Ultrasmall Nanoplatforms as Calcium‐Responsive Contrast Agents for Magnetic Resonance Imaging

The preparation of ultrasmall and rigid platforms (USRPs) that are covalently coupled to macrocycle‐based, calcium‐responsive/smart contrast agents (SCAs), and the initial in vitro and in vivo validation of the resulting nanosized probes (SCA‐USRPs) by means of magnetic resonance imaging (MRI) is reported. The synthetic procedure is robust, allowing preparation of the SCA‐USRPs on a multigram scale. The resulting platforms display the desired MRI activity—i.e., longitudinal relaxivity increases almost twice at 7 T magnetic field strength upon saturation with Ca²⁺. Cell viability is probed with the MTT assay using HEK‐293 cells, which show good tolerance for lower contrast agent concentrations over longer periods of time. On intravenous administration of SCA‐USRPs in living mice, MRI studies indicate their rapid accumulation in the renal pelvis and parenchyma. Importantly, the MRI signal increases in both kidney compartments when CaCl₂ is also administrated. Laser‐induced breakdown spectroscopy experiments confirm accumulation of SCA‐USRPs in the renal cortex. To the best of our knowledge, these are the first studies which demonstrate calcium‐sensitive MRI signal changes in vivo. Continuing contrast agent and MRI protocol optimizations should lead to wider application of these responsive probes and development of superior functional methods for monitoring calcium‐dependent physiological and pathological processes in a dynamic manner.     

Breaking the Depth Dependence by Nanotechnology‐Enhanced X‐Ray‐Excited Deep Cancer Theranostics

The advancements in nanotechnology have created multifunctional nanomaterials aimed at enhancing diagnostic accuracy and treatment efficacy for cancer. However, the ability to target deep‐seated tumors remains one of the most critical challenges for certain nanomedicine applications. To this end, X‐ray‐excited theranostic techniques provide a means of overcoming the limits of light penetration and tissue attenuation. Herein, a comprehensive overview of the recent advances in nanotechnology‐enhanced X‐ray‐excited imaging and therapeutic methodologies is presented, with an emphasis on the design of multifunctional nanomaterials for contrast‐enhanced computed tomography (CT) imaging, X‐ray‐excited optical luminescence (XEOL) imaging, and X‐ray‐excited multimodal synchronous/synergistic therapy. The latter is based on the concurrent use of radiotherapy with chemotherapy, gas therapy, photodynamic therapy, or immunotherapy. Moreover, the featured biomedical applications of X‐ray‐excited deep theranostics are discussed to highlight the advantages of X‐ray in high‐sensitivity detection and efficient elimination of malignant tumors. Finally, key issues and technical challenges associated with this deep theranostic technology are identified, with the intention of advancing its translation into the clinic.     

Advanced Nanotechnology Leading the Way to Multimodal Imaging‐Guided Precision Surgical Therapy

Surgical resection is the primary and most effective treatment for most patients with solid tumors. However, patients suffer from postoperative recurrence and metastasis. In the past years, emerging nanotechnology has led the way to minimally invasive, precision and intelligent oncological surgery after the rapid development of minimally invasive surgical technology. Advanced nanotechnology in the construction of nanomaterials (NMs) for precision imaging‐guided surgery (IGS) as well as surgery‐assisted synergistic therapy is summarized, thereby unlocking the advantages of nanotechnology in multimodal IGS‐assisted precision synergistic cancer therapy. First, mechanisms and principles of NMs to surgical targets are briefly introduced. Multimodal imaging based on molecular imaging technologies provides a practical method to achieve intraoperative visualization with high resolution and deep tissue penetration. Moreover, multifunctional NMs synergize surgery with adjuvant therapy (e.g., chemotherapy, immunotherapy, phototherapy) to eliminate residual lesions. Finally, key issues in the development of ideal theranostic NMs associated with surgical applications and challenges of clinical transformation are discussed to push forward further development of NMs for multimodal IGS‐assisted precision synergistic cancer therapy.     

Fucoidan-Based Theranostic Nanogel for Enhancing Imaging and Photodynamic Therapy of Cancer

In this study, a fucoidan-based theranostic nanogel(CFN-gel) consisting of a fucoidan backbone, redox-responsive cleavable linker and photosensitizer is developed to achieve acti-vatable near-infrared fluorescence imaging of tumor sites and an enhanced photodynamic therapy(PDT) to induce the com-plete death of cancer cells. A CFN-gel has nanomolar a nity for P-selectin, which is overexpressed on the surface of tumor neovascular endothelial cells as well as many other cancer cells. Therefore, a CFN-gel can enhance tumor accumulation through P-selectin targeting and the enhanced permeation and retention e ect. Moreover, a CFN-gel is non-fluorescent and non-phototoxic upon its systemic administration due to the aggregation-induced self-quenching in its fluorescence and singlet oxygen generation. After internalization into cancer cells and tumor neovascular endothelial cells, its photoactivity is recovered in response to the intracellular redox potential, thereby enabling selective near-infrared fluorescence imaging and an enhanced PDT of tumors. Since a CFN-gel also shows nanomolar a nity for the vascular endothelial growth factor, it also provides a significant anti-tumor e ect in the absence of light treatment in vivo. Our study indicates that a fucoidan-based theranostic nanogel is a new theranostic material for imaging and treating cancer with high e cacy and specificity.     

Nanoparticle‐Enabled,Image‐Guided Treatment Planning of Target Specific RNAi Therapeutics in an Orthotopic Prostate Cancer Model

The abilities to deliver siRNA to its intended action site and assess the delivery efficiency are challenges for current RNAi therapy, where effective siRNA delivery will join force with patient genetic profiling to achieve optimal treatment outcome. Imaging could become a critical enabler to maximize RNAi efficacy in the context of tracking siRNA delivery, rational dosimetry and treatment planning. Several imaging modalities have been used to visualize nanoparticle‐based siRNA delivery but rarely did they guide treatment planning. We report a multimodal theranostic lipid‐nanoparticle, HPPS(NIR)‐chol‐siRNA, which has a near‐infrared (NIR) fluorescent core, enveloped by phospholipid monolayer, intercalated with siRNA payloads, and constrained by apoA‐I mimetic peptides to give ultra‐small particle size (<30 nm). Using fluorescence imaging, we demonstrated its cytosolic delivery capability for both NIR‐core and dye‐labeled siRNAs and its structural integrity in mice through intravenous administration, validating the usefulness of NIR‐core as imaging surrogate for non‐labeled therapeutic siRNAs. Next, we validated the targeting specificity of HPPS(NIR)‐chol‐siRNA to orthotopic tumor using sequential four‐steps (in vivo, in situ, ex vivo and frozen‐tissue) fluorescence imaging. The image co‐registration of computed tomography and fluorescence molecular tomography enabled non‐invasive assessment and treatment planning of siRNA delivery into the orthotopic tumor, achieving efficacious RNAi therapy.     

Biofunctionalized,Phosphonate‐Grafted,Ultrasmall Iron Oxide Nanoparticles for Combined Targeted Cancer Therapy and Multimodal Imaging

A novel, inexpensive biofunctionalization approach is adopted to develop a multimodal and theranostic nanoagent, which combines cancer‐targeted magnetic resonance/optical imaging and pH‐sensitive drug release into one system. This multifunctional nanosystem, based on an ultrasmall superparamagnetic iron oxide (USPIO) nanocore, is modified with a hydrophilic, biocompatible, and biodegradable coating of N‐phosphonomethyl iminodiacetic acid (PMIDA). Using appropriate spacers, functional molecules, such as rhodamine B isothiocyanate, folic acid, and methotrexate, are coupled to the amine‐derivatized USPIO–PMIDA support with the aim of endowing simultaneous targeting, imaging, and intracellular drug‐delivering capability. For the first time, phosphonic acid chemistry is successfully exploited to develop a stealth, multifunctional nanoprobe that can selectively target, detect, and kill cancer cells overexpressing the folate receptor, while allowing real‐time monitoring of tumor response to drug treatment through dual‐modal fluorescence and magnetic resonance imaging.     

Facile and Scalable Synthesis of Novel Spherical Au Nanocluster Assemblies@Polyacrylic Acid/Calcium Phosphate Nanoparticles for Dual‐Modal Imaging‐Guided Cancer Chemotherapy

Engineering novel theranostic agents with both imaging and therapeutic functions have profound impact on molecular diagnostics, imaging, and therapeutics. In this paper, we develop for the first time a simple, scalable, and reproducible route to synthesize novel multifunctional spherical Au nanoclusters assemblies encapsulated by a polyacylic acid (PAA)/calcium phosphate (CaP) shell with aggregation enhanced fluorescence property (designated as AuNCs‐A@PAA/CaP). Furthermore, the resulting AuNCs‐A@PAA/CaP nanoparticles (NPs) possess a high payload of doxorubicin as synergetic pH‐sensitive drug delivery vehicles to employ for dual‐modal computed tomography (CT) and fluorescence imaging‐guided liver cancer chemotherapy in vivo. The results reveal that AuNCs‐A@PAA/CaP NPs not only provide excellent bimodal CT and fluorescence contrast imaging but also present efficient tumor ablation under the guidance of CT and fluorescence imaging, to achieve excellent chemotherapeutic efficacy to the hepatocarcinoma cell line (H‐22) bearing mice through intravenous injection. Comprehensive blood tests and careful histological examinations reveal no apparent toxicity of AuNCs‐A@PAA/CaP NPs. Our work highlights the great promise of AuNCs‐A@PAA/CaP NPs for guiding and monitoring the chemotherapeutic process using simultaneous dual‐modality CT and fluorescence imaging through a single theranostic agent.     

Drug/Dye‐Loaded,Multifunctional Iron Oxide Nanoparticles for Combined Targeted Cancer Therapy and Dual Optical/Magnetic Resonance Imaging

A biocompatible, multimodal, and theranostic functional iron oxide nanoparticle is synthesized using a novel water‐based method and exerts excellent properties for targeted cancer therapy, and optical and magnetic resonance imaging. For the first time, a facile, modified solvent diffusion method is used for the co‐encapsulation of both an anticancer drug and near‐infrared dyes. The resulting folate‐derivatized theranostics nanoparticles could allow for targeted optical/magnetic resonance imaging and targeted killing of folate‐expressing cancer cells.     

The Nanoassembly of an Intrinsically Cytotoxic Near‐Infrared Dye for Multifunctionally Synergistic Theranostics

The combination of diagnostic and therapeutic functions in a single theranostic nanoagent generally requires the integration of multi‐ingredients. Herein, a cytotoxic near‐infrared (NIR) dye (IR‐797) and its nanoassembly are reported for multifunctional cancer theranostics. The hydrophobic IR‐797 molecules are self‐assembled into nanoparticles, which are further modified with an amphiphilic polymer (C18PMH‐PEG5000) on the surface. The prepared PEG‐IR‐797 nanoparticles (PEG‐IR‐797 NPs) possess inherent cytotoxicity from the IR‐797 dye and work as a chemotherapeutic drug which induces apoptosis of cancer cells. The IR‐797 NPs are found to have an ultrahigh mass extinction coefficient (444.3 L g^?1 cm^?1 at 797 nm and 385.9 L g^?1 cm^?1 at 808 nm) beyond all reported organic nanomaterials (<40 L g^?1 cm^?1) for superior photothermal therapy (PTT). In addition, IR‐797 shows some aggregation‐induced‐emission (AIE) properties. Combining the merits of good NIR absorption, high photothermal energy conversion efficiency, and AIE, makes the PEG‐IR‐797 NPs useful for multimodal NIR AIE fluorescence, photoacoustic, and thermal imaging‐guided therapy. The research exhibits the possibility of using a single ingredient and entity to perform multimodal NIR fluorescence, photoacoustic, and thermal imaging‐guided chemo‐/photothermal combination therapy, which may trigger wide interest from the fields of nanomedicine and medicinal chemistry to explore multifunctional theranostic organic molecules.     

A Self‐Assembled Biocompatible Nanoplatform for Multimodal MR/Fluorescence Imaging Assisted Photothermal Therapy and Prognosis Analysis

The need for better imaging assisted cancer therapy calls for new biocompatible agents with excellent imaging and therapeutic capabilities. This study successfully fabricates albumin‐cooperated human serum albumin (HSA)‐GGD‐ICG nanoparticles (NPs), which are comprised of a magnetic resonance (MR) contrast agent, glycyrrhetinic‐acid‐modified gadolinium (III)‐1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetate (GGD), and a fluorescence (FL) dye, indocyanine green (ICG), for multimodal MR/FL imaging assisted cancer therapy. These HSA‐GGD‐ICG NPs with excellent biocompatibility are stable under physiological conditions, and exhibit enhanced T₁ contrast capability and improved fluorescence imaging capacity. In vitro experiments reveal an apparent effect of the NPs in killing tumor cells under low laser irradiation, due to the enhanced photothermal conversion efficiency (≈85.1%). Importantly, multimodal MR/FL imaging clearly shows the in vivo behaviors and the efficiency of tumor accumulation of HSA‐GGD‐ICG NPs, as confirmed by a pharmacokinetic study. With the guidance of multimodal imaging, photothermal therapy is subsequently conducted, which demonstrates again high photothermal conversion capability for eliminating tumors without relapse. Notably, real‐time monitoring of tumor ablation for prognosis and therapy evaluation is also achieved by MR imaging. This strategy of constructing nanoplatforms through albumin‐mediated methods is both convenient and efficient, which would enlighten the design of multimodal imaging assisted cancer therapy for potential clinical translation.     

A Versatile Theranostic Nanoemulsion for Architecture‐Dependent Multimodal Imaging and Dually Augmented Photodynamic Therapy

To design a clinically translatable nanomedicine for photodynamic theranostics, the ingredients should be carefully considered. A high content of nanocarriers may cause extra toxicity in metabolism, and multiple theranostic agents would complicate the preparation process. These issues would be of less concern if the nanocarrier itself has most of the theranostic functions. In this work, a poly(ethylene glycol)‐boron dipyrromethene amphiphile (PEG‐F₅₄‐BODIPY) with 54 fluorine‐19 (¹⁹F) is synthesized and employed to emulsify perfluorohexane (PFH) into a theranostic nanoemulsion (PFH@PEG‐F₅₄‐BODIPY). The as‐prepared PFH@PEG‐F₅₄‐BODIPY can perform architecture‐dependent fluorescence/photoacoustic/¹⁹F magnetic resonance multimodal imaging, providing more information about the in vivo structure evolution of nanomedicine. Importantly, this nanoemulsion significantly enhances the therapeutic effect of BODIPY through both the high oxygen dissolving capability and less self‐quenching of BODIPY molecules. More interestingly, PFH@PEG‐F₅₄‐BODIPY shows high level of tumor accumulation and long tumor retention time, allowing a repeated light irradiation after a single‐dose intravenous injection. The “all‐in‐one” photodynamic theranostic nanoemulsion has simple composition, remarkable theranostic efficacy, and novel treatment pattern, and thus presents an intriguing avenue to developing clinically translatable theranostic agents.     

A Light‐Activated Theranostic Nanoagent for Targeted Macrophage Ablation in Inflammatory Atherosclerosis

The synthesis and utility of a multimodal theranostic nanoagent based upon magnetofluorescent nanoparticles for the treatment of inflammatory atherosclerosis is described. These particles are modified with near‐infrared fluorophores and light‐activated therapeutic moieties, which allow for the optical determination of agent localization and phototoxic activation at spectrally distinct wavelengths. The resulting agent is readily taken up by murine macrophages in vitro and is highly phototoxic, with an LD₅₀ of 430 pM . Intravenous administration results in the localization of the nanoagent within macrophage‐rich atherosclerotic lesions that can be imaged by intravital fluorescence microscopy. Irradiation of the atheroma with 650 nm light activates the therapeutic component and results in eradication of inflammatory macrophages, which may induce lesion stabilization. Importantly, these agents display limited skin photosensitivity, are highly efficacious, and provide an integrated imaging and therapeutic nanoplatform for atherosclerosis.     

Dual‐Stimuli Responsive Nanotheranostics for Multimodal Imaging Guided Trimodal Synergistic Therapy

Multimodal imaging guided synergistic therapy promises more accurate diagnosis than any single imaging modality, and higher therapeutic efficiency than any single one or their simple “mechanical” combination. Herein, we report a dual‐stimuli responsive nanotheranostic based on a hierarchical nanoplatform, composed of mesoporous silica‐coated gold nanorods (GNR@SiO2), Indocyanine Green (ICG), and 5‐fluorouracil (5‐FU), for in vivo multimodal imaging guided synergistic therapy. The 5‐FU loaded ICG‐conjugated silica‐coated gold nanorods (GNR@SiO2‐5‐FU‐ICG) was able to response specifically to the two stimuli of pH change and near‐infrared (NIR) light irradiation. Both the NIR light irradiation and acidic environment accelerated the 5‐FU release. Meanwhile, the heat generation and singlet oxygen production can be induced by GNR@SiO2‐5‐FU‐ICG upon light irradiation. Most intriguingly, the nanoplatform also promises multimodal imaging such as two‐photon luminescence, fluorescence, photoacoustic, photothermal imaging, as well as trimodal synergistic therapy such as photothermal therapy (PTT), photodynamic therapy (PDT), and chemotherapy. The cancer theranostic capability of GNR@SiO2‐5‐FU‐ICG was evaluated both in vitro and in vivo. The trimodal synergistic therapy with the guidance of multimodal imaging exhibited remarkably enhanced treatment efficacy. This concept of a hierarchical nanoplatform integrates multiple diagnostic/therapeutic modalities into one platform, which can potentially be applied as personalized nanomedicine with drug delivery, diagnosis, and treatment.     

Tumor‐Targeting Multifunctional Rattle‐Type Theranostic Nanoparticles for MRI/NIRF Bimodal Imaging and Delivery of Hydrophobic Drugs

The development of theranostic systems capable of diagnosis, therapy, and target specificity is considerably significant for accomplishing personalized medicine. Here, a multifunctional rattle‐type nanoparticle (MRTN) as an effective biological bimodal imaging and tumor‐targeting delivery system is fabricated, and an enhanced loading ability of hydrophobic anticancer drug (paclitaxel) is also realized. The rattle structure with hydrophobic Fe₃O₄ as the inner core and mesoporous silica as the shell is obtained by one‐step templates removal process, and the size of interstitial hollow space can be easily adjusted. The Fe₃O₄ core with hydrophobic poly(tert‐butyl acrylate) (PTBA) chains on the surface is not only used as a magnetic resonance imaging (MRI) agent, but contributes to improving hydrophobic drug loading amount. Transferrin (Tf) and a near‐infrared fluorescent dye (Cy 7) are successfully modified on the surface of the nanorattle to increase the ability of near‐infrared fluorescence (NIRF) imaging and tumor‐targeting specificity. In vivo studies show the selective accumulation of MRTN in tumor tissues by Tf‐receptor‐mediated endocytosis. More importantly, paclitaxel‐loaded MRTN shows sustained release character and higher cytotoxicity than the free paclitaxel. This theranostic nanoparticle as an effective MRI/NIRF bimodal imaging probe and drug delivery system shows great potential in cancer diagnosis and therapy.     

Development of Novel Tumor‐Targeted Theranostic Nanoparticles Activated by Membrane‐Type Matrix Metalloproteinases for Combined Cancer Magnetic Resonance Imaging and Therapy

A major drawback with current cancer therapy is the prevalence of unrequired dose‐limiting toxicity to non‐cancerous tissues and organs, which is further compounded by a limited ability to rapidly and easily monitor drug delivery, pharmacodynamics and therapeutic response. In this report, the design and characterization of novel multifunctional “theranostic” nanoparticles (TNPs) is described for enzyme‐specific drug activation at tumor sites and simultaneous in vivo magnetic resonance imaging (MRI) of drug delivery. TNPs are synthesized by conjugation of FDA‐approved iron oxide nanoparticles ferumoxytol to an MMP‐activatable peptide conjugate of azademethylcolchicine (ICT), creating CLIO‐ICTs (TNPs). Significant cell death is observed in TNP‐treated MMP‐14 positive MMTV‐PyMT breast cancer cells in vitro, but not MMP‐14 negative fibroblasts or cells treated with ferumoxytol alone. Intravenous administration of TNPs to MMTV‐PyMT tumor‐bearing mice and subsequent MRI demonstrates significant tumor selective accumulation of the TNP, an observation confirmed by histopathology. Treatment with CLIO‐ICTs induces a significant antitumor effect and tumor necrosis, a response not observed with ferumoxytol. Furthermore, no toxicity or cell death is observed in normal tissues following treatment with CLIO‐ICTs, ICT, or ferumoxytol. These findings demonstrate proof of concept for a new nanotemplate that integrates tumor specificity, drug delivery and in vivo imaging into a single TNP entity through attachment of enzyme‐activated prodrugs onto magnetic nanoparticles. This novel approach holds the potential to significantly improve targeted cancer therapies, and ultimately enable personalized therapy regimens.     

Structure‐Guided Design and Synthesis of a Mitochondria‐Targeting Near‐Infrared Fluorophore with Multimodal Therapeutic Activities

An urgent challenge for imaging‐guided disease‐targeted multimodal therapy is to develop the appropriate multifunctional agents to meet the requirements for potential applications. Here, a rigid cyclohexenyl substitution in the middle of a polymethine linker and two asymmetrical amphipathic N‐alkyl side chains to indocyanine green (ICG) (the only FDA‐approved NIR contrast agent) are introduced, and a new analog, IR‐DBI, is developed with simultaneous cancer‐cell mitochondrial targeting, NIR imaging, and chemo‐/PDT/PTT/multimodal therapeutic activities. The asymmetrical and amphipathic structural modification renders IR‐DBI a close binding to albumin protein site II to form a drug–protein complex and primarily facilitates its preferential accumulation at tumor sites via the enhanced permeability and retention (EPR) effect. The released IR‐DBI dye is further actively taken up by cancer cells through organic‐anion‐transporting polypeptide transporters, and the lipophilic cationic property leads to its selective accumulation in the mitochondria of cancer cells. Finally, based on the high albumin‐binding affinity, IR‐DBI is modified into human serum albumin (HSA) via self‐assembly to produce a nanosized complex, which exhibits significant improvement in the cancer targeting and multimodal cancer treatment with better biocompatibility. This finding may present a practicable strategy to develop small‐molecule‐based cancer theranostic agents for simultaneous cancer diagnostics and therapeutics.     

Single‐Photomolecular Nanotheranostics for Synergetic Near‐Infrared Fluorescence and Photoacoustic Imaging‐Guided Highly Effective Photothermal Ablation

Multi‐modality imaging‐guided cancer therapy is considered as a powerful theranostic platform enabling simultaneous precise diagnosis and treatment of cancer. However, recently reported multifunctional systems with multiple components and sophisticate structures remain major obstacles for further clinical translation. In this work, a single‐photomolecular theranostic nanoplatform is fabricated via a facile nanoprecipitation strategy. By encapsulating a semiconductor oligomer (IT‐S) into an amphiphilic lipid, water‐dispersible IT‐S nanoparticles (IT‐S NPs) are prepared. The obtained IT‐S NPs have a very simple construction and possess ultra‐stable near‐infrared (NIR) fluorescence (FL)/photoacoustic (PA) dual‐modal imaging and high photothermal conversion efficiency of 72.3%. Accurate spatiotemporal distribution profiles of IT‐S NPs are successfully visualized by NIR FL/PA dual‐modal imaging. With the comprehensive in vivo imaging information provided by IT‐S NPs, tumor photothermal ablation is readily realized under precise manipulation of laser irradiation, which greatly improves the therapeutic efficacy without any obvious side effects. Therefore, the IT‐S NPs allow high tumor therapeutic efficacy under the precise guidance of FL/PA imaging techniques and thus hold great potential as an effective theranostic platform for future clinical applications.     

Activatable Semiconducting Theranostics: Simultaneous Generation and Ratiometric Photoacoustic Imaging of Reactive Oxygen Species In Vivo

Enhancing the generation of reactive oxygen species (ROS) is an effective anticancer strategy. However, it is a great challenge to control the production and to image ROS in vivo, both of which are vital for improving the efficacy and accuracy of cancer therapy. Herein, an activatable semiconducting theranostic nanoparticle (NP) platform is developed that can simultaneously enhance ROS generation while self‐monitoring its levels through ratiometric photoacoustic (PA) imaging. The NP platform can further guide in vivo therapeutic effect in tumors. The theranostic NP platform is composed of: (i) cisplatin prodrug and ferric ion catalyst for ROS generation, a part of combination cancer therapy; and (ii) a ratiometric PA imaging nanoprobe consisting of inert semiconducting perylene‐diimide (PDI) and ROS activatable near‐infrared dye (IR790s), used in ratiometric PA imaging of ROS during cancer treatment. Ratiometric PA signals are measured at two near‐infrared excitation wavelengths: 680 and 790 nm for PDI and IR790s, respectively. The measurements show highly accurate visualization of ^?OH generation in vivo. This novel ROS responsive organic theranostic NP allows not only synergistic cancer chemotherapy but also real‐time monitoring of the therapeutic effect through ratiometric PA imaging.     

Color‐Convertible,Unimolecular, Micelle‐Based,Activatable Fluorescent Probe for Tumor‐Specific Detection and Imaging In Vitro and In Vivo

Recent years have witnessed significant progress in molecular probes for cancer diagnosis. However, the conventional molecular probes are designed to be “always‐on” by attachment of tumor‐targeting ligands, which limits their abilities to diagnose tumors universally due to the variations of targeting efficiency and complex environment in different cancers. Here, it is proposed that a color‐convertible, activatable probe is responding to a universal tumor microenvironment for tumor‐specific diagnosis without targeting ligands. Based on the significant hallmark of up‐regulated hydrogen peroxide (H₂O₂) in various tumors, a novel unimolecular micelle constructed by boronate coupling of a hydrophobic hyperbranched poly(fluorene‐co‐2,1,3‐benzothiadiazole) core and many hydrophilic poly(ethylene glycol) arms is built as an H₂O₂‐activatable fluorescent nanoprobe to delineate tumors from normal tissues through an aggregation‐enhanced fluorescence resonance energy transfer strategy. This color‐convertible, activatable nanoprobe is obviously blue‐fluorescent in various normal cells, but becomes highly green‐emissive in various cancer cells. After intravenous injection to tumor‐bearing mice, green fluorescent signals are only detected in tumor tissue. These observations are further confirmed by direct in vivo and ex vivo tumor imaging and immunofluorescence analysis. Such a facile and simple methodology without targeting ligands for tumor‐specific detection and imaging is worthwhile to further development.     

Multimodal imaging guided photothermal therapy using functionalized graphene nanosheets anchored with magnetic nanoparticles

In this work, a nanoscale reduced graphene oxide-iron oxide nanoparticle (RGO-IONP) complex is noncovalently functionalized with polyethylene glycol (PEG), obtaining a RGO-IONP-PEG nanocomposite with excellent physiological stability, strong NIR optical absorbance, and superparamagnetic properties. Using this theranostic nanoprobe, in-vivo triple modal fluorescence, photoacoustic, and magnetic resonance imaging are carried out, uncovering high passive tumor targeting, which is further used for effective photothermal ablation of tumors in mice.