An O2 Self‐Supplementing and Reactive‐Oxygen‐Species‐Circulating Amplified Nanoplatform via H2O/H2O2 Splitting for Tumor Imaging and Photodynamic Therapy

Conventional photodynamic therapy (PDT) has limited applications in clinical cancer therapy due to the insufficient O₂ supply, inefficient reactive oxygen species (ROS) generation, and low penetration depth of light. In this work, a multifunctional nanoplatform, upconversion nanoparticles (UCNPs)@TiO₂@MnO₂ core/shell/sheet nanocomposites (UTMs), is designed and constructed to overcome these drawbacks by generating O₂ in situ, amplifying the content of singlet oxygen (¹O₂) and hydroxyl radical (?OH) via water‐splitting, and utilizing 980 nm near‐infrared (NIR) light to increase penetration depth. Once UTMs are accumulated at tumor site, intracellular H₂O₂ is catalyzed by MnO₂ nanosheets to generate O₂ for improving oxygen‐dependent PDT. Simultaneously, with the decomposition of MnO₂ nanosheets and 980 nm NIR irradiation, UCNPs can efficiently convert NIR to ultraviolet light to activate TiO₂ and generate toxic ROS for deep tumor therapy. In addition, UCNPs and decomposed Mn²⁺ can be used for further upconversion luminescence and magnetic resonance imaging in tumor site. Both in vitro and in vivo experiments demonstrate that this nanoplatform can significantly improve PDT efficiency with tumor imaging capability, which will find great potential in the fight against tumor.     

Gold Nanoshell Nanomicelles for Potential Magnetic Resonance Imaging,Light‐Triggered Drug Release,and Photothermal Therapy

A novel multifunctional drug‐delivery platform is developed based on cholesteryl succinyl silane (CSS) nanomicelles loaded with doxorubicin, Fe₃O₄ magnetic nanoparticles, and gold nanoshells (CDF‐Au‐shell nanomicelles) to combine magnetic resonance (MR) imaging, magnetic‐targeted drug delivery, light‐triggered drug release, and photothermal therapy. The nanomicelles show improved drug‐encapsulation efficiency and loading level, and a good response to magnetic fields, even after the formation of the gold nanoshell. An enhancement for T₂‐weighted MR imaging is observed for the CDF‐Au‐shell nanomicelles. These nanomicelles display surface plasmon absorbance in the near‐infrared (NIR) region, thus exhibiting an NIR (808 nm)‐induced temperature elevation and an NIR light‐triggered and stepwise release behavior of doxorubicin due to the unique characteristics of the CSS nanomicelles. Photothermal cytotoxicity in vitro confirms that the CDF‐Au‐shell nanomicelles cause cell death through photothermal effects only under NIR laser irradiation. Cancer cells incubated with CDF‐Au‐shell nanomicelles show a significant decrease in cell viability only in the presence of both NIR irradiation and a magnetic field, which is attributed to the synergetic effects of the magnetic‐field‐guided drug delivery and the photothermal therapy. Therefore, such multicomponent nanomicelles can be developed as a smart and promising nanosystem that integrates multiple capabilities for effective cancer diagnosis and therapy.     

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.     

Tumor Microenvironment‐Responsive Mesoporous MnO2‐Coated Upconversion Nanoplatform for Self‐Enhanced Tumor Theranostics

The insufficient blood flow and oxygen supply in solid tumor cause hypoxia, which leads to low sensitivity of tumorous cells and thus causing poor treatment outcome. Here, mesoporous manganese dioxide (mMnO₂) with ultrasensitive biodegradability in a tumor microenvironment (TME) is grown on upconversion photodynamic nanoparticles for not only TME‐enhanced bioimaging and drug release, but also for relieving tumor hypoxia, thereby markedly improving photodynamic therapy (PDT). In this nanoplatform, mesoporous silica coated upconversion nanoparticles (UCNPs@mSiO₂) with covalently loaded chlorin e6 are obtained as near‐infrared light mediated PDT agents, and then a mMnO₂ shell is grown via a facile ultrasonic way. Because of its unique mesoporous structure, the obtained nanoplatform postmodified with polyethylene glycol can load the chemotherapeutic drug of doxorubicin (DOX). When used for antitumor application, the mMnO₂ degrades rapidly within the TME, releasing Mn²⁺ ions, which couple with trimodal (upconversion luminescence, computed tomography (CT), and magnetic resonance imaging) imaging of UCNPs to perform a self‐enhanced imaging. Significantly, the degradation of mMnO₂ shell brings an efficient DOX release, and relieve tumor hypoxia by simultaneously inducing decomposition of tumor endogenous H₂O₂ and reduction of glutathione, thus achieving a highly potent chemo‐photodynamic therapy.     

Neuroendocrine Tumor‐Targeted Upconversion Nanoparticle‐Based Micelles for Simultaneous NIR‐Controlled Combination Chemotherapy and Photodynamic Therapy,and Fluorescence Imaging

Although neuroendocrine tumors (NETs) are slow growing, they are frequently metastatic at the time of discovery and no longer amenable to curative surgery, emphasizing the need for the development of other treatments. In this study, multifunctional upconversion nanoparticle (UCNP)‐based theranostic micelles are developed for NET‐targeted and near‐infrared (NIR)‐controlled combination chemotherapy and photodynamic therapy (PDT), and bioimaging. The theranostic micelle is formed by individual UCNP functionalized with light‐sensitive amphiphilic block copolymers poly(4,5‐dimethoxy‐2‐nitrobenzyl methacrylate)‐polyethylene glycol (PNBMA‐PEG) and Rose Bengal (RB) photosensitizers. A hydrophobic anticancer drug, AB3, is loaded into the micelles. The NIR‐activated UCNPs emit multiple luminescence bands, including UV, 540 nm, and 650 nm. The UV peaks overlap with the absorption peak of photocleavable hydrophobic PNBMA segments, triggering a rapid drug release due to the NIR‐induced hydrophobic‐to‐hydrophilic transition of the micelle core and thus enabling NIR‐controlled chemotherapy. RB molecules are activated via luminescence resonance energy transfer to generate ¹O₂ for NIR‐induced PDT. Meanwhile, the 650 nm emission allows for efficient fluorescence imaging. KE108, a true pansomatostatin nonapeptide, as an NET‐targeting ligand, drastically increases the tumoral uptake of the micelles. Intravenously injected AB3‐loaded UCNP‐based micelles conjugated with RB and KE108—enabling NET‐targeted combination chemotherapy and PDT—induce the best antitumor efficacy.     

Enhanced Antitumor Efficacy by 808 nm Laser‐Induced Synergistic Photothermal and Photodynamic Therapy Based on a Indocyanine‐Green‐Attached W18O49 Nanostructure

A novel nanoplatform based on tungsten oxide (W₁₈O₄₉, WO) and indocyanine green (ICG) for dual‐modal photothermal therapy (PTT) and photodynamic therapy (PDT) has been successfully constructed. In this design, the hierarchical unique nanorod‐bundled W₁₈O₄₉ nanostructures play roles in being not only as an efficient photothermal agent for PTT but also as a potential nanovehicle for ICG molecules via electrostatic adsorption after modified with trimethylammonium groups on their surface. It is found that the ability of ICG to produce cytotoxic reactive oxygen species for PDT is well maintained after being attached on the WO, thus the as‐obtained WO@ICG can achieve a synergistic effect of combined PTT and PDT under single 808 nm near‐infrared (NIR) laser excitation. Notably, compared with PTT or PDT alone, the enhanced HeLa cells lethality of the 808 nm laser triggered dual‐modal therapy is observed. The in vivo animal experiments have shown that WO@ICG has effective solid tumor ablation effect with 808 nm NIR light irradiation, revealing the potential of these nanocomposites as a NIR‐mediated dual‐modal therapeutic platform for cancer treatment.     

Fabricating Aptamer‐Conjugated PEGylated‐MoS2/Cu1.8S Theranostic Nanoplatform for Multiplexed Imaging Diagnosis and Chemo‐Photothermal Therapy of Cancer

Fabricating theranostic nanoparticles combining multimode disease diagnosis and therapeutic has become an emerging approach for personal nanomedicine. However, the diagnostic capability, biocompatibility, and therapeutic efficiency of theranostic nanoplatforms limit their clinic widespread applications. Targeting to the theme of accurate diagnosis and effective therapy of cancer cells, a multifunctional nanoplatform of aptamer and polyethylene glycol (PEG) conjugated MoS₂ nanosheets decorated with Cu_1.8S nanoparticles (ATPMC) is developed. The ATPMC nanoplatform accomplishes photoluminescence imaging, photoacoustic imaging, and photothermal imaging for in vitro and in vivo tumor cells imaging diagnosis. Meanwhile, the ATPMC nanoplatform facilitates selective delivery of gene probe to detect intracellular microRNA aberrantly expressed in cancer cells and anticancer drug doxorubicin (DOX) for chemotherapy. Moreover, the synergistic interaction of MoS₂ and Cu_1.8S renders the ATPMC nanoplatform with superb photothermal conversion efficiency. The ATPMC nanoplatform loaded with DOX displays near‐infrared laser‐induced programmed chemotherapy and advanced photothermal therapy, and the targeted chemo‐photothermal therapy presents excellent antitumor efficiency.     

Cypate‐Conjugated Porous Upconversion Nanocomposites for Programmed Delivery of Heat Shock Protein 70 Small Interfering RNA for Gene Silencing and Photothermal Ablation

Synergistic therapy is an accepted method of enhancing the efficacy of cancer therapies. In this study, cypate‐conjugated porous NaLuF₄ doped with Yb³⁺, Er³⁺, and Gd³⁺ is synthesized and its potential for upconversion luminescence/magnetic resonance dual‐modality molecular imaging for guiding oncotherapy is tested. Loading cypate‐conjugated upconversion nanoparticles (UCNP‐cy) with small interfering RNA gene against heat shock protein 70 (UCNP‐cy‐siRNA) enhances the cell damage. UCNP‐cy‐siRNA exhibits remarkable antitumor efficacy in vivo as a result of the synergistic effects of gene silencing and photothermal therapy, with low drug dose and minimal side effects. This result thus provides an explicit strategy for developing next‐generation multifunctional nanoplatforms for multimodal imaging‐guided synergistic oncotherapy.     

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.     

Pegylated Composite Nanoparticles Containing Upconverting Phosphors and meso‐Tetraphenyl porphine (TPP) for Photodynamic Therapy

The utilization of upconverting nanophosphors (UCNP) for photodynamic therapy (PDT) has gained significant interests due to its ability to convert deep‐penetrating near‐infra red (NIR) light (i.e., 978 nm) to visible light. Previous attempts to co‐localize UCNPs with photosensitizers suffer from low photo­sensitizer loading and problems with nanoparticle aggregation. Here, the preparation of a novel composite nanoparticle formulation comprising 100 nm β?NaYF₄:Yb³⁺,Er³⁺ UCNPs, and meso‐tetraphenyl porphine (TPP) photo­sensitizer, stabilized by biocompatible poly(ethylene glycol‐block‐(dl )lactic acid) block copolymers (PEG‐b‐PLA) is presented. A photosensitizer loading of 10 wt% with respect to UCNP crystal was achieved via the Flash NanoPrecipitation (FNP) process. A sterically stabilizing PEG layer on the composite nanoparticle surface prevents nanoparticle aggregation and ensures nanoparticle stability in water, PBS buffer, and culture medium containing serum proteins, resulting in nanoparticle suitable for in vivo applications. Based on in vitro studies utilizing HeLa cervical cancer cell lines, the composite nanoparticles are shown to exhibit low dark toxicity and efficient cancer cell‐killing activity upon NIR excitation. Exposure with 134 W cm^?2 of 978 nm light for 45 min resulted in 75% HeLa cell death. This is the first quantification of the cell‐killing capabilities of the UCNP/TPP composite nanoparticles formulated for photodynamic therapy.     

Remarkable NIR Enhancement of Multifunctional Nanoprobes for In Vivo Trimodal Bioimaging and Upconversion Optical/T2‐Weighted MRI‐Guided Small Tumor Diagnosis

Effective nanoprobes and contrast agents are urgently sought for early‐stage cancer diagnosis. Upconversion nanoparticles (UCNPs) are considerable alternatives for bioimaging, cancer diagnosis, and therapy. Yb³⁺/Tm³⁺ co‐doping brings both emission and excitation wavelengths into the near‐infrared (NIR) region, which is known as “optical transmission window” and ideally suitable for bioimaging. Here, NIR emission intensity is remarkably enhanced by 113 times with the increase of Yb³⁺ concentration from 20% to 98% in polyethylene glycol (PEG) modified NaYF₄:Yb³⁺/Tm³⁺ UCNPs. PEG‐UCNPs‐5 (98% Yb³⁺) can act as excellent nanoprobes and contrast agents for trimodal upconversion (UC) optical/CT/T₂‐weighted magnetic resonance imaging (MRI). In addition, the enhanced detection of lung in vivo long‐lasting tracking, as well as possible clearance mechanism and excretion routes of PEG‐UCNPs‐5 have been demonstrated. More significantly, a small tumor down to 4 mm is detected in vivo via intravenous injection of these nanoprobes under both UC optical and T₂‐weighted MRI modalities. PEG‐UCNPs‐5 can emerge as bioprobes for multi‐modal bioimaging, disease diagnosis, and therapy, especially the early‐stage tumor diagnosis.     

NIR‐II Light Activated Photosensitizer with Aggregation‐Induced Emission for Precise and Efficient Two‐Photon Photodynamic Cancer Cell Ablation

Near infrared (NIR) light excitable photosensitizers are highly desirable for photodynamic therapy with deep penetration. Herein, a NIR‐II light (1200 nm) activated photosensitizer TQ‐BTPE is designed with aggregation‐induced singlet oxygen (¹O₂) generation for two‐photon photodynamic cancer cell ablation. TQ‐BTPE shows good two‐photon absorption and bright aggregation‐induced NIR‐I emission upon NIR‐II laser excitation. The ¹O₂ produced by TQ‐BTPE in an aqueous medium is much more efficient than that of commercial photosensitizer Ce6 under white light irradiation. Upon NIR‐II excitation, the two‐photon photosensitization of TQ‐BTPE is sevenfold higher than that of Ce6. The TQ‐BTPE molecules internalized by HeLa cells are mostly located in lysosomes as small aggregate dots with homogeneous distribution inside the cells, which favors efficient photodynamic cell ablation. The two‐photon photosensitization of TQ‐BTPE upon NIR‐I and NIR‐II excitation shows higher ¹O₂ generation efficiency than under NIR‐I excitation owing to the larger two‐photon absorption cross section at 920 nm. However, NIR‐II light exhibits better biological tissue penetration capability after passing through a fresh pork tissue, which facilitates stronger two‐photon photosensitization and better cancer cell ablation performance. This work highlights the promise of NIR‐II light excitable photosensitizers for deep‐tissue photodynamic therapy.     

Atomic‐Level Passivation of Individual Upconversion Nanocrystal for Single Particle Microscopic Imaging

Lanthanide‐doped upconversion nanoparticles (UCNPs) have significant applications for single‐molecule probes and high‐resolution display. However, one of their major hurdles is the weak luminescence, and this remains a grand challenge to achieve at the single‐particle level. Here, 484‐fold luminescence enhancement in LuF₃:Yb³⁺, Er³⁺ rhombic flake UCNPs is achieved, thanks to the Yb³⁺‐mediated local photothermal effect, and their original morphology, size, and good dispersibility are well preserved. These data show that the surface atomic structure of UCNPs as well as transfer from amorphous to ordered crystal structure is modulated by making use of the local photothermal conversion that is generated by the directional absorption of 980 nm light by Yb³⁺ ions. The confocal luminescence images obtained by super‐resolution stimulated emission depletion also show the great enhancement of individual LuF₃:Yb³⁺, Er³⁺ nanoparticles; the high signal‐to‐noise ratio images indicate that the laser treatment technology opens the door for single particle imaging and practical application.     

SnTe@MnO2‐SP Nanosheet–Based Intelligent Nanoplatform for Second Near‐Infrared Light–Mediated Cancer Theranostics

Near infrared light, especially the second near‐infrared light (NIR II) biowindows with deep penetration and high sensitivity are widely used for optical diagnosis and phototherapy. Here, a novel kind of 2D SnTe@MnO₂‐SP nanosheet (NS)‐based nanoplatform is developed for cancer theranostics with NIR II‐mediated precise optical imaging and effective photothermal ablation of mouse xenografted tumors. The 2D SnTe@MnO₂‐SP NSs are fabricated via a facile method combining ball‐milling and liquid exfoliation for synthesis of SnTe NSs, and surface coating MnO₂ shell and soybean phospholipid (SP). The ultrathin SnTe@MnO₂‐SP NSs reveal notably high photothermal conversion efficiency (38.2% in NIR I and 43.9% in NIR II). The SnTe@MnO₂‐SP NSs inherently feature tumor microenvironment (TME)‐responsive biodegradability, and the main metabolite TeO₃^2? shows great antitumor effect, coupling synergetic chemotherapy for cancer. Moreover, the SnTe@MnO₂‐SP NSs also exhibit great potential for fluorescence, photoacoustic (PA), and photothermal imaging agents in the NIR II biowindow with much higher resolution and sensitivity. This is the first report, as far as is known, with such an inorganic nanoagent setting fluorescence/PA/photothermal imaging and photothermal therapy in NIR II biowindow and TME‐responsive biodegradability rolled into one, which provide insight into the clinical potential for cancer theranostics.     

Solution‐Processable Near‐Infrared–Responsive Composite of Perovskite Nanowires and Photon‐Upconversion Nanoparticles

Organolead halide perovskites (OHPs) have shown unprecedented potentials in optoelectronics. However, the inherent large bandgap has restrained its working wavelength within 280–800 nm, while light at other regions, e.g., near‐infrared (NIR), may cause drastic thermal heating effect that goes against the duration of OHP devices, if not properly exploited. Herein, a solution processable and large‐scale synthesis of multifunctional OHP composites containing lanthanide‐doped upconversion nanoparticles (UCNPs) is reported. Upon NIR illumination, the upconverted photons from UCNPs at 520–550 nm can be efficiently absorbed by closely surrounded OHP nanowires (NWs) and photocurrent is subsequently generated. The narrow full width at half maximum of the absorption of rare earth ions (Yb³⁺ and Er³⁺) has ensured high‐selective NIR response. Lifetime characterizations have suggested that Förster resonance energy transfer with an efficiency of 28.5% should be responsible for the direct energy transfer from UCNPs to OHP NWs. The fabricated proof‐of‐concept device has showcased perfect response to NIR light at 980 and 1532 nm, which has paved new avenues for applications of such composites in remote control, distance measurement, and stealth materials.     

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.     

Poly(Acrylic Acid) Modification of Nd3+‐Sensitized Upconversion Nanophosphors for Highly Efficient UCL Imaging and pH‐Responsive Drug Delivery

In this work, a simple method is demonstrated for the synthesis of multifunctional core–shell nanoparticles NaYF₄:Yb,Er@NaYF₄:Yb@NaNdF₄:Yb@NaYF₄:Yb@PAA (labeled as Er@Y@Nd@Y@PAA or UCNP@PAA), which contain a highly effective 808‐nm‐to‐visible UCNP core and a thin shell of poly(acrylic acid) (PAA) to achieve upconversion bioimaging and pH‐sensitive anticancer chemotherapy simultaneously. The core–shell Nd³⁺‐sensitized UCNPs are optimized by varying the shell number, core size, and host lattices. The final optimized Er@Y@Nd@Y nanoparticle composition shows a significantly improved upconversion luminescence intensity, that is, 12.8 times higher than Er@Y@Nd nanoparticles. After coating the nanocomposites with a thin layer of PAA, the resulting UCNP@PAA nanocomposite perform well as a pH‐responsive nanocarrier and show clear advantages over UCNP@mSiO₂, which are evidenced by in vitro/in vivo experiments. Histological analysis also reveals that no pathological changes or inflammatory responses occur in the heart, lungs, kidneys, liver, and spleen. In summary, this study presents a major step forward towards a new therapeutic and diagnostic treatment of tumors by using 808‐nm excited UCNPs to replace the traditional 980‐nm excitation.     

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.     

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.     

Mesoporous Polydopamine Carrying Manganese Carbonyl Responds to Tumor Microenvironment for Multimodal Imaging‐Guided Cancer Therapy

Multifunctional nanodrugs integrating multiple therapeutic and imaging functions may find tremendous biomedical applications. However, the development of a simple yet potent theranostic nanosystem with a high payload and microenvironment responsiveness enhancing imaging‐guided cancer therapy is still a great challenge. Herein, a kind of MnCO‐entrapped mesoporous polydopamine nanoparticles are developed, which reach a 1.5 mg payload per gram carrier and exhibit marked theranostic capability through effective CO/Mn²⁺ generation and photothermal conversion inside the H⁺ and H₂O₂‐enriched tumor microenvironment, for a magnetic resonance/photoacoustic bimodal imaging‐guided tumor therapy. The multifunctional nanosystem exhibits a biocompatibility highly desirable for in vivo application and superior performance in inhibiting tumor growth and recurrence via combination CO and photothermal therapy.