Gold Nanoframeworks with Mesopores for Raman–Photoacoustic Imaging and Photo‐Chemo Tumor Therapy in the Second Near‐Infrared Biowindow

Gold‐based nanostructures with tunable wavelength of localized surface plasmon resonance (LSPR) in the second near‐infrared (NIR‐II) biowindow receive increasing attention in phototheranostics. In view of limited progress on NIR‐II gold nanostructures, a particular liposome template‐guided route is explored to synthesize novel gold nanoframeworks (AuNFs) with large mesopores (≈40 nm) for multimodal imaging along with therapeutic robustness. The synthesized AuNFs exhibit strong absorbance in NIR‐II region, affording their capacity of NIR‐II photothermal therapy (PTT) and photoacoustic (PA) imaging for deep tumors. Functionalization of AuNFs with hyaluronic acid (HA) endows the targeting capacity for CD44‐overexpressed tumor cells while gatekeeping doxorubicin (DOX) loaded into mesopores. Conjugation of Raman reporter 4‐aminothiophenol (4‐ATP) onto AuNFs yields a surface‐enhanced Raman scattering (SERS) fingerprint for Raman spectroscopy/imaging. In vivo evaluation of HA‐4‐ATP‐AuNFs‐DOX on tumor‐bearing xenografts demonstrates its high efficacy in eradication of solid tumors in NIR‐II under PA–Raman dual image‐guided photo‐chemotherapy. Thus, current AuNFs offer versatile capabilities for phototheranostics.     

Tantalum Sulfide Nanosheets as a Theranostic Nanoplatform for Computed Tomography Imaging‐Guided Combinatorial Chemo‐Photothermal Therapy

Near‐infrared (NIR)‐absorbing metal‐based nanomaterials have shown tremendous potential for cancer therapy, given their facile and controllable synthesis, efficient photothermal conversion, capability of spatiotemporal‐controlled drug delivery, and intrinsic imaging function. Tantalum (Ta) is among the most biocompatible metals and arouses negligible adverse biological responses in either oxidized or reduced forms, and thus Ta‐derived nanomaterials represent promising candidates for biomedical applications. However, Ta‐based nanomaterials by themselves have not been explored for NIR‐mediated photothermal ablation therapy. In this work, an innovative Ta‐based multifunctional nanoplatform composed of biocompatible tantalum sulfide (TaS₂) nanosheets (NSs) is reported for simultaneous NIR hyperthermia, drug delivery, and computed tomography (CT) imaging. The TaS₂ NSs exhibit multiple unique features including (i) efficient NIR light‐to‐heat conversion with a high photothermal conversion efficiency of 39%, (ii) high drug loading (177% by weight), (iii) controlled drug release triggered by NIR light and moderate acidic pH, (iv) high tumor accumulation via heat‐enhanced tumor vascular permeability, (v) complete tumor ablation and negligible side effects, and (vi) comparable CT imaging contrast efficiency to the widely clinically used agent iobitridol. It is expected that this multifunctional NS platform can serve as a promising candidate for imaging‐guided cancer therapy and selection of cancer patients with high tumor accumulation.     

All‐in‐One Phototheranostics: Single Laser Triggers NIR‐II Fluorescence/Photoacoustic Imaging Guided Photothermal/Photodynamic/Chemo Combination Therapy

Development of single near‐infrared (NIR) laser triggered phototheranostics for multimodal imaging guided combination therapy is highly desirable but is still a big challenge. Herein, a novel small‐molecule dye DPP‐BT is designed and synthesized, which shows strong absorption in the first NIR window (NIR‐I) and fluorescence emission in the second NIR region (NIR‐II). Such a dye not only acts as a dual‐modal contrast agent for NIR‐II fluorescence and photoacoustic (PA) imaging, but also serves as a combined therapeutic agent for photothermal therapy (PTT) and photodynamic therapy (PDT). The single NIR laser triggered all‐in‐one phototheranostic nanoparticles are constructed by encapsulating the dye DPP‐BT, chemotherapy drug DOX, and natural phase‐change materials with a folic acid functionalized amphiphile. Notably, under NIR laser irradiation, DOX can effectively release from such nanoparticles via NIR‐induced hyperthermia of DPP‐BT. By intravenous injection of such nanoparticles into Hela tumor‐bearing mice, the tumor size and location can be accurately observed via NIR‐II fluorescence/PA dual‐modal imaging. From in vitro and in vivo therapy results, such nanoparticles simultaneously present remarkable antitumor efficacy by PTT/PDT/chemo combination therapy, which is triggered by a single NIR laser. Overall, this work provides an innovative strategy to design and construct all‐in‐one nanoplatforms for clinical phototheranostics.     

Safe‐by‐Design Exfoliation of Niobium Diselenide Atomic Crystals as a Theory‐Oriented 2D Nanoagent from Anti‐Inflammation to Antitumor

The accompanying relationship between tumor and inflammation raises the concept of concurrent antitumor and anti‐inflammation treatment in the clinic. Despite the wide application of 2D atomic crystals for cancer theranostics, their anti‐inflammation function has been rarely explored. Herein, it is reported that niobium diselenide nanosheets (NbSe₂ NSs), a “star” 2D superconducting atomic crystal, can serve as a theory‐oriented 2D nanoagent from anti‐inflammation to antitumor. A safe‐by‐design exfoliation strategy, integration of cryo‐pretreatment and DNA‐assisted exfoliation, is proposed for high‐efficiency exfoliation of atomically thin NbSe₂ NSs. Especially, computational simulation reveals that NbSe₂ NSs effectively eliminate reactive oxygen and nitrogen species (RONS) via hydrogen atom transfer and redox reaction. Upon the injection of NbSe₂ NSs into BALB/c mice, not only U87 subcutaneous tumors are rapidly ablated after photoacoustic imaging‐guided precise localization of tumor contour, but also lipopolysaccharide‐induced rear thigh inflammation or photothermal therapy‐mediated inflammation is efficiently inhibited through RONS scavenging. In addition, NbSe₂ NSs are highly biocompatible both in vitro and in vivo due to high‐security element constituent and DNA modification. The work extends the biomedical application of 2D atomic crystals for anti‐inflammatory treatment.     

Multifunctional Carbon–Silica Nanocapsules with Gold Core for Synergistic Photothermal and Chemo‐Cancer Therapy under the Guidance of Bimodal Imaging

Carbon‐based nanomaterials have been developed for photothermal cancer therapy, but it is still a great challenge to fabricate their multifunctional counterparts with facile methods, good biocompatibility and dispersity, and high efficiency for cancer theranostics. In this work, an alternative multifunctional nanoplatform is developed based on carbon–silica nanocapsules with gold nanoparticle in the cavity (Au@CSN) for cancer theranostics. The encapsulated chemodrug doxorubicin can be released from the Au@CSN with mesoporous and hollow structure in a near‐infrared light and pH stimuli‐responsive manner, facilitating spatiotemporal therapy to decrease off‐target toxicity. The nanocapsules with efficient photothermal conversion and excellent biocompatibility achieve a synergistic effect of photothermal and chemotherapy. Furthermore, the nanocapsules can act as a multimodal imaging agent of computed tomography and photoacoustic tomography imaging for guiding the therapy. This new design platform can provide a promising strategy for precise cancer theranostics.     

Copper(I) Phosphide Nanocrystals for In Situ Self‐Generation Magnetic Resonance Imaging‐Guided Photothermal‐Enhanced Chemodynamic Synergetic Therapy Resisting Deep‐Seated Tumor

Fe‐based Fenton agents can generate highly reactive and toxic hydroxyl radicals (·OH) in the tumor microenvironment (TME) for chemodynamic therapy (CDT) with high specificity. However, the strict condition (lower pH environment: 3–4) of the highly efficient Fenton reaction limits its practical application in the clinic. Development of new CDT agents more suitable for TME is significant and challenging. A highly efficient Cu(I)‐based CDT agent, copper(I) phosphide nanocrystals (CP NCs), which is more adaptable to the pH value of TME than Fe‐based agents, thereby producing more ·OH to trigger the apoptosis of cancer cells, is prepared. Moreover, the excess glutathione (GSH) in TME can reduce the Cu(II) produced by a Fenton‐like reaction to Cu(I), further increasing the generation rate of ·OH and relieving tumor antioxidant ability. Furthermore, owing to their strong absorption in the NIR II region, CP NCs exhibit an excellent photothermal conversion effect, which can further improve the Fenton reaction. What is more, CP NCs can act as in situ self‐generation magnetic resonance imaging (MRI) agents owing to the generation of paramagnetic Cu(II) in response to excess H₂O₂ in the TME. These properties may open up the exploration of copper‐based materials in clinical application of self‐generation imaging‐guided synergetic treatment.     

Photoactive Hybrid AuNR‐Pt@Ag2S Core–Satellite Nanostructures for Near‐Infrared Quantitive Cell Imaging

The quantitative detection of microRNA (miR) and multimode‐imaging‐induced photothermal therapy in vivo have become the focus of much attention. Platinum (Pt) decorated gold nanorods (AuNR‐Pt) and Ag₂S core–satellite (AuNR‐Pt@Ag₂S) multifunctional nanostructures are fabricated to quantify intracellular miRs (miR‐21), near‐infrared fluorescence cell quantitative imaging, and tumor ablation in vivo. When combined with miR‐21, the nanoassembly displays significant fluorescence intensity in the second window of the near‐infrared region (1000–1700 nm) after 808 nm excitation. The Ag₂S fluorescence intensity has a good linear relationship with the amount of intracellular miR in the range of 0.054–20.45 amol ng_RNA ^?1 and a limit of detection of 0.0082 amol ng_RNA ^?1. The nanoassembly is also used to develop multimodal bioimaging, including near‐infrared, X‐ray computed tomographic, and photoacoustic imaging in HeLa‐tumor‐bearing mice. Moreover, the tumors are completely eliminated by the high photothermal capacity of the AuNR‐Pt@Ag₂S assembly. This nanoassembly provides a multifunctional nanoplatform for the ultrasensitive detection of miRs and tumor diagnosis and therapy in vivo.     

Ultrathin Molybdenum Carbide MXene with Fast Biodegradability for Highly Efficient Theory‐Oriented Photonic Tumor Hyperthermia

The explosion of emerging high‐performance 2D MXenes in theranostic nanomedicine is still at the preliminary stage. Despite tremendous efforts devoted to photonic tumor hyperthermia, current photothermal‐conversion nanoagents still suffer from critical issues preventing further clinical translation such as low biodegradability. Here, for the first time, the construction of novel 2D molybdenum carbide (Mo₂C) MXenes for photonic tumor hyperthermia is reported. The structure of both bulk Mo₂Ga₂C ceramic and Mo₂C MXene is fully revealed. Especially, computational simulation, as a novel strategy and a powerful tool for photonic‐performance prediction, is employed to reveal that Mo₂C MXene is featured with intense near‐infrared (NIR) absorption, covering the first and the second biological transparency window (NIR I and II). After further surface engineering with polyvinyl alcohol (PVA), Mo₂C‐PVA nanoflakes exhibit high biocompatibility and fast degradability. Importantly, it is experimentally corroborated that Mo₂C‐PVA nanoflakes possess intriguing broad absorption band spanning NIR in both the I and II regions, and desirable photothermal‐conversion efficiency (24.5% for NIR I and 43.3% for NIR II). This study not only broadens the nanomedical applications of MXene by fabricating novel material members (Mo₂C), but also provides the paradigm of inorganic multifunctional biomedical nanoplatform with desirable biodegradability and high therapeutic performance.     

A New Single 808 nm NIR Light‐Induced Imaging‐Guided Multifunctional Cancer Therapy Platform

The NIR light‐induced imaging‐guided cancer therapy is a promising route in the targeting cancer therapy field. However, up to now, the existing single‐modality light‐induced imaging effects are not enough to meet the higher diagnosis requirement. Thus, the multifunctional cancer therapy platform with multimode light‐induced imaging effects is highly desirable. In this work, captopril stabilized‐Au nanoclusters Au₂₅(Capt)₁₈?(Au₂₅) are assembled into the mesoporous silica shell coating outside of Nd³⁺‐sensitized upconversion nanoparticles (UCNPs) for the first time. The newly formed Au₂₅ shell exhibits considerable photothermal effects, bringing about the photothermal imaging and photoacoustic imaging properties, which couple with the upconversion luminescence imaging. More importantly, the three light‐induced imaging effects can be simultaneously achieved by exciting with a single NIR light (808 nm), which is also the triggering factor for the photothermal and photodynamic cancer therapy. Besides, the nanoparticles can also present the magnetic resonance and computer tomography imaging effects due to the Gd³⁺ and Yb³⁺ ions in the UCNPs. Furthermore, due to the photodynamic and the photothermal effects, the nanoparticles possess efficient in vivo tumor growth inhibition under the single irradiation of 808 nm light. The multifunctional cancer therapy platform with multimode imaging effects realizes a true sense of light‐induced imaging‐guided cancer therapy.     

Design and Synthesis of “All‐in‐One” Multifunctional FeS2 Nanoparticles for Magnetic Resonance and Near‐Infrared Imaging Guided Photothermal Therapy of Tumors

The ideal theranostic nanoplatform for tumors is a single nanoparticle that has a single semiconductor or metal component and contains all multimodel imaging and therapy abilities. The design and preparation of such a nanoparticle remains a serious challenge. Here, with FeS₂ as a model of a semiconductor, the tuning of vacancy concentrations for obtaining “all‐in‐one” type FeS₂ nanoparticles is reported. FeS₂ nanoparticles with size of ≈30 nm have decreased photoabsorption intensity from the visible to near‐infrared (NIR) region, due to a low S vacancy concentration. By tuning their shape/size and then enhancing the S vacancy concentration, the photoabsorption intensity of FeS₂ nanoparticles with size of ≈350 nm (FeS₂‐350) goes up with the increase of the wavelength from 550 to 950 nm, conferring the high NIR photothermal effect for thermal imaging. Furthermore, this nanoparticle has excellent magnetic properties for T₂‐weighted magnetic resonance imaging (MRI). Subsequently, FeS₂‐350 phosphate buffer saline (PBS) dispersion is injected into the tumor‐bearing mice. Under the irradiation of 915‐nm laser, the tumor can be ablated and the metastasis lesions in liver suffer significant inhibition. Therefore, FeS₂‐350 has great potential to be used as novel “all‐in‐one” multifunctional theranostic nanoagents for MRI and NIR dual‐modal imaging guided NIR‐photothermal ablation therapy (PAT) of tumors.     

Ultra‐Small Iron Oxide Doped Polypyrrole Nanoparticles for In Vivo Multimodal Imaging Guided Photothermal Therapy

Recently, near‐infrared (NIR) absorbing conjugated polymeric nanoparticles have received significant attention in photothermal therapy of cancer. Herein, polypyrrole (PPy), a NIR‐absorbing conjugate polymer, is used to coat ultra‐small iron oxide nanoparticles (IONPs), obtaining multifunctional IONP@PPy nanocomposite which is further modified by the biocompatible polyethylene glycol (PEG) through a layer‐by‐layer method to acquire high stability in physiological solutions. Utilizing the optical and magnetic properties of the yielded IONP@PPy‐PEG nanoparticles, in vivo magnetic resonance (MR) and photoacoustic imaging of tumor‐bearing mice are conducted, revealing strong tumor uptake of those nanoparticles after intravenous injection. In vivo photothermal therapy is then designed and carried out, achieving excellent tumor ablation therapeutic effect in mice experiments. These results promise the use of multifunctional NIR‐absorbing organic‐inorganic hybrid nanomaterials, such as IONP@PPy‐PEG presented here, for potential applications in cancer theranostics.     

Imaging‐Guided pH‐Sensitive Photodynamic Therapy Using Charge Reversible Upconversion Nanoparticles under Near‐Infrared Light

Photodynamic therapy (PDT) based on upconversion nanoparticles (UCNPs) can effectively destroy cancer cells under tissue‐penetrating near‐infrared light (NIR) light. Herein, we synthesize manganese (Mn²⁺)‐doped UCNPs with strong red light emission at ca. 660 nm under 980 nm NIR excitation to activate Chlorin e6 (Ce6), producing singlet oxygen (¹O₂) to kill cancer cells. A layer‐by‐layer (LbL) self‐assembly strategy is employed to load multiple layers of Ce6 conjugated polymers onto UCNPs via electrostatic interactions. UCNPs with two layers of Ce6 loading (UCNP@2xCe6) are found to be optimal in terms of Ce6 loading and ¹O₂ generation. By further coating UCNP@2xCe6 with an outer layer of charge‐reversible polymer containing dimethylmaleic acid (DMMA) groups and polyethylene glycol (PEG) chains, we obtain a UCNP@2xCe6‐DMMA‐PEG nanocomplex, the surface of which is negatively charged and PEG coated under pH 7.4; this could be converted to have a positively charged naked surface at pH 6.8, significantly enhancing cell internalization of nanoparticles and increasing in vitro NIR‐induced PDT efficacy. We then utilize the intrinsic optical and paramagnetic properties of Mn²⁺‐doped UCNPs for in vivo dual modal imaging, and uncover an enhanced retention of UCNP@2xCe6‐DMMA‐PEG inside the tumor after intratumoral injection, owing to the slightly acidic tumor microenvironment. Consequently, a significantly improved in vivo PDT therapeutic effect is achieved using our charge‐reversible UCNP@2xCe6‐DMMA‐PEG nanoparticles. Finally, we further demonstrate the remarkably enhanced tumor‐homing of these pH‐responsive charge‐switchable nanoparticles in comparison to a control counterpart without pH sensitivity after systemic intravenous injection. Our results suggest that UCNPs with finely designed surface coatings could serve as smart pH‐responsive PDT agents promising in cancer theranostics.     

pH‐Responsive Cyanine‐Grafted Graphene Oxide for Fluorescence Resonance Energy Transfer‐Enhanced Photothermal Therapy

Stimuli‐responsive anticancer agents are of particular interest in the field of cancer therapy. Nevertheless, so far stimuli‐responsive photothermal agents have been explored with limited success for cancer photothermal therapy (PTT). In this work, as a proof‐of‐concept, a pH‐responsive photothermal nanoconjugate for enhanced PTT efficacy, in which graphene oxide (GO) with broad NIR absorbance and effective photothermal conversion efficiency is selected as a typical model receptor of fluorescence resonance energy transfer (FRET), and grafted cyanine dye (e.g., Cypate) acts as the donor of near‐infrared fluorescence (NIRF), is reported for the first time. The conjugate of Cypate‐grafted GO exhibits different conformations in aqueous solutions at various pH, which can trigger pH‐dependent FRET effect between GO and Cypate and thus induce pH‐responsive photothermal effect of GO‐Cypate. GO‐Cypate exhibits severe cell damage owing to the enhanced photothermal effect in lysosomes, and thus generate synergistic PTT efficacy with tumor ablation upon photoirradiation after a single‐dose intravenous injection. The photothermal nanoconjugate with broad NIR absorbance as the effective receptor of FRET can smartly convert emitted NIRF energy from donor cyanine dye into additional photothermal effect for improving PTT. These results suggest that the smart nanoconjugate can act as a promising stimuli‐responsive photothermal nanoplatform for cancer therapy.     

Z‐Scheme Heterojunction Functionalized Pyrite Nanosheets for Modulating Tumor Microenvironment and Strengthening Photo/Chemodynamic Therapeutic Effects

A Z‐scheme heterojunction with high electron–hole pairs separation efficacy and enhanced redox potentials exhibits tremendous potential in photonic theranostics, but still remains unexplored and challenging. Herein, novel 2D thermally oxidized pyrite nanosheets (TOPY NSs) with FeS₂ core and Fe₂O₃ shell are fabricated combining ball grinding and two‐step probe sonication assisted liquid exfoliation under different solution and air environments. The Fe₂O₃ shell and Fe³⁺/Fe²⁺ inside TOPY NSs can both damage the tumor microenvironment through glutathione consumption and O₂ production, and produce ·OH by Fenton reaction. More interestingly, a direct Z‐scheme heterojunction based on FeS₂ core and Fe₂O₃ shell is constructed, in which the electrons in the conduction band (CB) of Fe₂O₃ are recombined with the holes in the valence band (VB) of FeS₂, leaving stronger reduction/oxidation potentials in the CB of FeS₂ and the VB of Fe₂O₃. Under irradiation of a 650 nm laser, the generation of ·O₂^? from O₂ and ·OH from OH^? on the CB of FeS₂ and VB of Fe₂O₃, respectively, is largely enhanced. Furthermore, the NSs can be triggered by an 808 nm laser to generate local hyperthermia for photothermal therapy. Moreover, the fluorescent, photoacoustic, and photothermal imaging capabilities of the NSs allow multimodal imaging‐guided cancer treatment.     

Renal-Clearable Ultrasmall Polypyrrole Nanoparticles with Size-Regulated Property for Second Near-Infrared Light-Mediated Photothermal Therapy

The critical issue that hinders the translation of nanomaterials from basic research to clinical trials is their potential toxicity caused by long-term body retention. It is still a huge challenge to integrate renal-clearable and theranostic properties into one nanomedicine, especially exploring the nanomaterials with optical absorption in the second near-infrared light (NIR II) biowindow with deep penetration and less tissue scattering. Here, ultrasmall polypyrrole (PPy, ≈2 nm)-based theranostic agents via a facile and green one-step method, which exhibit fluorescence (FL)/photoacoustic (PA)/NIR II multimodal imaging, superior photostability, as well as high photothermal conversion efficiency of 33.35% at 808 nm and 41.97% at 1064 nm is developed. Importantly, these ultrasmall PPy-PEG nanoparticles (NPs) reveal abundant tumor accumulation and efficient renal clearance. Both in vitro and in vivo studies indicate that ultrasmall PPy-PEG NPs have excellent photothermal effect under NIR II laser irradiation that can effectively eliminate the tumors with extremely low systemic toxicity.     

Ultrastable and Biocompatible NIR‐II Quantum Dots for Functional Bioimaging

Fluorescence bioimaging in the second near‐infrared spectral region (NIR‐II, 1000–1700 nm) can provide advantages of high spatial resolution and large penetration depth, due to low light scattering. However, NIR‐II fluorophores simultaneously possessing high brightness, good stability, and biocompatibility are very rare. Hydrophobic NIR‐II emissive PbS@CdS quantum dots (QDs) are surface‐functionalized, via a silica and amphiphilic polymer (Pluronic F‐127) dual‐layer coating method. The as‐synthesized PbS@CdS@SiO₂@F‐127 nanoparticles (NPs) are aqueously dispersible and possess a quantum yield of ≈5.79%, which is much larger than those of most existing NIR‐II fluorophores. Thanks to the dual‐layer protection, PbS@CdS@SiO₂@F‐127 NPs show excellent chemical stability in a wide range of pH values. The biocompatibility of PbS@CdS@SiO₂@F‐127 NPs is studied, and the results show that the toxicity of the NPs in vivo could be minimal. PbS@CdS@SiO₂@F‐127 NPs are then utilized for in vivo and real‐time NIR‐II fluorescence microscopic imaging of mouse brain. The architecture of blood vessels is visualized and the imaging depth reaches 950 µm. Furthermore, in vivo NIR‐II fluorescence imaging of gastrointestinal tract is achieved, by perfusing PbS@CdS@SiO₂@F‐127 NPs into mice at a rather low dosage. This work illustrates the potential of ultrastable, biocompatible, and bright NIR‐II QDs in biomedical and clinical applications, which require deep tissue imaging.     

Fluorescent Block Copolymer‐MoS2 Nanocomposites for Real‐Time Photothermal Heating and Imaging

Novel self‐monitoring photothermal (PT) agents are developed using optothermally responsive block copolymer‐MoS₂ composites (BCP‐MoS₂), which enable simultaneous PT heating and imaging of temperature profiles. In particular, upon near‐infrared light exposure, PT energy from MoS₂ successfully increases local temperature and induces thermally activated conformational transitions of the BCP on MoS₂. This leads to fluorescent signal changes caused by distance‐dependent Förster resonance energy transfer between the BCP and MoS₂. Importantly, it is demonstrated that the use of BCP‐MoS₂ for PT heating and optical mapping is fully reversible with excellent stability. The detailed mechanism of the responsive behavior of BCP‐MoS₂ is elucidated by measurements of time‐resolved fluorescence and dynamic light scattering. In addition, the BCP‐MoS₂ system is integrated into organogel matrices to demonstrate its potential as aportable, self‐monitoring PT system suitable for biological and environmental applications.     

Bottom‐Up Preparation of Uniform Ultrathin Rhenium Disulfide Nanosheets for Image‐Guided Photothermal Radiotherapy

Facile preparation of multifunctional theranostic nanoplatforms with well‐controlled morphology and sizes remains an attractive in the area of nanomedicine. Here, a new kind of 2D transition metal dichalcogenide, rhenium disulfide (ReS₂) nanosheets, with uniform sizes, strong near‐infrared (NIR) light, and strong X‐ray attenuation, is successfully synthesized. After surface modification with poly(ethylene glycol) (PEG), the synthesized ReS₂‐PEG nanosheets are stable in various physiological solutions. In addition to their contrasts in photoacoustic imaging and X‐ray computed tomography imaging because of their strong NIR light and X‐ray absorptions, respectively, such ReS₂‐PEG nanosheets can also be tracked under nuclear imaging after chelator‐free labeling with radioisotope ions, ^99mTc⁴⁺. Efficient tumor accumulation of ReS₂‐PEG nanosheets is then observed after intravenous injection into tumor‐bearing mice under triple‐modal imaging. The combined in vivo photothermal radiotherapy is further conducted, achieving a remarkable synergistic tumor destruction effect. Finally, no obvious toxicity of ReS₂‐PEG nanosheets is observed from the treated mice within 30 d. This work suggests that such ultrathin ReS₂ nanosheets with well‐controlled morphology and uniform sizes may be a promising type of multifunctional theranostic agent for remotely triggered cancer combination therapy.     

Simultaneous Activation of Short‐Wave Infrared (SWIR) Light and Paramagnetism by a Functionalized Shell for High Penetration and Spatial Resolution Theranostics

Nanoparticle emitting short‐wave infrared (SWIR) light has received increased attention in the molecular imaging field due to its deeper tissue penetration, fast imaging, high sensitivity, and resolution. The simultaneously activated SWIR excited directly by an 808 nm laser and T₁‐weighted magnetic resonance imaging (MRI) signal are found in one single‐shell nanoparticle NaErF₄@NaGdF₄ (Er@Gd), which is used as a dual‐modality imaging contrast agent in vivo to accurately determine the position of tumors. The conjugated cypate is then aggregated on the surface of Er@Gd@SiO₂‐Cy/bovine serum albumin. With the guidance of dual modality imaging, photothermal therapy is effectively used to ablate tumors in a mouse model. The design of single‐shell nanomaterial activation of SWIR imaging and MRI signals is expected to provide a new strategy for high penetration and spatial resolution cancer theranostics.     

Semiconducting Nanocomposite with AIEgen‐Triggered Enhanced Photoluminescence and Photodegradation for Dual‐Modality Tumor Imaging and Therapy

Semiconducting polymer nanoparticles (SPNs) have potential in biological applications. While some SPNs have significant photothermal conversion efficiencies (PCEs) as photothermal and photoacoustic agents, other SPNs offer high fluorescence yields as photoluminescent agents. However, the energy balance distribution in SPNs inhibits their successful applications in photoluminescence/photoacoustic (PL/PA) dual‐modality imaging. Additionally, the ultrastability of SPNs in vivo may cause damage to organisms. This work reports nanocomposite semiconducting polymer and tetraphenylethene nanoparticles (STNPs) constructed by semiconducting polymers (SPs) and tetraphenylethene aggregation‐induced emission luminogens (TPE AIEgens). The SP SPC10 endows good photothermal conversion ability, and the AIEgen TPBM supports enhanced photoluminescence of the STNPs. The results show that the STNPs can act as PL/PA dual‐modality imaging agents. The signal‐to‐noise (S/N) ratio in the PL modality reaches 8.7, and the imaging depth in the PA modality is 5.8 mm. The SPC10 in the STNPs can be decomposed under 90 mW cm^?2 white light irradiation in 6 h without any other additional agents. Furthermore, the STNPs are sufficient for the treatment of xenograft 4T1 tumor‐bearing mice based on photothermal therapy. The nanocomposite STNPs achieve optimized dual‐modality PL/PA imaging and the AIEgen‐triggered in situ photodegradation of SPNs. These properties indicate the significant potential of STNPs in clinical diagnosis and noninvasive therapy.