Tumor Microenvironment Responsive Single-Atom Nanozymes for Enhanced Antitumor Therapy.

Single-atom nanozymes (SAzymes) with specific response to the unique tumor microenvironment (TME) feature providing 100 % metal atoms utilization for high-efficient enzyme-catalyzed therapy and accurate template for the study of therapeutic mechanisms. In this review, we first introduce the various synthetic strategies of SAzymes, and the TME-responsive SAzymes activities. Next, the TME-responsive enhanced antitumor therapeutic approaches based on the enzymatic activities of SAzymes are summarized, and the corresponding therapy mechanisms are elaborated. Subsequently, a concise but concentrated summary, and the challenges and opportunities for the future design and engineering of SAzyme are outlined. As a new discipline, SAzymes have vast space for development in enhanced antitumor therapy. This timely review provides guidance and constructive suggestions for the future of SAzymes.

Cu Single Atom Nanozyme Based High-Efficiency Mild Photothermal Therapy through Cellular Metabolic Regulation.

Upregulation of heat shock proteins (HSPs) drastically compromises the treatment effect of mild photothermal therapy (PTT). Herein, we designed a polyporous Cu single atom nanozyme (Cu SAzyme) loaded with licogliflozin (LIK066) for HSP-silencing induced mild PTT. On one hand, LIK066 inhibits glucose uptake by shutting sodium-dependent glucose transporter (SGLT) "valve", effectively blocking the energy source for adenosine triphosphate (ATP) generation. Without sufficient energy, cancer cells cannot synthesize HSPs. On the other hand, Cu SAzyme presents extraordinary multienzyme activities to induce reactive oxygen species (ROS) storm formation, which can damage the existing HSPs in cancer cells. Through a two-pronged strategy of SGLT inhibitor and ROS storm, LIK066-loaded Cu SAzyme shows high efficiency for comprehensive removal of HSPs to realize mild PTT.

A Multifunctional Nanovaccine based on L-Arginine-Loaded Black Mesoporous Titania: Ultrasound-Triggered Synergistic Cancer Sonodynamic Therapy/Gas Therapy/Immunotherapy with Remarkably Enhanced Efficacy.

In order to achieve better antitumor therapeutic efficacy and inhibit tumor metastasis, a multifunctional nanovaccine based on L-arginine (LA)-loaded black mesoporous titania (BMT) is fabricated. In this system, LA is utilized as the exogenous NO supplementation for gas therapy, and BMT is served as acoustic sensitizer for sonodynamic therapy. The ultrasound (US) as the exogenous stimulus can simultaneously trigger BMT and LA to produce singlet oxygen (1 O2 ) and NO gas at tumor sites, respectively. Interestingly, 1 O2 from US-excited BMT can promote the oxidation of LA to produce more NO. The high concentration of 1 O2 and NO in cancer cell can cause intracellular strong oxidative stress level and DNA double-strand breaks to induce cancer cell apoptosis ultimately. The US-triggered BMT@LA "nanovaccine" combining with immune checkpoint inhibitor PD-L1 antibody (αPD-L1) can induce strong antitumor immune response thus effectively killing primary tumors and further inhibiting metastatic tumors. Hence, BMT@LA-based "nanovaccine" combining with αPD-L1 checkpoint blockade treatment can realize synergetic sonodynamic/gas/immunotherapy with enhanced antitumor therapeutic effects.

Single-Atom Pd Nanozyme for Ferroptosis-Boosted Mild-Temperature Photothermal Therapy.

Photothermal therapy (PTT) is an extremely promising tumor therapeutic modality. However, excessive heat inevitably injures normal tissues near tumors, and the damage to cancer cells caused by mild hyperthermia is easily repaired by stress-induced heat shock proteins (HSPs). Thus, maximizing the PTT efficiency and minimizing the damage to healthy tissues simultaneously by adopting appropriate therapeutic temperatures is imperative. Herein, an innovative strategy is reported: ferroptosis-boosted mild PTT based on a single-atom nanozyme (SAzyme). The Pd SAzyme with atom-economical utilization of catalytic centers exhibits peroxidase (POD) and glutathione oxidase (GSHOx) mimicking activities, and photothermal conversion performance, which can result in ferroptosis featuring the up-regulation of lipid peroxides (LPO) and reactive oxygen species (ROS). The accumulation of LPO and ROS provides a powerful approach for cleaving HSPs, which enables Pd SAzyme-mediated mild-temperature PTT.

Cu2 MoS4 /Au Heterostructures with Enhanced Catalase-Like Activity and Photoconversion Efficiency for Primary/Metastatic Tumors Eradication by Phototherapy-Induced Immunotherapy.

Photoimmunotherapy can not only effectively ablate the primary tumor but also trigger strong antitumor immune responses against metastatic tumors by inducing immunogenic cell death. Herein, Cu2 MoS4 (CMS)/Au heterostructures are constructed by depositing plasmonic Au nanoparticles onto CMS nanosheets, which exhibit enhanced absorption in near-infrared (NIR) region due to the newly formed mid-gap state across the Fermi level based on the hybridization between Au 5d orbitals and S 3p orbitals, thus resulting in more excellent photothermal therapy and photodynamic therapy (PDT) effect than single CMS upon NIR laser irradiation. The CMS and CMS/Au can also serve as catalase to effectively relieve tumor hypoxia, which can enhance the therapeutic effect of O2 -dependent PDT. Notably, the NIR laser-irradiated CMS/Au can elicit strong immune responses via promoting dendritic cells maturation, cytokine secretion, and activating antitumor effector T-cell responses for both primary and metastatic tumors eradication. Moreover, CMS/Au exhibits outstanding photoacoustic and computed tomography imaging performance owing to its excellent photothermal conversion and X-ray attenuation ability. Overall, the work provides an imaging-guided and phototherapy-induced immunotherapy based on constructing CMS/Au heterostructures for effectively tumor ablation and cancer metastasis inhibition.

BMP-2-Loaded HAp:Ln3+ (Ln = Yb, Er, Gd) Nanorods with Dual-Mode Imaging for Efficient MC3t3-E1 Cell Differentiation Regulation.

Effective bone tissue reconstitution improves the treatment success rate of dental implantation and preserves natural teeth during periodontal tissue repair. Hydroxyapatite (HAp) has received much attention in bone remodeling field because its mineralized structure is similar to that of the natural bone tissue. For this reason, it has been used as a carrier for growth factors. Although HAp possesses outstanding biomedical properties, its capacity of loading and releasing bone growth factors and promoting osteogenesis is not well understood. In this study, Ln3+ (Ln = Yb3+, Er3+, Gd3+)-doped HAp (HAp:Ln3+) nanorods were synthesized by one-step hydrothermal method. To improve its biocompatibility and surface properties, bone morphogenetic protein-2 (BMP-2) was loaded onto the surface of HAp:Ln3+ nanorods. The results showed that BMP-2 incorporation promoted bone formation and enhanced the expression of early bone-related gene and protein (RunX2, SP7, OPN). In addition, Yb3+- and Er3+-doped HAp nanorods were examined by upconversion luminescence with 980 nm near-infrared laser irradiation to monitor the delivery position of BMP-2 protein. Furthermore, due to the positive magnetism correlated with the concentration of Gd3+, HAp:Ln3+ with enhanced contrast brightening can be deemed as T1 MIR contrast agents. These findings indicate that HAp doped with rare-earth ions and loaded with BMP-2 has the potential to promote bone tissue repair and execute dual-mode imaging.

Recent Progress in Near Infrared Light Triggered Photodynamic Therapy.

Nowadays, photodynamic therapy (PDT) is under the research spotlight as an appealing modality for various malignant tumors. Compared with conventional PDT treatment activated by ultraviolet or visible light, near infrared (NIR) light-triggered PDT possessing deeper penetration to lesion area and lower photodamage to normal tissue holds great potential for in vivo deep-seated tumor. In this review, recent research progress related to the exploration of NIR light responsive PDT nanosystems is summarized. To address current obstacles of PDT treatment and facilitate the effective utilization, several innovative strategies are developed and introduced into PDT nanosystems, including the conjugation with targeted moieties, O2 self-sufficient PDT, dual photosensitizers (PSs)-loaded PDT nanoplatform, and PDT-involved synergistic therapy. Finally, the potential challenges as well as the prospective for further development are also discussed.

Stimuli-responsive nanocomposites for magnetic targeting synergistic multimodal therapy and T1/T2-weighted dual-mode imaging.

Anticancer drug doxorubicin hydrochloride (DOX)-loaded photothermal nanocomposite MnFe2O4@mSiO2 with magnetic targeting and T1/T2-weighted dual-mode magnetic resonance imaging of MnFe2O4 core and NIR/pH-coupling sensitive mesoporous silica shell nanocarriers was designed and synthesized successfully. The anticancer drug DOX can be absorbed into mesoporous layer of MnFe2O4@mSiO2 nanocomposite, which shows obvious photothermal/chemo dual-modal synergistic therapies triggered by NIR/pH. Under 808 nm irradiation, MnFe2O4 can transform light into thermo, which can not only ablate tumor cells directly but also promote chemotherapy drugs releasing from mesoporous layer to kill tumor cells. The lower pH can also promote DOX releasing from mesoporous layer to enhance tumor inhibitory effect. It is confirmed that biocompatible DOX-MnFe2O4@mSiO2 nanocomposites can act as a potential multifunctional platform for effective magnetic targeting photothermal/chemo dual-modal synergistic therapies with enhanced anti-tumor efficacy and T1/T2-weighted dual-mode magnetic resonance imaging (MRI) applications in vivo.

Multifunctional hydroxyapatite/Na(Y/Gd)F4:Yb3+,Er3+ composite fibers for drug delivery and dual modal imaging.

Porous hydroxyapatite (HAp) composite fibers functionalized with up-conversion (UC) luminescent and magnetic Na(Y/Gd)F4:Yb(3+),Er(3+) nanocrystals (NCs) have been fabricated via electrospinning. After transferring hydrophobic oleic acid-capped Na(Y/Gd)F4:Yb(3+),Er(3+) NCs into aqueous solution, these water-dispersible NCs were dispersed into precursor electrospun solution containing CTAB. Na(Y/Gd)F4:Yb(3+),Er(3+)@HAp composite fibers were fabricated by the high temperature treatment of the electrospun Na(Y/Gd)F4:Yb(3+),Er(3+) NCs decorated precursor fibers. The biocompatibility test on MC 3T3-E1 cells using MTT assay shows that the HAp composite fibers have negligible cytotoxity, which reveals the HAp composite fibers could be a drug carrier for drug delivery. Because the contrast brightening is enhanced at increased concentrations of Gd(3+), the HAp composite fibers can serve as T1 magnetic resonance imaging contrast agents. In addition, the composites uptaken by MC 3T3-E1 cells present the UC luminescent emission of Er(3+) under the excitation of a 980 nm near-infrared laser. The above findings reveal Na(Y/Gd)F4:Yb(3+),Er(3+)@HAp composite fibers have potential applications in drug storage/release and magnetic resonance/UC luminescence imaging.

Efficient gene delivery and multimodal imaging by lanthanide-based upconversion nanoparticles.

Nanoparticles have been explored as nonviral gene carriers for years because of the simplicity of surface modification and lack of immune response. Lanthanide-based upconversion nanoparticles (UCNPs) are becoming attractive candidates for biomedical applications in virtue of their unique optical properties and multimodality imaging ability. Here, we report a UCNPs-based structure with polyethylenimine coating for both efficient gene transfection and trimodality imaging. Cytotoxicity tests demonstrated that the nanoparticles exhibited significantly decreased cytotoxicity compared to polyethylenimine polymer. Further, in vitro studies revealed that the gene carriers are able to transfer the enhanced green fluorescence protein (EGFP) plasmid DNA into Hela cells in higher transfection efficiency than PEI. Gene silencing was also examined by delivering bcl-2 siRNA into Hela cells, resulting in significant downregulation of target bcl-2 mRNA. More importantly, we demonstrated the feasibility of upconversion gene carriers to serve as effective contrast agents for MRI/CT/UCL trimodality imaging both in vitro and in vivo. The facile fabrication process, great biocompatibility, enhanced gene transfection efficiency, and great bioimaging ability can make it promising for application in gene therapy.

Morphology control and multicolor up-conversion luminescence of GdOF:Yb3+/Er3+, Tm3+, Ho3+ nano/submicrocrystals.

In this paper, well defined GdOF:Yb(3+)/Er(3+), Tm(3+), Ho(3+) nano/submicrocrystals with multiform morphologies were prepared via the urea-based precipitation method without using any surfactants. The morphologies of the GdOF products, including spindles and spheres with different sizes (30-550 nm), could be easily modulated by changing the fluorine sources, and the possible formation mechanism has been presented. XRD, FT-IR, SEM, TEM, as well as up-conversion (UC) photoluminescence spectra were used to characterize the prepared samples. Under 980 nm NIR excitation, the relative emission intensities and emission colors of Yb(3+)/Er(3+), Yb(3+)/Tm(3+) and Yb(3+)/Ho(3+) doped GdOF could be precisely adjusted over a wide range by tuning the Yb(3+) doping concentration. The strategies for color tuning of UC emission proposed in the current system may be helpful to achieve efficient multicolor luminescence under 980 nm laser excitation. In addition, the corresponding UC mechanisms in the co-doping GdOF systems were analyzed in detail based on the emission spectra and the plot of luminescence intensity to pump power.

In vivo multimodality imaging and cancer therapy by near-infrared light-triggered trans-platinum pro-drug-conjugated upconverison nanoparticles.

Controlling anticancer drug activity and release on demand is very significant in cancer therapy. The photoactivated platinum(IV) pro-drug is stable in the dark and can be activated by UV light. In this study, we develop a multifunctional drug delivery system combining upconversion luminescence/magnetic resonance/computer tomography trimodality imaging and NIR-activated platinum pro-drug delivery. We use the core-shell structured upconversion nanoparticles to convert the absorbed NIR light into UV to activate the trans-platinum(IV) pro-drug, trans,trans,trans-[Pt(N3)2(NH3)(py)(O2CCH2CH2COOH)2]. Compared with using the UV directly, the NIR has a higher tissue penetration depth and is less harmful to health. Meanwhile, the upconversion nanoparticles can effectively deliver the platinum(IV) pro-drugs into the cells by endocytosis. The mice treated with pro-drug-conjugated nanoparticles under near-infrared (NIR) irradiation demonstrated better inhibition of tumor growth than that under direct UV irradiation. This multifunctional nanocomposite could be used as multimodality bioimaging contrast agents and transducers by converting NIR light into UV for control of drug activity in practical cancer therapy.

Multiwalled carbon nanotubes and NaYF4:Yb3+/Er3+ nanoparticle-doped bilayer hydrogel for concurrent NIR-triggered drug release and up-conversion luminescence tagging.

Bilayer thermosensitive P(NIPAm-co-AAm) hydrogel discs were prepared by a facile UV light initiation process from N-isopropylacrylamide (NIPAm) and acrylamide (AAm) monomers' cross-linking copolymerization. Poly(ethylene glycol) (PEG) as a pore-forming agent was added in order to form a porous structure and improve the water content in the hydrogel. Functional materials of NaYF4:Yb(3+)/Er(3+) nanoparticles and multiwalled carbon nanotubes (MWCNTs) were incorporated into different layers of the P(NIPAm-co-AAm) hydrogel for the purpose of up-conversion luminescence labeling and the NIR light antenna effect, respectively. Significantly improved drug release from composite hydrogels was achieved in response to 980 nm NIR light irradiation by using lysozyme as a macromolecular drug. The multifunctional hydrogel reported here provides a platform for simultaneous NIR luminescence labeling and NIR-driven drug release.

Electrospun upconversion composite fibers as dual drugs delivery system with individual release properties.

Novel multifunctional poly(ε-caprolactone)-gelatin encapsulating upconversion core/shell silica nanoparticles (NPs) composite fibers as dual drugs delivery system (DDDS), with indomethacin (IMC) and doxorubicin (DOX) releasing in individual release properties, have been designed and fabricated via electrospinning process. Uniform and monodisperse upconversion (UC) luminescent NaYF4:Yb(3+), Er(3+) nanocrystals (UCNCs) were encapsulated with mesoporous silica shells, resulting in the formation of core/shell structured NaYF4:Yb(3+), Er(3+)@mSiO2 (UCNCs@mSiO2) NPs, which can be performed as DOX delivery carriers. These UCNCs@mSiO2 NPs loading DOX then were dispersed into the mixture of poly(ε-caprolactone) (PCL) and gelatin-based electrospinning solution containing IMC, followed by the preparation of dual drug-loaded composite fibers (DDDS) via electrospinning method. The drugs release profiles of the DDDS were measured, and the results indicated that the IMC and DOX released from the electrospun composite fibers showed distinct properties. The IMC in the composite fibers presented a fast release manner, while DOX showed a sustained release behavior. Moreover, the UC luminescent intensity ratios of (2)H(11/2)/(4)S(3/2)-(4)I(15/2) to (4)F(9/2)-(4)I(15/2) from Er(3+) vary with the amounts of DOX in the system, and thus drug release can be tracked and monitored by the luminescence resonance energy transfer (LRET) mechanism.

Mild-Photothermal Effect Induced High Efficiency Ferroptosis-Boosted-Cuproptosis Based on Cu2 O@Mn3 Cu3 O8 Nanozyme.

A core-shell-structured Cu2 O@Mn3 Cu3 O8 (CMCO) nanozyme is constructed to serve as a tumor microenvironment (TME)-activated copper ionophore to achieve safe and efficient cuproptosis. The Mn3 Cu3 O8 shell not only prevents exposure of normal tissues to the Cu2 O core to reduce systemic toxicity but also exhibits enhanced enzyme-mimicking activity owing to the better band continuity near the Fermi surface. The glutathione oxidase (GSHOx)-like activity of CMCO depletes glutathione (GSH), which diminishes the ability to chelate Cu ions, thereby exerting Cu toxicity and inducing cuproptosis in cancer cells. The catalase (CAT)-like activity catalyzes the overexpressed H2 O2 in the TME, thereby generating O2 in the tricarboxylic acid (TCA) cycle to enhance cuproptosis. More importantly, the Fenton-like reaction based on the release of Mn ions and the inactivation of glutathione peroxidase 4 induced by the elimination of GSH results in ferroptosis, accompanied by the accumulation of lipid peroxidation and reactive oxygen species that can cleave stress-induced heat shock proteins to compromise their protective capacity of cancer cells and further sensitize cuproptosis. CMCO nanozymes are partially sulfurized by hydrogen sulfide in the colorectal TME, exhibiting excellent photothermal properties and enzyme-mimicking activity. The mild photothermal effect enhances the enzyme-mimicking activity of the CMCO nanozymes, thus inducing high-efficiency ferroptosis-boosted-cuproptosis.

Low-Temperature Photothermal Therapy Platform Based on Pd Nanozyme-Modified Hydrogenated TiO2.

In photothermal treatments (PTTs), normal tissues around cancerous tumors get injured by excessive heat, whereas damaged cancer cells are easily restored by stress-induced heat shock proteins (HSPs) at low temperatures. Therefore, to achieve a unique tumor microenvironment (TME), it is imperative to increase PTT efficiency and reduce normal tissue injury by adopting appropriate reactive oxygen species (ROS) and lipid peroxides (LPO) cross-linked with HSPs. In the present research, a potential strategy for mild photothermal treatments (mPTTs) was proposed by initiating localized catalytic chemical reactions in TME based on Pd nanozyme-modified hydrogenated TiO2 (H-TiO2@Pd). In vitro and in vivo evaluations demonstrated that H-TiO2@Pd had good peroxidase-like activities (POD), glutathione oxidase-like activities (GSHOx), and photodynamic properties and also satisfactory biocompatibility for 4T1 cells. Localized catalytic chemical reactions in H-TiO2@Pd significantly depleted GSH to downregulate the protein expression of GPX4 and promoted the accumulation of LPO and ROS, which consumed HSP70 or inhibited its function in 4T1 cells. Hence, the as-constructed low-temperature photothermal therapeutic platform based on Pd nanozyme-modified H-TiO2 can be a promising candidate to develop a safe and effective mPTT for cancer treatments.

Core-Shell Au@Pd Bimetallic Nanozyme Mediated Mild Photothermal Therapy through Reactive Oxygen Species-Regulating Tumor Thermoresistance.

Mild photothermal therapy (mPTT), which circumvents the limitations of conventional photothermal therapy, is emerging and exhibits remarkable potential in clinical applications. Nevertheless, mPTT is not able to efficiently eradicate tumors because its therapeutic efficacy is dramatically diminished by stress-induced heat shock proteins (HSP). Herein, a core-shell structured Au@Pd (AP) bimetallic nanozyme was fabricated for reactive oxygen species (ROS) augmentation-induced mPTT. The nanocatalytic AP nanozymes with photothermal conversion performance harbor multienzymatic (catalase, oxidase, and peroxidase) activities to induce ROS storm formation. The generated ROS could suppress the heat-defense response of tumor cells by cleaving HSP. Overall, our work highlights a ROS-regulating strategy to counteract hyperthermia-associated resistance in mPTT.

Poly(acrylic acid)-modified Fe3O4 microspheres for magnetic-targeted and pH-triggered anticancer drug delivery.

Monodisperse poly(acrylic acid)-modified Fe(3)O(4) (PAA@Fe(3)O(4)) hybrid microspheres with dual responses (magnetic field and pH) were successfully fabricated. The PAA polymer was encapsulated into the inner cavity of Fe(3)O(4) hollow spheres by a vacuum-casting route and photo-initiated polymerization. TEM images show that the samples consist of monodisperse porous spheres with a diameter around 200 nm. The Fe(3)O(4) spheres, after modification with the PAA polymer, still possess enough space to hold guest molecules. We selected doxorubicin (DOX) as a model drug to investigate the drug loading and release behavior of as-prepared composites. The release of DOX molecules was strongly dependent on the pH value due to the unique property of PAA. The HeLa cell-uptake process of DOX-loaded PAA@Fe(3)O(4) was observed by confocal laser scanning microscopy (CLSM). After being incubated with HeLa cells under magnet magnetically guided conditions, the cytotoxtic effects of DOX-loaded PAA@Fe(3)O(4) increased. These results indicate that pH-responsive magnetic PAA@Fe(3)O(4) spheres have the potential to be used as anticancer drug carriers.

Tumor-Microenvironment-Activated Reactive Oxygen Species Amplifier for Enzymatic Cascade Cancer Starvation/Chemodynamic /Immunotherapy.

At present, some progress has been made in the field of cancer theranostics based on nanocatalysts (NCs), but achieving precise theranostics in response to the specific tumor microenvironment (TME) remains a major challenge. Herein, a TME-responsive upconversion nanoparticles (UCNPs)-based smart UCNPs@Cu-Cys-GOx (UCCG) nanosystem is engineered, which combines natural enzymes and nanozymes so as to amplify reactive oxygen species (ROS) generation in situ for cancer starvation/chemodynamic/immunotherapy. One of the biggest merits of this material is that it can be preserved inert (off) in normal tissues, and only in the TME can it be specifically activated (on) through a series of enzymatic cascades to boost ROS production via a strategy of open source (H2 O2 self-supplying ability) and reduce expenditure (glutathione (GSH) consuming ability). More importantly, the enhanced oxidative stress by UCCG NCs reverses the immunosuppressive TME, and facilitates antitumor immune responses. Meanwhile, the starvation/chemodynamic synergistic therapy triggered by UCCG combined with PD-L1 antibody effectively inhibits the growth of primary tumors and cancer metastasis. In addition, the UCNPs in UCCG present upconversion luminescence enhancement, which can be exploited to visualize the reinforced ROS generation in real time. Collectively, this work provides an original method for the devising and exploitation of UCNPs-based catalytic immunotherapy.

Surface-Functionalized NdVO4:Gd3+ Nanoplates as Active Agents for Near-Infrared-Light-Triggered and Multimodal-Imaging-Guided Photothermal Therapy.

Development of nanotheranostic agents with near-infrared (NIR) absorption offers an effective tool for fighting malignant diseases. Lanthanide ion neodymium (Nd3+)-based nanomaterials, due to the maximum absorption at around 800 nm and unique optical properties, have caught great attention as potential agents for simultaneous cancer diagnosis and therapy. Herein, we employed an active nanoplatform based on gadolinium-ion-doped NdVO4 nanoplates (NdVO4:Gd3+ NPs) for multiple-imaging-assisted photothermal therapy. These NPs exhibited enhanced NIR absorption and excellent biocompatibility after being grafted with polydopamine (pDA) and bovine serum albumin (BSA) layers on their surface. Upon expose to an 808 nm laser, these resulting NPs were able to trigger hyperthermia rapidly and cause photo-destruction of cancer cells. In a xenograft tumor model, tumor growth was also significantly inhibited by these photothermal agents under NIR laser irradiation. Owing to the multicomponent nanostructures, we demonstrated these nanoagents as being novel contrast agents for in vivo magnetic resonance (MR) imaging, X-ray computed tomography (CT), photoacoustic (PA) imaging, and second biological window fluorescent imaging of tumor models. Thus, we believe that this new kind of nanotherapeutic will benefit the development of emerging nanosystems for biological imaging and cancer therapy.