Interstitial Optical Fiber-Mediated Multimodal Phototheranostics Based on an Aggregation-Induced NIR-II Emission Luminogen for Orthotopic Breast Cancer Treatment.

One-for-all phototheranostics based on a single molecule is recognized as a convenient approach for cancer treatment, whose efficacy relies on precise lesion localization through multimodal imaging, coupled with the efficient exertion of phototherapy. To unleash the full potential of phototheranostics, advancement in both phototheranostic agents and light delivery methods is essential. Herein, an integrated strategy combining a versatile molecule featuring aggregation-induced emission, namely tBuTTBD, with a modified optical fiber to realize comprehensive tumor diagnosis and "inside-out" irradiation in the orthotopic breast tumor, is proposed for the first time. Attributed to the intense donor-acceptor interaction, highly distorted conformation, abundant molecular rotors, and loose intermolecular packing upon aggregation, tBuTTBD can synchronously undergo second near-infrared (NIR-II) fluorescence emission, photothermal and photodynamic generation under laser irradiation, contributing to a trimodal NIR-II fluorescence-photoacoustic (PA)-photothermal imaging-guided phototherapy. The tumor treatment is further carried out following the insertion of a modified optical fiber, which is fabricated by splicing a flat-end fiber with an air-core fiber. This configuration aims to enable effective in situ phototherapy by maximizing energy utilization for therapeutic benefits. This work not only enriches the palette of NIR-II phototheranostic agents but also provides valuable insight for exploring an integrated phototheranostic protocol for practical cancer treatment.

A planar electronic acceptor motif contributing to NIR-II AIEgen with combined imaging and therapeutic applications.

Designing molecules with donor-acceptor-donor (D-A-D) architecture plays an important role in obtaining second near-infrared region (NIR-II, 1000-1700 nm) fluorescent dyes for biomedical applications; however, this always comes with a challenge due to very limited electronic acceptors. On the other hand, to endow NIR-II fluorescent dyes with combined therapeutic applications, trivial molecular design is indispensable. Herein, we propose a pyrazine-based planar electronic acceptor with a strong electron affinity, which can be used to develop NIR-II fluorescent dyes. By structurally attaching two classical triphenylamine electronic donors to it, a basic D-A-D module, namely Py-NIR, can be generated. The planarity of the electronic acceptor is crucial to induce a distinct NIR-II emission peaking at ∼1100 nm. The unique construction of the electronic acceptor can cause a twisted and flexible molecular conformation by the repulsive effect between the donors, which is essential to the aggregation-induced emission (AIE) property. The tuned intramolecular motions and twisted D-A pair brought by the electronic acceptor can lead to a remarkable photothermal conversion with an efficiency of 56.1% and induce a type I photosensitization with a favorable hydroxyl radical (OH˙) formation. Note that no additional measures are adopted in the molecular design, providing an ideal platform to realize NIR-II fluorescent probes with synergetic functions based on such an acceptor. Besides, the nanoparticles of Py-NIR can exhibit excellent NIR-II fluorescence imaging towards orthotopic 4T1 breast tumors in living mice with a high sensitivity and contrast. Combined with photothermal imaging and photoacoustic imaging caused by the thermal effect, the imaging-guided photoablation of tumors can be well performed. Our work has created a new opportunity to develop NIR-II fluorescent probes for accelerating biomedical applications.

An All-Rounder for NIR-II Phototheranostics: Well-Tailored 1064 nm-Excitable Molecule for Photothermal Combating of Orthotopic Breast Cancer.

The second near-infrared (NIR-II, 1000-1700 nm) light-activated organic photothermal agent that synchronously enables satisfying NIR-II fluorescence imaging is highly warranted yet rather challenging on the basis of the overwhelming nonradiative decay. Herein, such an agent, namely TPABT-TD, was tactfully designed and constructed via employing benzo[c]thiophene moiety as bulky electron donor/π-bridge and tailoring the peripheral molecular rotors. Benefitting from its high electron donor-acceptor strength and finely modulated intramolecular motion, TPABT-TD simultaneously exhibits ultralong absorption in NIR-II region, intense fluorescence emission in the NIR-IIa (1300-1500 nm) region as nanoaggregates, and high photothermal conversion upon 1064 nm laser irradiation. Those intrinsic advantages endow TPABT-TD nanoparticles with prominent fluorescence/photoacoustic/photothermal trimodal imaging-guided NIR-II photothermal therapy against orthotopic 4T1 breast tumor with negligible adverse effect.

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.

An NIR-II Excitable AIE Small Molecule with Multimodal Phototheranostic Features for Orthotopic Breast Cancer Treatment.

One-for-all phototheranostics, referring to a single component simultaneously exhibiting multiple optical imaging and therapeutic modalities, has attracted significant attention due to its excellent performance in cancer treatment. Benefitting from the superiority in balancing the diverse competing energy dissipation pathways, aggregation-induced emission luminogens (AIEgens) are proven to be ideal templates for constructing one-for-all multimodal phototheranostic agents. However, to this knowledge, the all-round AIEgens that can be triggered by a second near-infrared (NIR-II, 1000-1700 nm) light have not been reported. Given the deep tissue penetration and high maximum permissible exposure of the NIR-II excitation light, herein, this work reports for the first time an NIR-II laser excitable AIE small molecule (named BETT-2) with multimodal phototheranostic features by taking full use of the advantage of AIEgens in single molecule-facilitated versatility as well as synchronously maximizing the molecular donor-acceptor strength and conformational distortion. As formulated into nanoparticles (NPs), the high performance of BETT-2 NPs in NIR-II light-driven fluorescence-photoacoustic-photothermal trimodal imaging-guided photodynamic-photothermal synergistic therapy of orthotopic mouse breast tumors is fully demonstrated by the systematic in vitro and in vivo evaluations. This work offers valuable insights for developing NIR-II laser activatable one-for-all phototheranostic systems.

More Is Better: Dual-Acceptor Engineering for Constructing Second Near-Infrared Aggregation-Induced Emission Luminogens to Boost Multimodal Phototheranostics.

The manipulation of electron donor/acceptor (D/A) shows an endless impetus for innovating optical materials. Currently, there is booming development in electron donor design, while research on electron acceptor engineering has received limited attention. Inspired by the philosophical idea of "more is different", two systems with D'-D-A-D-D' (1A system) and D'-D-A-A-D-D' (2A system) structures based on acceptor engineering were designed and studied. It was demonstrated that the 1A system presented a weak aggregation-induced emission (AIE) to aggregation-caused quenching (ACQ) phenomenon, along with the increased acceptor electrophilicity and planarity. In sharp contrast, the 2A system with one more acceptor exhibited an opposite ACQ-to-AIE transformation. Interestingly, the fluorophore with a more electron-deficient A-A moiety in the 2A system displayed superior AIE activity. More importantly, all compounds in the 2A system showed significantly higher molar absorptivity (ε) in comparison to their counterparts in the 1A system. Thanks to the highest ε, near-infrared-II (NIR-II, 1000-1700 nm) emission, desirable AIE property, favorable reactive oxygen species (ROS) generation, and high photothermal conversion efficiency, a representative member of the 2A system handily performed in fluorescence-photoacoustic-photothermal multimodal imaging-guided photodynamic-photothermal collaborative therapy for efficient tumor elimination. Meanwhile, the NIR-II fluorescence imaging of blood vessels and lymph nodes in living mice was also accomplished. This study provides the first evidence that the dual-connected acceptor tactic could be a new molecular design direction for the AIE effect, resulting in high ε, aggregation-intensified NIR-II fluorescence emission, and improved ROS and heat generation capacities of phototheranostic agents.

Acceptor engineering-facilitated versatile AIEgen for mitochondria-targeted multimodal imaging-guided cancer photoimmunotherapy.

Photoimmunotherapy has been acknowledged to be an unprecedented strategy to obtain significantly improved cancer treatment efficacy. In this regard, the exploitation of high-performance multimodal phototheranostic agents is highly desired. Apart from tailoring electron donors, acceptor engineering is gradually rising as a deliberate approach in this field. Herein, we rationally designed a family of aggregation-induced emission (AIE)-active compounds with the same donors but different acceptors based on the acceptor engineering. Through finely adjusting the functional groups on electron acceptors, the electron affinity of electron acceptors and the conformation of the compounds were simultaneously modulated. It was found that one of the molecules (named DCTIC), bearing a moderately electrophilic electron acceptor and the best planarity, exhibited optimal phototheranostic properties in terms of light-harvesting ability, fluorescence emission, reactive oxygen species (ROS) production, and photothermal performance. For the purpose of amplified therapeutic outcomes, DCTIC was fabricated into tumor and mitochondria dual-targeted DCTIC nanoparticles (NPs), which afforded good performance in the fluorescence/photoacoustic/photothermal trimodal imaging-guided photodynamic/photothermal-synergized cancer immunotherapy with the combination of programmed cell death protein-1 (PD-1) antibody. Not only the primary tumors were totally eradicated, but efficient growth inhibition of distant tumors was also realized.

Type I Photosensitization with Strong Hydroxyl Radical Generation in NIR Dye Boosted by Vigorous Intramolecular Motions for Synergistic Therapy.

Development of type I photosensitizers (PSs) with strong hydroxyl radical (· OH) formation is particularly important in the anaerobic tumor treatment. On the other hand, it is challenging to obtain an efficient solid-state intramolecular motion to promote the development of molecular machine and molecular motor. However, the relationship between them is never revealed. In this work, a pyrazine-based near-infrared type I PS with remarkable donor-acceptor effect is developed. Notably, the intramolecular motions are almost maximized by the combination of intramolecular and intermolecular engineering to simultaneously introduce the unlimited bond stretching vibration and boost the group rotation. The photothermal conversion caused by the intramolecular motions is realized with efficiency as high as 86.8%. The D-A conformation of PS can also induce a very small singlet-triplet splitting of 0.07 eV, which is crucial to promote the intersystem crossing for the triplet sensitization. Interestingly, its photosensitization is closely related to the intramolecular motions, and a vigorous motion may give rise to a strong · OH generation. In view of its excellent photosensitization and photothermal behavior, the biocompatible PS exhibits a superior imaging-guided cancer synergistic therapy. This work stimulates the development of advanced PS for the biomedical application and solid-state intramolecular motions.

Synchronously Manipulating Absorption and Extinction Coefficient of Semiconducting Polymers via Precise Dual-Acceptor Engineering for NIR-II Excited Photothermal Theranostics.

Integrating the ultralong excitation wavelength, high extinction coefficient, and prominent photothermal conversion ability into a single photothermal agent is an appealing yet significantly challenging task. Herein, a precise dual-acceptor engineering strategy is exploited for this attempt based on donor-acceptor (D-A) type semiconductor polymers by subtly regulating the molar proportions of the two employed electron acceptor moieties featuring different electronic affinity and π-conjugation degrees, and making full use of the active intramolecular motion-induced photothermal effect. The optimal polymer SP4 synchronously shows desirable second near-infrared (NIR-II) absorption, an extremely high extinction coefficient, and satisfactory photothermal conversion behavior. Consequently, the unprecedented performance of SP4 NPs on 1064 nm laser-excited photoacoustic imaging (PAI)-guided photothermal therapy (PTT) is demonstrated by the precise tumor diagnosis and complete tumor elimination.

Type I Photosensitizers Based on Aggregation-Induced Emission: A Rising Star in Photodynamic Therapy.

Photodynamic therapy (PDT), emerging as a minimally invasive therapeutic modality with precise controllability and high spatiotemporal accuracy, has earned significant advancements in the field of cancer and other non-cancerous diseases treatment. Thereinto, type I PDT represents an irreplaceable and meritorious part in contributing to these delightful achievements since its distinctive hypoxia tolerance can perfectly compensate for the high oxygen-dependent type II PDT, particularly in hypoxic tissues. Regarding the diverse type I photosensitizers (PSs) that light up type I PDT, aggregation-induced emission (AIE)-active type I PSs are currently arousing great research interest owing to their distinguished AIE and aggregation-induced generation of reactive oxygen species (AIE-ROS) features. In this review, we offer a comprehensive overview of the cutting-edge advances of novel AIE-active type I PSs by delineating the photophysical and photochemical mechanisms of the type I pathway, summarizing the current molecular design strategies for promoting the type I process, and showcasing current bioapplications, in succession. Notably, the strategies to construct highly efficient type I AIE PSs were elucidated in detail from the two aspects of introducing high electron affinity groups, and enhancing intramolecular charge transfer (ICT) intensity. Lastly, we present a brief conclusion, and a discussion on the current limitations and proposed opportunities.

A cell membrane-targeting AIE photosensitizer as a necroptosis inducer for boosting cancer theranostics.

The exploration of cellular organelle-specific anchoring photosensitizers with both prominent fluorescence imaging behavior and extraordinary reactive oxygen species (ROS) production capability is highly in demand but remains a severe challenge for effective cancer theranostics involving photodynamic therapy (PDT). In this contribution, we developed a cell membrane-targeting and NIR-emission photosensitizer having an aggregation-induced emission (AIE) tendency. The AIE photosensitizer, namely TBMPEI, is capable of lighting up and ablating cancer cells by means of a necroptosis procedure enabling cell membrane rupture and DNA degradation upon light irradiation, endowing TBMPEI with impressive performance for both in vitro and in vivo fluorescence imaging-guided PDT.

Cascade C-H-Activated Polyannulations toward Ring-Fused Heteroaromatic Polymers for Intracellular pH Mapping and Cancer Cell Killing.

The development of straightforward and efficient synthetic methods toward ring-fused heteroaromatic polymers with attractive functionalities has great significance in both chemistry and materials science. Herein, we develop a facile cascade C-H-activated polyannulation route that can in situ generate multiple ring-fused aza-heteroaromatic polymers from readily available monomers in an atom-economical manner. A series of complex polybenzimidazole derivatives with high absolute molecular weights of up to 24 000 are efficiently produced in high yields within 2 h. Benefiting from their unique imidazole-containing ring-fused structures with multiple aryl pendants, the obtained polymers show excellent thermal and morphological stability, good solution processability, high refractive index, small chromic dispersion, as well as remarkable acid-base-responsive fluorescence. Taking advantage of the ratiometric fluorescence response of the triphenylamine-substituted heteroaromatic polymer to pH variations, we successfully apply it as a sensitive fluorescence probe for the mapping and quantitative analysis of intracellular pH in live cells. Furthermore, through the simple N-methylation reaction of the ring-fused polybenzimidazoles, diverse azonia-containing polyelectrolytes are readily produced, which can efficiently kill cancer cells via the synergistic effects of dark toxicity and phototoxicity.

Multimodal Imaging-Guided Photothermal Immunotherapy Based on a Versatile NIR-II Aggregation-Induced Emission Luminogen.

Synergistic photothermal immunotherapy has captured great attention owing to the mutually strengthening therapeutic outcomes towards both original tumors and abscopal tumors. Herein, a versatile theranostic agent displaying aggregation-induced emission, namely TPA-BT-DPTQ, was designed and prepared based on benzo[c]thiophene unit as a building block; it can be used for simultaneous fluorescence imaging (FLI) in the second near-infrared (NIR-II) window, photoacoustic imaging (PAI), photothermal imaging (PTI), and thermal eradication of tumors. Further experiments validate that photothermal therapy (PTT) mediated by TPA-BT-DPTQ nanoparticles not only destroys the primary tumor but also enhances immunogenicity for further suppressing the growth of tumors at distant sites. Furthermore, PTT combining a programmed death-ligand 1 (PD-L1) antibody prevents the metastasis and recurrence of cancer by potentiating the effect of immunotherapy.

The fast-growing field of photo-driven theranostics based on aggregation-induced emission.

Photo-driven theranostics, also known as phototheranostics, relying on the diverse excited-state energy conversions of theranostic agents upon photoexcitation represents a significant branch of theranostics, which ingeniously integrate diagnostic imaging and therapeutic interventions into a single formulation. The combined merits of photoexcitation and theranostics endow photo-driven theranostics with numerous superior features. The applications of aggregation-induced emission luminogens (AIEgens), a particular category of fluorophores, in the field of photo-driven theranostics have been intensively studied by virtue of their versatile advantageous merits of favorable biocompatibility, tuneable photophysical properties, unique aggregation-enhanced theranostic (AET) features, ideal AET-favored on-site activation ability and ready construction of one-for-all multimodal theranostics. This review summarised the significant achievements of photo-driven theranostics based on AIEgens, which were detailedly elaborated and classified by their diverse theranostic modalities into three groups: fluorescence imaging-guided photodynamic therapy, photoacoustic imaging-guided photothermal therapy, and multi-modality theranostics. Particularly, the tremendous advantages and individual design strategies of AIEgens in pursuit of high-performance photosensitizing output, high photothermal conversion and multimodal function capability by adjusting the excited-state energy dissipation pathways are emphasized in each section. In addition to highlighting AIEgens as promising templates for modulating energy dissipation in the application of photo-driven theranostics, current challenges and opportunities in this field are also discussed.

Aggregation-Induced Emission-Active Poly(phenyleneethynylene)s for Fluorescence and Raman Dual-Modal Imaging and Drug-Resistant Bacteria Killing.

Poly(phenyleneethynylene) (PPE) is a widely used functional conjugated polymer with applications ranging from organic optoelectronics and fluorescence sensors to optical imaging and theranostics. However, the fluorescence efficiency of PPE in aggregate states is generally not as good as their solution states, which greatly compromises their performance in fluorescence-related applications. Herein, a series of PPE derivatives with typical aggregation-induced emission (AIE) properties is designed and synthesized. In these PPEs, the diethylamino-substituted tetraphenylethene units function as the long-wavelength AIE source and the alkyl side chains serve as the functionalization site. The obtained AIE-active PPEs with large π-conjugation show strong aggregate-state fluorescence, interesting self-assembly behaviors, inherently enhanced alkyne vibrations in the Raman-silent region of cells, and efficient antibacterial activities. The PPE nanoparticles with good cellular uptake capability can clearly and sensitively visualize the tumor region and residual tumors via their fluorescence and Raman signals, respectively, to benefit the precise tumor resection surgery. After post-functionalization, the obtained PPE-based polyelectrolyte can preferentially image bacteria over mammalian cells and possesses efficient photodynamic killing capability against Gram-positive and drug-resistant bacteria. This work provides a feasible design strategy for developing functional conjugated polymers with multimodal imaging capability as well as photodynamic antimicrobial ability.

Molecular Engineering of High-Performance Aggregation-Induced Emission Photosensitizers to Boost Cancer Theranostics Mediated by Acid-Triggered Nucleus-Targeted Nanovectors.

Phototheranostics involving both fluorescence imaging and photodynamic therapy has been recognized to be potentially powerful for cancer treatment by virtue of various intrinsic advantages. However, the state-of-the-art materials in this area are still far from ideal toward practical applications, ascribed to their respective and collective drawbacks, such as inefficient imaging quality, inferior reactive oxygen species (ROS) production, the lack of subcellular-targeting capability, and dissatisfactory delivery. In this paper, these shortcomings are successfully addressed through the integration of finely engineered photosensitizers with aggregation-induced emission (AIE) features and well tailored nanocarrier systems. The yielded AIE NPs simultaneously exhibit broad absorption in the visible-light region, bright near-infrared fluorescence emission, high ROS generation, as well as tumor lysosomal acidity-activated and nucleus-targeted delivery functions, making them promising for precise and efficient phototheranostics. Both in vitro and in vivo evaluations show that the presented nanotheranostic systems bearing good photostability and appreciable biosecurity perform well in fluorescence imaging-guided photodynamic cancer therapy. This study thus not only extends the application scopes of AIE nanomaterials but also offers useful insights into constructing advanced cancer phototheranostics.

One-for-all phototheranostics: Single component AIE dots as multi-modality theranostic agent for fluorescence-photoacoustic imaging-guided synergistic cancer therapy.

Construction of single component theranostic agent with one-for-all features to concurrently afford both multi-modality imaging and therapy is an appealing yet significantly challenging task. Herein, a type of luminogens with aggregation-induced emission (AIE) characteristics are tactfully designed and facilely synthesized. These AIE luminogens (AIEgens) exhibit long emission wavelengths, good photostability, remarkable biocompatibility, good reactive oxygen species (ROS) generation performance and excellent photothermal conversion efficiency, which allow them to be powerfully utilized for in vitro and in vivo cancer phototheranostics. The results show that one of the AIEgens is capable of precisely diagnosing solid tumors of mice by means of combined near-infrared-I/II (NIR-I/II) fluorescence-photoacoustic imaging, meanwhile this AIEgen can activate photodynamic and photothermal synergistic therapy (PDT-PTT) upon laser irradiation, resulting in excellent tumor elimination efficacy with only once injection and irradiation. This study thus provides a versatile platform for practical cancer theranostics.

Good Steel Used in the Blade: Well-Tailored Type-I Photosensitizers with Aggregation-Induced Emission Characteristics for Precise Nuclear Targeting Photodynamic Therapy.

Photodynamic therapy (PDT) has long been recognized to be a promising approach for cancer treatment. However, the high oxygen dependency of conventional PDT dramatically impairs its overall therapeutic efficacy, especially in hypoxic solid tumors. Exploration of distinctive PDT strategy involving both high-performance less-oxygen-dependent photosensitizers (PSs) and prominent drug delivery system is an appealing yet significantly challenging task. Herein, a precise nuclear targeting PDT protocol based on type-I PSs with aggregation-induced emission (AIE) characteristics is fabricated for the first time. Of the two synthesized AIE PSs, TTFMN is demonstrated to exhibit superior AIE property and stronger type-I reactive oxygen species (ROS) generation efficiency owing to the introduction of tetraphenylethylene and smaller singlet-triplet energy gap, respectively. With the aid of a lysosomal acid-activated TAT-peptide-modified amphiphilic polymer poly(lactic acid)12k-poly(ethylene glycol)5k-succinic anhydride-modified TAT, the corresponding TTFMN-loaded nanoparticles accompanied with acid-triggered nuclear targeting peculiarity can quickly accumulate in the tumor site, effectively generate type-I ROS in the nuclear region and significantly suppress the tumor growth under white light irradiation with minimized systematic toxicity. This delicate "Good Steel Used in the Blade" tactic significantly maximizes the PDT efficacy and offers a conceptual while practical paradigm for optimized cancer treatment in further translational medicine.

Aggregation-Induced Emission Luminogens Married to 2D Black Phosphorus Nanosheets for Highly Efficient Multimodal Theranostics.

Inspired by the respective advantages of aggregation-induced emission (AIE)-active photosensitizers and black phosphorus nanomaterials in cancer treatment, the facile construction of novel AIE photosensitizers married to 2D black phosphorus nanosheets and their application for multimodal theranostics are demonstrated. The developed nanomaterial simultaneously possesses distinctive properties and multiple functions including excellent stability, good biocompatibility, intensive fluorescence emission in the NIR region, high-performance reactive oxygen species generation, good photothermal conversion efficiency, outstanding cellular uptake, and effective accumulation at the tumor site. Both in vitro and in vivo evaluation show that the presented nanotheranostic system is an excellent candidate for NIR fluorescence-photothermal dual imaging-guided synergistic photodynamic-photothermal therapies. This study thus not only extends the applications scope of AIE and black phosphorus materials, but also offers useful insights into designing a new generation of cancer theranostic protocol for potential clinical applications.

An All-Round Athlete on the Track of Phototheranostics: Subtly Regulating the Balance between Radiative and Nonradiative Decays for Multimodal Imaging-Guided Synergistic Therapy.

Aiming to achieve versatile phototheranostics with the integrated functionalities of multiple diagnostic imaging and synergistic therapy, the optimum use of dissipated energy through both radiative and nonradiative pathways is definitely appealing, yet a significantly challenging task. To the best of the knowledge, there have been no previous reports on a single molecular species effective at affording all phototheranostic modalities including fluorescence imaging (FLI), photoacoustic imaging (PAI), photothermal imaging (PTI), photodynamic therapy (PDT), and photothermal therapy (PTT). Herein, a simple and highly powerful one-for-all phototheranostics based on aggregation-induced emission (AIE)-active fluorophores is tactfully designed and constructed. Thanks to its strong electron donor-acceptor interaction and finely modulated intramolecular motion, the AIE fluorophore-based nanoparticles simultaneously exhibit bright near-infrared II (NIR-II) fluorescence emission, efficient reactive oxygen species generation, and high photothermal conversion efficiency upon NIR irradiation, indicating the actualization of a balance between radiative and nonradiative energy dissipations. Furthermore, the unprecedented performance on NIR-II FLI-PAI-PTI trimodal-imaging-guided PDT-PTT synergistic therapy is demonstrated by the precise tumor diagnosis and complete tumor elimination outcomes. This study thus brings a new insight into the development of superior versatile phototheranostics for practical cancer theranostics.