Precise Deciphering of Brain Vasculatures and Microscopic Tumors with Dual NIR‐II Fluorescence and Photoacoustic Imaging

Diagnostics of cerebrovascular structures and microscopic tumors with intact blood–brain barrier (BBB) significantly contributes to timely treatment of patients bearing neurological diseases. Dual NIR‐II fluorescence and photoacoustic imaging (PAI) is expected to offer powerful strength, including good spatiotemporal resolution, deep penetration, and large signal‐to‐background ratio (SBR) for precise brain diagnostics. Herein, biocompatible and photostable conjugated polymer nanoparticles (CP NPs) are reported for dual‐modality brain imaging in the NIR‐II window. Uniform CP NPs with a size of 50 nm are fabricated from microfluidics devices, which show an emission peak at 1156 nm with a large absorptivity of 35.2 L g^?1 cm^?1 at 1000 nm. The NIR‐II fluorescence imaging resolves hemodynamics and cerebral vasculatures with a spatial resolution of 23 µm at a depth of 600 µm. The NIR‐II PAI enables successful noninvasive mapping of deep microscopic brain tumors (<2 mm at a depth of 2.4 mm beneath dense skull and scalp) with an SBR of 7.2 after focused ultrasound‐induced BBB opening. This study demonstrates that CP NPs are promising contrast agents for brain diagnostics.     

Bright Aggregation‐Induced‐Emission Dots for Targeted Synergetic NIR‐II Fluorescence and NIR‐I Photoacoustic Imaging of Orthotopic Brain Tumors

Precise diagnostics are of significant importance to the optimal treatment outcomes of patients bearing brain tumors. NIR‐II fluorescence imaging holds great promise for brain‐tumor diagnostics with deep penetration and high sensitivity. This requires the development of organic NIR‐II fluorescent agents with high quantum yield (QY), which is difficult to achieve. Herein, the design and synthesis of a new NIR‐II fluorescent molecule with aggregation‐induced‐emission (AIE) characteristics is reported for orthotopic brain‐tumor imaging. Encapsulation of the molecule in a polymer matrix yields AIE dots showing a very high QY of 6.2% with a large absorptivity of 10.2 L g^?1 cm^?1 at 740 nm and an emission maximum near 1000 nm. Further decoration of the AIE dots with c‐RGD yields targeted AIE dots, which afford specific and selective tumor uptake, with a high signal/background ratio of 4.4 and resolution up to 38 µm. The large NIR absorptivity of the AIE dots facilitates NIR‐I photoacoustic imaging with intrinsically deeper penetration than NIR‐II fluorescence imaging and, more importantly, precise tumor‐depth detection through intact scalp and skull. This research demonstrates the promise of NIR‐II AIE molecules and their dots in dual NIR‐II fluorescence and NIR‐I photoacoustic imaging for precise brain cancer diagnostics.     

Metabolizable Semiconducting Polymer Nanoparticles for Second Near‐Infrared Photoacoustic Imaging

Photoacoustic (PA) imaging in the second near‐infrared (NIR‐II) window (1000–1700 nm) holds great promise for deep‐tissue diagnosis due to the reduced light scattering and minimized tissue absorption; however, exploration of such a noninvasive imaging technique is greatly constrained by the lack of biodegradable NIR‐II absorbing agents. Herein, the first series of metabolizable NIR‐II PA agents are reported based on semiconducting polymer nanoparticles (SPNs). Such completely organic nanoagents consist of π‐conjugated yet oxidizable optical polymer as PA generator and hydrolyzable amphiphilic polymer as particle matrix to provide water solubility. The obtained SPNs are readily degraded by myeloperoxidase and lipase abundant in phagocytes, transforming from nonfluorescent nanoparticles (30 nm) into NIR fluorescent ultrasmall metabolites (≈1 nm). As such, these nanoagents can be effectively cleared out via both hepatobiliary and renal excretions after systematic administration, leaving no toxicity to living mice. Particularly these nanoagents possess high photothermal conversion efficiencies and emit bright PA signals at 1064 nm, enabling sensitive NIR‐II PA imaging of both subcutaneous tumor and deep brain vasculature through intact skull in living animals at a low systematic dosage. This study thus provides a generalized molecular design toward organic metabolizable semiconducting materials for biophotonic applications in NIR‐II window.     

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.     

Ultrastable Near‐Infrared Conjugated‐Polymer Nanoparticles for Dually Photoactive Tumor Inhibition

It is highly desired that satisfactory photoactive agents with ideal photophysical characteristics are explored for potent cancer phototherapeutics. Herein, bifunctional nanoparticles of low‐bandgap donor–acceptor (D–A)‐type conjugated‐polymer nanoparticles (CP‐NPs) are developed to afford a highly efficient singlet‐to‐triplet transition and photothermal conversion for near‐infrared (NIR) light‐induced photodynamic (PDT)/photothermal (PTT) treatment. CP‐NPs display remarkable NIR absorption with the peak at 782 nm, and perfect resistance to photobleaching. Photoexcited CP‐NPs undergo singlet‐to‐triplet intersystem crossing through charge transfer in the excited D–A system and simultaneous nonradiative decay from the electron‐deficient electron acceptor isoindigo derivative under single‐wavelength NIR light irradiation, leading to distinct singlet oxygen quantum yield and high photothermal conversion efficiency. Moreover, the CP‐NPs display effective cellular uptake and cytoplasmic translocation from lysosomes, as well as effective tumor accumulation, thus promoting severe light‐triggered damage caused by favorable reactive oxygen species (ROS) generation and potent hyperthermia. Thus, CP‐NPs achieve photoactive cell damage through their photoconversion ability for synergistic PDT/PTT treatment with tumor ablation. The proof‐of‐concept design of D–A‐type conjugated‐polymer nanoparticles with ideal photophysical characteristics provides a general approach to afford potent photoactive cancer therapy.     

Flexible Photothermal Assemblies with Tunable Gold Patterns for Improved Imaging‐Guided Synergistic Therapy

Self‐assembly of gold nanoparticles demonstrates a promising approach to realize enhanced photoacoustic imaging (PAI) and photothermal therapy (PTT) for accurate diagnosis and efficient cancer therapy. Herein, unique photothermal assemblies with tunable patterns of gold nanoparticles (including arcs, rings, ribbons, and vesicles) on poly(lactic‐co‐glycolic acid) (PLGA) spheres are constructed taking advantage of emulsion‐confined and polymer‐directed self‐assembly strategies. The influencing factors and formation mechanism to produce the assemblies are investigated in details. Both the emulsion structure and migration behaviors of amphiphilic block copolymer tethered gold nanoparticles are found to contribute to the formation of versatile photothermal assemblies. Hyaluronic acid‐modified R‐PLGA‐Au (RPA) exhibits outstanding photothermal performances under NIR laser irradiation, which is induced by strong plasmonic coupling between adjacent gold nanoparticles. It is interesting that secondary assembly of RPA can be triggered by NIR laser irradiation. Prolonged residence time in tumors is achieved after RPA assemblies are fused into superstructures with larger sizes, realizing real‐time monitoring of the therapeutic processes via PAI with enhanced photoacoustic signals. Notably, synergistic effect resulting from PTT‐enhanced chemotherapy is realized to demonstrate high antitumor performance. This work provides a facile strategy to construct flexible photothermal assemblies with favorable properties for imaging‐guided synergistic therapy.     

A Hollow‐Structured CuS@Cu2S@Au Nanohybrid: Synergistically Enhanced Photothermal Efficiency and Photoswitchable Targeting Effect for Cancer Theranostics

It is of great importance in drug delivery to fabricate multifunctional nanocarriers with intelligent targeting properties, for cancer diagnosis and therapy. Herein, hollow‐structured CuS@Cu₂S@Au nanoshell/satellite nanoparticles are designed and synthesized for enhanced photothermal therapy and photoswitchable targeting theranostics. The remarkably improved photothermal conversion efficiency of CuS@Cu₂S@Au under 808 nm near‐infrared (NIR) laser irradiation can be explained by the reduced bandgap and more circuit paths for electron transitions for CuS and Cu₂S modified with Au nanoparticles, as calculated by the Vienna ab initio simulation package, based on density functional theory. By modification of thermal‐isomerization RGD targeting molecules and thermally sensitive copolymer on the surface of nanoparticles, the transition of the shielded/unshielded mode of RGD (Arg‐Gly‐Asp) targeting molecules and shrinking of the thermally sensitive polymer by NIR photoactivation can realize a photoswitchable targeting effect. After loading an anticancer drug doxorubicin in the cavity of CuS@Cu₂S@Au, the antitumor therapy efficacy is greatly enhanced by combining chemo‐ and photothermal therapy. The reported nanohybrid can also act as a photoacoustic imaging agent and an NIR thermal imaging agent for real‐time imaging, which provides a versatile platform for multifunctional theranostics and stimuli‐responsive targeted cancer therapy.     

J‐Aggregates of Organic Dye Molecules Complexed with Iron Oxide Nanoparticles for Imaging‐Guided Photothermal Therapy Under 915‐nm Light

Recently, the development of nano‐theranostic agents aiming at imaging guided therapy has received great attention. In this work, a near‐infrared (NIR) heptamethine indocyanine dye, IR825, in the presence of cationic polymer, polyallylamine hydrochloride (PAH), forms J‐aggregates with red‐shifted and significantly enhanced absorbance. After further complexing with ultra‐small iron oxide nanoparticles (IONPs) and the followed functionalization with polyethylene glycol (PEG), the obtained IR825@PAH‐IONP‐PEG composite nanoparticles are highly stable in different physiological media. With a sharp absorbance peak, IR825@PAH‐IONP‐PEG can serve as an effective photothermal agent under laser irradiation at 915 nm, which appears to be optimal in photothermal therapy application considering its improved tissue penetration compared with 808‐nm light and much lower water heating in comparison to 980‐nm light. As revealed by magnetic resonance (MR) imaging, those nanoparticles after intravenous injection exhibit high tumor accumulation, which is then harnessed for in vivo photothermal ablation of tumors, achieving excellent therapeutic efficacy in a mouse tumor model. This study demonstrates for the first time that J‐aggregates of organic dye molecules are an interesting class of photothermal material, which when combined with other imageable nanoprobes could serve as a theranostic agent for imaging‐guided photothermal therapy of cancer.     

Polyaniline Nanovesicles for Photoacoustic Imaging‐Guided Photothermal‐Chemo Synergistic Therapy in the Second Near‐Infrared Window

Photoacoustic imaging‐guided photothermal therapy in the second near‐infrared (NIR‐II) window shows promise for clinical deep‐penetrating tumor phototheranostics. However, ideal photothermal agents in the NIR‐II window are still rare. Here, the emeraldine salt of polyaniline (PANI‐ES), especially synthesized by a one‐pot enzymatic reaction on sodium bis(2‐ethylhexyl) sulfosuccinate (AOT) vesicle surface (PANI‐ES@AOT, λ_max ≈ 1000 nm), exhibits excellent dispersion in physiological environment and remarkable photothermal ability at pH 6.5 (photothermal conversion efficiency of 43.9%). As a consequence of the enhanced permeability and retention effect of tumors and the doping‐induced photothermal effect of PANI‐ES@AOT, this pH‐sensitive NIR‐II photothermal agent allows tumor acidity phototheranostics with minimized pseudosignal readout and subdued normal tissue damage. Moreover, the enhanced fluidity of vesicle membrane triggered by heating is beneficial for drug release and allows precise synergistic therapy for an improved therapeutic effect. This study highlights the potential of template‐oriented (or interface‐confined) enzymatic polymerization reactions for the construction of conjugated polymers with desired biomedical applications.     

Double‐Targeting Explosible Nanofirework for Tumor Ignition to Guide Tumor‐Depth Photothermal Therapy

This study reports a double‐targeting “nanofirework” for tumor‐ignited imaging to guide effective tumor‐depth photothermal therapy (PTT). Typically, ≈30 nm upconversion nanoparticles (UCNP) are enveloped with a hybrid corona composed of ≈4 nm CuS tethered hyaluronic acid (CuS‐HA). The HA corona provides active tumor‐targeted functionality together with excellent stability and improved biocompatibility. The dimension of UCNP@CuS‐HA is specifically set within the optimal size window for passive tumor‐targeting effect, demonstrating significant contributions to both the in vivo prolonged circulation duration and the enhanced size‐dependent tumor accumulation compared with ultrasmall CuS nanoparticles. The tumors featuring hyaluronidase (HAase) overexpression could induce the escape of CuS away from UCNP@CuS‐HA due to HAase‐catalyzed HA degradation, in turn activating the recovery of initially CuS‐quenched luminescence of UCNP and also driving the tumor‐depth infiltration of ultrasmall CuS for effective PTT. This in vivo transition has proven to be highly dependent on tumor occurrence like a tumor‐ignited explosible firework. Together with the double‐targeting functionality, the pathology‐selective tumor ignition permits precise tumor detection and imaging‐guided spatiotemporal control over PTT operation, leading to complete tumor ablation under near infrared (NIR) irradiation. This study offers a new paradigm of utilizing pathological characteristics to design nanotheranostics for precise detection and personalized therapy of tumors.     

Encapsulated Conjugated Oligomer Nanoparticles for Real‐Time Photoacoustic Sentinel Lymph Node Imaging and Targeted Photothermal Therapy

Noninvasive and nonionizing imaging of sentinel lymph nodes (SLN) is highly desirable for the detection of breast cancer metastasis through sentinel lymph node biopsy. Photoacoustic (PA) imaging is an emerging imaging technique that can serve as a suitable approach for SLN imaging. Herein, novel conjugated oligomer based nanoparticles (NPs) with strong NIR absorption, good biocompatibility, excellent PA contrast, and good photothermal conversion efficiency are reported. Real‐time PA imaging of SLN reveals high resolution of the NPs via injection from the left forepaw pad. In addition, the surface functionalized NPs can target breast cancer cells and kill them efficiently and specifically through photothermal therapy upon 808 nm laser irradiation. This work shows great potential of the nanoparticle PA contrast agent to serve as a multifunctional probe for photothermal therapy at SLNs to achieve the inhibition of cancer cell metastasis in the near future.     

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.     

High‐Resolution 3D NIR‐II Photoacoustic Imaging of Cerebral and Tumor Vasculatures Using Conjugated Polymer Nanoparticles as Contrast Agent

Exogenous contrast‐agent‐assisted NIR‐II optical‐resolution photoacoustic microscopy imaging (ORPAMI) holds promise to decipher wide‐field 3D biological structures with deep penetration, large signal‐to‐background ratio (SBR), and high maximum imaging depth to depth resolution ratio. Herein, NIR‐II conjugated polymer nanoparticle (CP NP) assisted ORPAMI is reported for pinpointing cerebral and tumor vasculatures. The CP NPs exhibit a large extinction coefficient of 48.1 L g^?1 at the absorption maximum of 1161 nm, with an ultrahigh PA sensitivity up to 2 µg mL^?1. 3D ORPAMI of wide‐field mice ear allows clear visualization of regular vasculatures with a resolution of 19.2 µm and an SBR of 29.3 dB at the maximal imaging depth of 539 µm. The margin of ear tumor composed of torsional dense vessels among surrounding normal regular vessels can be clearly delineated via 3D angiography. In addition, 3D whole‐cortex cerebral vasculatures with large imaging area (48 mm²), good resolution (25.4 µm), and high SBR (22.3 dB) at a depth up to 1001 µm are clearly resolved through the intact skull. These results are superior to the recently reported 3D NIR‐II fluorescence confocal vascular imaging, which opens up new opportunities for NIR‐II CP‐NP‐assisted ORPAMI in various biomedical applications.     

Cu2MoS4/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, Cu₂MoS₄ (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.     

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

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

Semiconducting Polymer Nanoparticles for Centimeters‐Deep Photoacoustic Imaging in the Second Near‐Infrared Window

Thienoisoindigo‐based semiconducting polymer with a strong near‐infrared absorbance is synthesized and its water‐dispersed nanoparticles (TSPNs) are investigated as a contrast agent for photoacoustic (PA) imaging in the second near‐infrared (NIR‐II) window (1000–1350 nm). The TSPNs generate a strong PA signal in the NIR‐II optical window, where background signals from endogenous contrast agents, including blood and lipid, are at the local minima. By embedding a TSPN‐containing tube in chicken‐breast tissue, an imaging depth of more than 5 cm at 1064 nm excitation is achieved with a contrast‐agent concentration as low as 40 µg mL^?1. The TSPNs under the skin or in the tumor are clearly visualized at 1100 and 1300 nm, with negligible interference from the tissue background. TSPN as a PA contrast in the NIR‐II window opens new opportunities for biomedical imaging of deep tissues with improved contrast.     

Biosynthesis of Melanin Nanoparticles for Photoacoustic Imaging Guided Photothermal Therapy

Photothermal therapy (PTT) has attracted considerable attention in recent years due to their unique advantages in minimal invasiveness and spatiotemporal selectivity. However, the fabrication procedures of PTT agents frequently require complex chemical and/or physical methods that involves harsh and environmentally hazardous conditions. Here, a genetically engineered bacterium is developed to synthesize melanin nanoparticles under mild and environmentally friendly conditions. The biosynthetic melanin nanoparticles exhibit excellent biocompatibility, good stability, and negligible toxicity. In addition, the biosynthetic melanin nanoparticles have strong absorption at near-infrared (NIR) region and higher photothermal conversion efficiency (48.9%) than chemically synthesized melanin-like polydopamine nanoparticles under an 808 nm laser irradiation. Moreover, the results show that the biosynthetic melanin nanoparticles have excellent photoacoustic imaging (PAI) performance and can be used for PAI guided PTT in vivo. In conclusion, the study provides an alternative approach to synthesize PTT agents with broad application potential in the diagnosis and treatment of cancer.     

Functionalized NIR‐II Semiconducting Polymer Nanoparticles for Single‐cell to Whole‐Organ Imaging of PSMA‐Positive Prostate Cancer

Development of molecular probes holds great promise for early diagnosis of aggressive prostate cancer. Here, 2‐[3‐(1,3‐dicarboxypropyl) ureido] pentanedioic acid (DUPA)‐conjugated ligand and bis‐isoindigo‐based polymer (BTII) are synthesized to formulate semiconducting polymer nanoparticles (BTII‐DUPA SPN) as a prostate‐specific membrane antigen (PSMA)‐targeted probe for prostate cancer imaging in the NIR‐II window. Insights into the interaction of the imaging probes with the biological targets from single cell to whole organ are obtained by transient absorption (TA) microscopy and photoacoustic (PA) tomography. At single‐cell level, TA microscopy reveals the targeting efficiency, kinetics, and specificity of BTII‐DUPA SPN to PSMA‐positive prostate cancer. At organ level, PA tomographic imaging of BTII‐DUPA SPN in the NIR‐II window demonstrates superior imaging depth and contrast. By intravenous administration, BTII‐DUPA SPN demonstrates selective accumulation and retention in the PSMA‐positive tumor, allowing noninvasive PA detection of PSMA overexpressing prostate tumors in vivo. The distribution of nanoparticles inside the tumor tissue is further analyzed through TA microscopy. These results collectively demonstrate BTII‐DUPA SPN as a promising probe for prostate cancer diagnosis by PA tomography.     

A Rationally Designed Semiconducting Polymer Brush for NIR‐II Imaging‐Guided Light‐Triggered Remote Control of CRISPR/Cas9 Genome Editing

The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR‐associated protein 9 (Cas9) genome‐editing system has shown great potential in biomedical applications. Although physical approaches, viruses, and some nonviral vectors have been employed for CRISPR/Cas9 delivery and induce some promising genome‐editing efficacy, precise genome editing remains challenging and has not been reported yet. Herein, second near‐infrared window (NIR‐II) imaging‐guided NIR‐light‐triggered remote control of the CRISPR/Cas9 genome‐editing strategy is reported based on a rationally designed semiconducting polymer brush (SPPF). SPPF can not only be a vector to deliver CRISPR/Cas9 cassettes but also controls the endolysosomal escape and payloads release through photothermal conversion under laser irradiation. Upon laser exposure, the nanocomplex of SPPF and CRISPR/Cas9 cassettes induces effective site‐specific precise genome editing both in vitro and in vivo with minimal toxicity. Besides, NIR‐II imaging based on SPPF can also be applied to monitor the in vivo distribution of the genome‐editing system and guide laser irradiation in real time. Thus, this study offers a typical paradigm for NIR‐II imaging‐guided NIR‐light‐triggered remote control of the CRISPR/Cas9 system for precise genome editing. This strategy may open an avenue for CRISPR/Cas9 genome‐editing‐based precise gene therapy in the near future.     

A New Co‐P Nanocomposite with Ultrahigh Relaxivity for In Vivo Magnetic Resonance Imaging‐Guided Tumor Eradication by Chemo/Photothermal Synergistic Therapy

Design of new nanoagents that intrinsically have both diagnostic imaging and therapeutic capabilities is highly desirable for personalized medicine. In this work, a novel nanotheranostic agent is fabricated based on polydopamine (PDA)‐functionalized Co‐P nanocomposites (Co‐P@PDA) for magnetic resonance imaging (MRI)‐guided combined photothermal therapy and chemotherapy. The ultrahigh relaxivity of 224.61 mm ^?1 s^?1 can enable Co‐P@PDA to be applied as an excellent contrast agent for MRI in vitro and in vivo, providing essential and comprehensive information for tumor clinical diagnosis. Moreover, Co‐P@PDA exhibit excellent photothermal performance owing to the strong near‐infrared (NIR) absorbance of both Co‐P nanocomposite and PDA. Highly effective ablation of tumors is achieved in a murine tumor model because the NIR laser not only induces photothermal effects but also triggers the chemotherapeutic drug on‐demand release, which endows the Co‐P@PDA with high curative effects but little toxicity and few side effects. These findings demonstrate that Co‐P@PDA are promising agents for highly effective and precise antitumor treatment and warrant exploration as novel theranostic nanoagents with good potential for future clinical translation.