Under low-density light irradiation (180 mW/cm2), the photothermal effect can enhance oxygen release from O2@PF@INF via a cascading reaction, thereby improving the efficacy of PDT and compensating for the diminished efficiency of PTT due to the lack of high-density irradiation. This research highlights a promising advancement in phototherapy and proposes an innovative method for designing multifunctional nano-phototherapy agents tailored specifically for the treatment of hypoxic tumors.

Improving the photosensitization efficiency represents a critical challenge in photodynamic therapy (PDT) research. While cyanines exhibit potential as photosensitizers (PSs) due to their large extinction coefficients and excellent biocompatibility, the inherent limitations in intersystem crossing severely affect therapeutic efficacy. Herein, we proposed a bottom-up magnetically enhanced photodynamic therapy (magneto-PDT) paradigm employing fluorobenzene-substituted pentamethine cyanine as type-I reactive oxygen species generators. Based on the radical pair mechanism and magnetic field effect, the notable difference in g-factors (Δg) between PSs and oxyradicals enabled magnetically responsive amplification of Cy5-3,4,5-3F-mediated hydroxyl radical (•OH) and superoxide anion radical (O2•-) production, achieving maximum yield enhancements of 66.9 and 28.0% respectively at 500 mT. This magnetically augmented oxyradicals generation exhibited universal cytotoxicity superiority over conventional PDT protocols in various cancer cell models. Notably, the semi-inhibitory concentration (IC50) of murine mammary carcinoma 4T1 cells demonstrated a remarkable reduction under both normoxic and hypoxic conditions, with the most pronounced decrease observed in normoxia from 0.91 μM (PDT alone) to 0.38 μM (magneto-PDT). The significantly magneto-enhanced therapeutic performance effectively inhibited orthotopic tumor growth. This magneto-PDT paradigm established a novel strategy for manipulating spin-dependent photosensitization processes in biological applications.

Near-infrared photosensitizers are valuable tools to improve treatment depth in photodynamic therapy (PDT). However, their low singlet oxygen ( 1 O 2 ) generation ability, indicated by low 1 O 2 quantum yield, presents a formidable challenge for PDT. To overcome this challenge, the heptamethine cyanine was decorated with biocompatible S ( Scy7 ) and Se ( Secy7 ) atom. We observe that Secy7 exhibits a redshift in the main absorption to ~840 nm and an ultra-efficient 1 O 2 generation capacity. The emergence of a strong intramolecular charge transfer effect between the Se atom and polymethine chain considerably narrows the energy gap (0.51 eV), and the heavy atom effect of Se strengthens spin–orbit coupling (1.44 cm −1 ), both of which greatly improved the high triplet state yield (61 %), a state that determines the energy transfer to O 2 . Therefore, Secy7 demonstrated excellent 1 O 2 generation capacity, which is ~24.5-fold that of indocyanine green, ~8.2-fold that of IR780, and ~1.3-fold that of methylene blue under low-power-density 850 nm irradiation (5 mW cm −2 ). Secy7 exhibits considerable phototoxicity toward cancer cells buried under 12 mm of tissue. Nanoparticles formed by encapsulating Secy7 within amphiphilic polymers and lecithin, demonstrated promising antitumor and anti-pulmonary metastatic effects, exhibiting remarkable potential for advancing PDT in deep tissues.

As a class of photosensitizers (PSs) with dual functions of photodynamic therapy (PDT) and fluorescence imaging, the relationship between the structure and dual-function of thiophene-fused-type BODIPY dyes has not been studied in depth before. We found that the thiophene-fused-type BODIPY triplet photosensitizer is produced according to the energy level matching rule and the introduction of the thiophene ring significantly reduces the energy gap Delta E-ST between singlet and triplet states, as revealed by our investigation of the excited state structures and energies of thieno-fused BODIPY dyes. At the same time, a tiny Delta E-ST also results in a greatly enhanced intersystem crossing (ISC) rate, k(ISC). The k(ISC) value of MeO-BODIPY, having the highest singlet oxygen quantum yield (Phi(Delta)), is the largest. Substitution with a strong electron donor N,N-dimethylaminophenyl (DMA) leads to the vertical configuration in the T-1 state. The small Delta E (0.0029 eV) between the HOMO and HOMO-1 triggers the photo induced electron transfer (PET) of inhibiting ISC and fluorescence. When thieno-fused BODIPYs react with pyrrole, the increase of pi-conjugation and smaller Delta EHOMO-LUMO explain the redshift in emission wavelength of thieno-pyrrole-fused BODIPY. The more planar configuration of the S-1 state and the stronger oscillator intensity reflect a higher fluorescence quantum yield (Phi(F)). The extension of pi-conjugation can cause molecules to transition to higher-level singlet excited states (S-n states, n >= 1) after absorbing energy and reduce the energy level of the excited state, resulting in multiple channels and favoring O-1(2) production for thieno-pyrrole-fused BODIPYs with electron-withdrawing groups at the para-position of the phenyl groups. Due to Delta ES0-T1 < 0.980 eV, the substitution of electron-donating groups cannot produce O-1(2). In this work, we have revealed the mechanism of ISC and the fluorescence emission process in the thiophene-fused-type BODIPY dye, which has provided a theoretical foundation and guidance for the future design of BODIPY-based heavy-atom-free PSs for molecular applications in PDT.

A series of BODIPY dimer derivatives were selected to investigate their molecular geometric structures, the spectral properties, the molecular frontier orbitals, spin–orbit coupling (SOC) matrix between the first singlet excited state (S1 state) and the first triplet excited state (T1 state) and the decay rate constant of the S1 state. BOP-3-3-BOP showed long absorption and emission spectra, significant fluorescence quantum yields (Φf) and respectable singlet oxygen quantum yields (ΦΔ) in comparison with other BODIPY dimers BOP-2-8-BOP, BOP-8-8-BOP and BOP-2-2-BOP. The C–C bond between the two units of BOP-3-3-BOP decreased in length while the ground state (S0 state) moved to the first excited state (S1 state) by absorbing energy, which closes to conjugated double C = C bond and extends π-conjugation between the two BODIPY units. The more planar between the two BODIPY units in the first excited state facilitates emitting the red fluorescent of BOP-3-3-BOP. The smaller singlet–triplet adiabatic energy gap and larger SOC value promoted the intersystem crossing (ISC) process and produced singlet oxygen with high efficiency for BOP-3-3-BOP. Furthermore, BOP-3-3-BOP has significant kf (S1→S0) and respectable kisc (S1→T1), which is expected to be used as both therapeutic and imaging agent. Our results on effectively regulating photophysical properties, ISC rates and the molecular excited state radiation decay rates by tuning different linkage position between two BODIPY units will be useful for molecular design of BODIPY dimers for fluorescence imaging guided photodynamic therapy.

Organic dyes in the excited singlet state (S-1) decay via intersystem crossing (ISC) to the triplet state, radiative dissipation as fluorescence, or nonradiative decay for thermal deactivation. Although many studies are conducted to improve ISC and fluorescence efficiency, few have optimized S-1 decay via thermal deactivation, which is crucial for designing photothermal agents. A strategy for inhibiting radiative decay and ISC by introducing electron withdraw groups (EWGs) into the meso position of heptamethine cyanines (Cy7) is reported here, which allows S-1 energy decay via nonradiative relaxation. The decrease in the electron density of Cy7 caused by EWGs improved the photostability, which is important for biological applications because conventional cyanine dyes are easily photobleached. The EWG substitutes acted as efficient rotation groups with low-energy barriers, narrowing the energy gap between S-1 and the ground state and considerably improving the photothermal conversion efficiency (PCE). The PCE of CF(3)cy with the strongest EWG is increased up to 83%. Liposome is used as a carrier to improve the biocompatibility and tumor retention of CF(3)cy, which is combined with the toll-like receptor agonist resiquimod (R848) for synergistic photothermal immunotherapy against both primary and distant tumors and elicits a long-lasting immunological memory effect.

OBJECTIVE:To explore the potential effect of ultrasound-guided stellate ganglion block (SGB) on lung protection for patients undergoing one-lung ventilation (OLV).METHODS:A total of 123 patients undergoing elective one-lung ventilation surgery were selected as research subjects in this prospective study. These patients were randomly divided into the SGB group, control group and blank group on average. Stellate ganglion block was carried out in the SGB and control groups. Patients in the SGB group were injected with 6 ml mixture of 0.25% ropivacaine hydrochloride and 1% lidocaine hydrochloride, while those in the control group were injected with 6 mL of 0.9% saline. Punctures weren't performed for patients in the blank group. The same induction and maintenance of general anesthesia was adopted for all three groups. Hemodynamics, respiratory parameters and arterial blood gas analysis were recorded after entering the operation room (T0), pre-OLV (T1), 30 min after OLV (T2), 60 min after OLV (T3), at the end of surgery (T4), and 30 min after extubation (T5). Oxygenation index (OI), pulmonary shunt fraction (Qs/Qt) and pH value were compared at different time points. Intravenous serum was collected at T0, T3 and T5 for the detection of surfactant proteins A (SP-A), superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-6 (IL-6) and interleukin-10 (IL-10) levels, respectively. The complications related to SGB after surgery and the postoperative pulmonary complications within 72 h were recorded.RESULTS:At T1, T2, and T3, MAP level in SGB group was lower than that in blank and control groups (P<0.05). At T2, and T3, SGB group had lower hear rate (HR), peak airway pressure (Ppeak) and tidal volume (TV) than blank and control groups (all P<0.05). From T2 to T5, SGB group had higher OI but lower Qs/Qt than blank and control groups (both P<0.05). At T3 and T5, SGB group had lower SP-A, IL-6, and MDA levels but higher IL-10 and SOD levels than blank and control groups (all P<0.05). There was one case of hypoxemia in the blank group within 72 h after surgery.CONCLUSION:Ultrasound-guided SGB has lung-protective effects on patients undergoing OLV, which significantly improves patients' OI, reduces intrapulmonary shunts, declines ventilator-induced lung damage, and inhibits inflammatory response as well as oxidative stress (China Clinical Trial Registry, registration number ChiCTR2000033385, https://www.chictr.org.cn).

Endoplasmic reticulum (ER) stress, caused by overproduction of reactive oxygen species (ROS), has been shown to be responsible for immunogenic cell death (ICD). Seeking ROS generator targeting ER is an optimal solution to efficiently induce ER stress. Despite clear indications of demand for ER-targeting photosensitizer, the alternative chemical tools remain limited. Herein, the first ER-localizable ICD photoinducer using thio-pentamethine cyanine dye (TCy5) to induce ER stress under mild near-infrared (NIR) irradiation has been developed. Within the ICD photoinducer design, polyfluorinated TCy5-Ph-3F possesses a selective tropism to ER accumulation and superior ROS generation capability in both normoxia and hypoxia conditions, which benefit from its low singlet-triplet gaps. Under NIR irradiation, cancer cells stained by TCy5-Ph-3F will lead to ER stress and induce massive emission of damage-associated molecular patterns, including calreticulin and heat-shock protein 70 exposure, high mobility group box 1 efflux, and adenosine triphosphate secretion. Dendritic cells maturation and CD8+ T cells activation in vivo also highlight the effectiveness. Therefore, the growth of abscopal tumors was substantially suppressed by the primary tumor treated with TCy5-Ph-3F and NIR irradiation. These results confer practical applicability that could provide a guideline for designing efficient ICD photoinducers, which will enable expanding organic molecular applications for cancer immunotherapy.

Photothermal therapy (PTT) as a single treatmentstill faces a challenge in completely eradicating deep tumors dueto the limited tissue penetration of light. The combination ofPTT and chemotherapy could effectively improve the therapeuticeffect. Herein, we report a prodrug-hemicyanine conjugate (Cy-azo) to achieve H-aggregation improved photothermal therapyand sequential hypoxia-activated chemotherapy. Due to theintroduction of the chemotherapeutic drug, nitrogen mustard,Cy-azo demonstrates high photothermal conversion efficiency(PCE, 39.3%) caused by the enhanced H-aggregation of theprodrug through pi-pi stacking. Moreover, the activated drug isreleased in the tumor hypoxic microenvironment, which can killcancer cells and greatly reduce the toxic side effects ofchemotherapy. In addition, Cy-azo is further encapsulated into polymer nanoparticles to stabilize the Cy-azo H-aggregatesand increase the tumor accumulation of Cy-azo through the enhanced permeability and retention effect (EPR). Interestingly,Cy-azo NPs show an enhanced PCE as 56.1% and demonstrate an excellent anticancer therapeutic effect under 808 nm lightirradiation. The combination of PTT with hypoxia-activated chemotherapy is promising for anticancer treatment and wouldguide future development of prodrugs for combined PTT and chemotherapy

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