Near‐Infrared Excitation/Emission and Multiphoton‐Induced Fluorescence of Carbon Dots

Carbon dots (CDs) have significant potential for use in various fields including biomedicine, bioimaging, and optoelectronics. However, inefficient excitation and emission of CDs in both near‐infrared (NIR‐I and NIR‐II) windows remains an issue. Solving this problem would yield significant improvement in the tissue‐penetration depth for in vivo bioimaging with CDs. Here, an NIR absorption band and enhanced NIR fluorescence are both realized through the surface engineering of CDs, exploiting electron‐acceptor groups, namely molecules or polymers rich in sulfoxide/carbonyl groups. These groups, which are bound to the outer layers and the edges of the CDs, influence the optical bandgap and promote electron transitions under NIR excitation. NIR‐imaging information encryption and in vivo NIR fluorescence imaging of the stomach of a living mouse using CDs modified with poly(vinylpyrrolidone) in aqueous solution are demonstrated. In addition, excitation by a 1400 nm femtosecond laser yields simultaneous two‐photon‐induced NIR emission and three‐photon‐induced red emission of CDs in dimethyl sulfoxide. This study represents the realization of both NIR‐I excitation and emission as well as two‐photon‐ and three‐photon‐induced fluorescence of CDs excited in an NIR‐II window, and provides a rational design approach for construction and clinical applications of CD‐based NIR imaging agents.     

Thermally Activated Upconversion Near‐Infrared Photoluminescence from Carbon Dots Synthesized via Microwave Assisted Exfoliation

Upconversion near‐infrared (NIR) fluorescent carbon dots (CDs) are important for imaging applications. Herein, thermally activated upconversion photoluminescence (UCPL) in the NIR region, with an emission peak at 784 nm, which appears under 808 nm continuous‐wave laser excitation, are realized in the NIR absorbing/emissive CDs (NIR‐CDs). The NIR‐CDs are synthesized by microwave‐assisted exfoliation of red emissive CDs in dimethylformamide, and feature single or few‐layered graphene‐like cores. This structure provides an enhanced contact area of the graphene‐like plates in the core with the electron‐acceptor carbonyl groups in dimethylformamide, which contributes to the main NIR absorption band peaked at 724 nm and a tail band in 800–850 nm. Temperature‐dependent photoluminescence spectra and transient absorption spectra confirm that the UCPL of NIR‐CDs is due to the thermally activated electron transitions in the excited state, rather than the multiphoton absorption process. Temperature dependent upconversion NIR luminescence imaging is demonstrated for NIR‐CDs embedded in a polyvinyl pyrrolidone film, and the NIR upconversion luminescence imaging in vivo using NIR‐CDs in a mouse model is accomplished.     

UV–Vis–NIR Full‐Range Responsive Carbon Dots with Large Multiphoton Absorption Cross Sections and Deep‐Red Fluorescence at Nucleoli and In Vivo

Carbon dots (CDs), with excellent optical property and cytocompatibility, are an ideal class of nanomaterials applied in the field of biomedicine. However, the weak response of CDs in the near‐infrared (NIR) region impedes their practical applications. Here, UV–vis–NIR full‐range responsive fluorine and nitrogen doped CDs (N‐CDs‐F) are designed and synthesized that own a favorable donor‐π‐acceptor (D‐π‐A) configuration and exhibit excellent two‐photon (λ_ex = 1060 nm), three‐photon (λ_ex = 1600 nm), and four‐photon (λ_ex = 2000 nm) excitation upconversion fluorescence. D‐π‐A‐conjugated CDs prepared by solvothermal synthesis under the assistance of ammonia fluoride are reported and are endowed with larger multiphoton absorption (MPA) cross sections (3PA: 9.55 × 10^?80 cm⁶ s² photon^?2, 4PA: 6.32 × 10^?80 cm⁸ s³ photon^?3) than conventional organic compounds. Furthermore, the N‐CDs‐F show bright deep‐red to NIR fluorescence both in vitro and in vivo, and can even stain the nucleoli of tumor cells. A plausible mechanism is proposed on the basis of the strong inter‐dot and intra‐dot hydrogen bonds through N? H···F that can facilitate the expanding of conjugated sp² domains, and thus not only result in lower highest occupied molecular orbital‐lowest unoccupied molecular orbital energy level but also larger MPA cross sections than those of undoped CDs.     

Carbon Dots‐in‐Matrix Boosting Intriguing Luminescence Properties and Applications

As a new class of luminescent nanomaterials, carbon dots (CDs) have aroused significant interest because of their fascinating photoluminescence properties and potential applications in biological, optoelectronic, and energy‐related fields. Strikingly, embedding CDs in host matrices endow them with intriguing luminescent properties, in particular, room temperature phosphorescence and thermally activated delayed fluorescence, due to the confinement effect of the host matrix and the H‐bonding interactions between CDs and the matrix. Here, the state‐of‐the‐art strategies for introducing CDs in various host matrices are summarized, such as nanoporous materials, polyvinyl alcohol, polyurethane, potash alum, layered double hydroxides, amorphous silica, etc. The resultant luminescent properties of the composites and their emission mechanisms are discussed. Their applications in bioimaging, drug delivery/release, sensing, and anticounterfeiting are also presented. Finally, current problems and challenges of CDs‐based composites are noted for future development of such luminescent materials.     

Sub‐10‐nm Pd Nanosheets with Renal Clearance for Efficient Near‐Infrared Photothermal Cancer Therapy

Efficient renal clearance is of fundamentally important property of nanoparticles for their in vivo biomedical applications. In this work, we report the successful synthesis of ultra‐small Pd nanosheets (SPNS) with an average diameter of 4.4 nm and their application in photothermal cancer therapy using a near infrared laser. The ultra‐small Pd nanosheets have strong optical absorption in the NIR region and high photothermal conversion efficiency (52.0%) at 808 nm. After being surface‐functionalized with reduced glutathione (GSH), the SPNS‐GSH was administered to mice to investigate the biodistribution, photothermal efficacy and tumor ablation in vivo. The in vivo photothermal therapy studies clearly demonstrate that surface modification with GSH allows the nanosheets to exhibit prolonged blood circulation and thus high accumulation in tumors. Upon 808 nm NIR irradiation, the tumors can be completely ablated. More importantly, with the size below the renal filtration limit (<10 nm), the GSHylated Pd nanosheets can be nicely cleared from body through the renal excretion route and into urine. Together with the high efficacy of NIR photothermal therapy, the unique renal clearance properties make the ultra‐small Pd nanosheets promising for practical use in photothermal cancer therapy.     

Solvent‐Controlled Synthesis of Highly Luminescent Carbon Dots with a Wide Color Gamut and Narrowed Emission Peak Widths

Carbon dots (CDs) have tremendous potential applications in bioimaging, biomedicine, and optoelectronics. By far, it is still difficult to produce photoluminescence (PL) tunable CDs with high quantum yield (QY) across the entire visible spectrum and narrow the emission peak widths of CDs close to those of typical quantum dots. In this work, a series of CDs with tunable emission from 443 to 745 nm, quantum yield within 13–54%, and narrowed full width at half maximum (FWHM) from 108 to 55 nm, are obtained by only adjusting the reaction solvents in a one‐pot solvothermal route. The distinct optical features of these CDs are based on their differences in the particle size, and the content of graphitic nitrogen and oxygen‐containing functional groups, which can be modulated by controlling the dehydration and carbonization processes during solvothermal reactions. Blue, green, yellow, red, and even pure white light emitting films (Commission Internationale de L'Eclairage (CIE)= 0.33, 0.33, QY = 39%) are prepared by dispersing one or three kinds of CDs into polyvinyl alcohol with appropriate ratios. The near‐infrared emissive CDs are excellent fluorescent probes for both in vitro and in vivo bioimaging because of their high QY in water, long‐term stability, and low cytotoxicity.     

Solid‐State Carbon Dots with Red Fluorescence and Efficient Construction of Dual‐Fluorescence Morphologies

Stable solid‐state red fluorescence from organosilane‐functionalized carbon dots (CDs) with sizes around 3 nm is reported for the first time. Meanwhile, a novel method is also first reported for the efficient construction of dual‐fluorescence morphologies. The quantum yield of these solid‐state CDs and their aqueous solution is 9.60 and 50.7%, respectively. The fluorescence lifetime is 4.82 ns for solid‐state CDs, and 15.57 ns for their aqueous solution. These CDs are detailedly studied how they can exhibit obvious photoluminescence overcoming the self‐quenching in solid state. Luminescent materials are constructed with dual fluorescence based on as‐prepared single emissive CDs (red emission) and nonfluorescence media (starch, Al₂O₃, and RnOCH₃COONa), with the characteristic peaks located at nearly 440 and 600 nm. Tunable photoluminescence can be successfully achieved by tuning the mass ratio of CDs to solid matrix (such as starch). These constructed dual‐fluorescence CDs/starch composites can also be applied in white light‐emitting diodes with UV chips (395 nm), and oxygen sensing.     

Two‐Dimensional Nanomaterials for Biomedical Applications: Emerging Trends and Future Prospects

Two‐dimensional (2D) nanomaterials are ultrathin nanomaterials with a high degree of anisotropy and chemical functionality. Research on 2D nanomaterials is still in its infancy, with the majority of research focusing on elucidating unique material characteristics and few reports focusing on biomedical applications of 2D nanomaterials. Nevertheless, recent rapid advances in 2D nanomaterials have raised important and exciting questions about their interactions with biological moieties. 2D nanoparticles such as carbon‐based 2D materials, silicate clays, transition metal dichalcogenides (TMDs), and transition metal oxides (TMOs) provide enhanced physical, chemical, and biological functionality owing to their uniform shapes, high surface‐to‐volume ratios, and surface charge. Here, we focus on state‐of‐the‐art biomedical applications of 2D nanomaterials as well as recent developments that are shaping this emerging field. Specifically, we describe the unique characteristics that make 2D nanoparticles so valuable, as well as the biocompatibility framework that has been investigated so far. Finally, to both capture the growing trend of 2D nanomaterials for biomedical applications and to identify promising new research directions, we provide a critical evaluation of potential applications of recently developed 2D nanomaterials.     

A Novel Top‐Down Synthesis of Ultrathin 2D Boron Nanosheets for Multimodal Imaging‐Guided Cancer Therapy

Single atom nonmetal 2D nanomaterials have shown considerable potential in cancer nanomedicines, owing to their intriguing properties and biocompatibility. Herein, ultrathin boron nanosheets (B NSs) are prepared through a novel top‐down approach by coupling thermal oxidation etching and liquid exfoliation technologies, with controlled nanoscale thickness. Based on the PEGylated B NSs, a new photonic drug delivery platform is developed, which exhibits multiple promising features for cancer therapy and imaging, including: i) efficient NIR‐light‐to‐heat conversion with a high photothermal conversion efficiency of 42.5%, ii) high drug‐loading capacity and triggered drug release by NIR light and moderate acidic pH, iii) strong accumulation at tumor sites, iv) multimodal imaging properties (photoacoustic, photothermal, and fluorescence imaging), and v) complete tumor ablation and excellent biocompatibility. As far as it is known, this is the first report on the top‐down fabrication of ultrathin 2D B NSs by the combined thermal oxidation etching and liquid exfoliation, as well as their application as a multimodal imaging‐guided drug delivery platform. The newly prepared B NSs are also expected to provide a robust and useful 2D nanoplatform for various biomedical applications.     

Repurposing Cyanine NIR‐I Dyes Accelerates Clinical Translation of Near‐Infrared‐II (NIR‐II) Bioimaging

The significantly reduced tissue autofluorescence and scattering in the NIR‐II region (1000–1700 nm) opens many exciting avenues for detailed investigation of biological processes in vivo. However, the existing NIR‐II fluorescent agents, including many molecular dyes and inorganic nanomaterials, are primarily focused on complicated synthesis routes and unknown immunogenic responses with limited potential for clinical translation. Herein, the >1000 nm tail emission of conventional biocompatible NIR cyanine dyes with emission peaks at 700–900 nm is systematically investigated, and a type of bright dye for NIR‐II imaging with high potential for accelerating clinical translation is identified. The asymmetry of the π domain in the S₁ state of NIR cyanine dyes is proven to result in a twisted intramolecular charge‐transfer process and NIR‐II emission, establishing a general rule to guide future NIR‐I/II fluorophore synthesis. The screened NIR dyes are identified to possess a bright emission tail in the NIR‐II region along with high quantum yield, high molar‐extinction coefficient, rapid fecal excretion, and functional groups amenable for bioconjugation. As a result, NIR cyanine dyes can be used for NIR‐II imaging to afford superior contrast and real‐time imaging of several biological models, facilitating the translation of NIR‐II bioimaging to clinical theranostic applications.     

Bright Far‐Red/Near‐Infrared Conjugated Polymer Nanoparticles for In Vivo Bioimaging

A highly emissive far‐red/near‐infrared (FR/NIR) fluorescent conjugated polymer (CP), poly[(9,9‐dihexylfluorene)‐co‐2,1,3‐benzothiadiazole‐co‐4,7‐di(thiophen‐2‐yl)‐2,1,3‐benzothiadiazole] (PFBTDBT10) is designed and synthesized via Suzuki polymerization. Formulation of PFBTDBT10 using 1,2‐distearoyl‐sn‐glycero‐3‐phosphoethanolamine‐N‐[methoxy(polyethylene glycol)‐2000] (DSPE‐PEG₂₀₀₀) and DSPE‐PEG₅₀₀₀‐folate as the encapsulation matrix yielded CP‐loaded DSPE‐PEG‐folic acid nanoparticles (CPDP‐FA NPs) with bright FR/NIR fluorescence (27% quantum yield) and a large Stoke's shift of 233 nm in aqueous solution. CPDP‐FA NPs show improved thermal/photostabilities and larger Stoke's shifts as compared to commercially available quantum dots (Qdot 655) and organic dyes such as Alexa Fluor 555 and Rhodamine 6G. In vivo studies of CPDP‐FA NPs on a hepatoma H22 tumor‐bearing mouse model reveal that they could serve as an efficient FR/NIR fluorescent probe for targeted in vivo fluorescence imaging and cancer detection in a high contrast and specific manner. Together with the negligible in vivo toxicity, CPDP‐FA NPs are promising FR/NIR fluorescent probes for future in vivo applications.     

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.     

Multibuilding Block Janus Synthesized by Seed‐Mediated Self‐Assembly for Enhanced Photothermal Effects and Colored Brownian Motion in an Optical Trap

The asymmetrical features and unique properties of multibuilding block Janus nanostructures (JNSs) provide superior functions for biomedical applications. However, their production process is very challenging. This problem has hampered the progress of JNS research and the exploration of their applications. In this study, an asymmetrical multibuilding block gold/iron oxide JNS has been generated to enhance photothermal effects and display colored Brownian motion in an optical trap. JNS is formed by seed‐mediated self‐assembly of nanoparticle‐loaded thermocleavable micelles, where the hydrophobic backbones of the polymer are disrupted at high temperatures, resulting in secondary self‐assembly and structural rearrangement. The JNS significantly enhances photothermal effects compared to their homogeneous counterpart after near‐infrared (NIR) light irradiation. The asymmetrical distribution of gold and iron oxide within JNS also generates uneven thermophoretic force to display active colored Brownian rotational motion in a single‐beam gradient optical trap. These properties indicate that the asymmetrical JNS could be employed as a strong photothermal therapy mediator and a fuel‐free nanoscale Janus motor under NIR light.     

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.     

Triple‐Mode Emissions with Invisible Near‐Infrared After‐Glow from Cr3+‐Doped Zinc Aluminum Germanium Nanoparticles for Advanced Anti‐Counterfeiting Applications

Materials exhibiting persistent luminescence (PersL) have great prospect in optoelectronic and biomedical applications such as optical information storage, bio‐imaging, and so on. Unfortunately, PersL materials with multimode emission properties have been rarely reported, although they are expected to be very desirable in multilevel anti‐counterfeiting and encryption applications. Herein, Cr³⁺‐doped zinc aluminum germanium (ZAG:Cr) nanoparticles exhibiting triple‐mode emissions are designed and demonstrated. Upon exposure to steady 254 nm UV light, the ZAG:Cr nanoparticles yield steady bluish‐white emission. After turning off the UV light, the emission disappears quickly and the mode switches to transient near‐infrared (NIR) PersL emission at predominantly 690 nm. The transient NIR PersL emission which arises from Cr³⁺ is induced by non‐equivalent substitution of Ge⁴⁺. After persisting for 50 min, it can be retriggered by 980 nm photons due to the continuous trap depth distribution of ZAG:Cr between 0.65 and 1.07 eV. Inspired by the triple‐mode emissions from ZAG:Cr, multifunctional luminescent inks composed of ZAG:Cr nanoparticles are prepared, and high‐security labeling and encoding encryption properties are demonstrated. The results indicate that ZAG:Cr nanoparticles have great potential in anti‐counterfeiting and encryption applications, and the strategy and concept described here provide insights into the design of advanced anti‐counterfeiting materials.     

Atomic‐Precision Gold Clusters for NIR‐II Imaging

Near‐infrared II (NIR‐II) imaging at 1100–1700 nm shows great promise for medical diagnosis related to blood vessels because it possesses deep penetration and high resolution in biological tissue. Unfortunately, currently available NIR‐II fluorophores exhibit slow excretion and low brightness, which prevents their potential medical applications. An atomic‐precision gold (Au) cluster with 25 gold atoms and 18 peptide ligands is presented. The Au₂₅ clusters show emission at 1100–1350 nm and the fluorescence quantum yield is significantly increased by metal‐atom doping. Bright gold clusters can penetrate deep tissue and can be applied in in vivo brain vessel imaging and tumor metastasis. Time‐resolved brain blood‐flow imaging shows significant differences between healthy and injured mice with different brain diseases in vivo. High‐resolution imaging of cancer metastasis allows for the identification of the primary tumor, blood vessel, and lymphatic metastasis. In addition, gold clusters with NIR‐II fluorescence are used to monitor high‐resolution imaging of kidney at a depth of 0.61 cm, and the quantitative measurement shows 86% of the gold clusters are cleared from body without any acute or long‐term toxicity at a dose of 100 mg kg^?1.     

Assembling Defined DNA Nanostructure with Nitrogen‐Enriched Carbon Dots for Theranostic Cancer Applications

DNA nanostructures as scaffolds for drug delivery, biosensing, and bioimaging are hindered by its vulnerability in physiological settings, less favorable of incorporating arbitrary guest molecules and other desirable functionalities. Noncanonical self‐assembly of DNA nanostructures with small molecules in an alternative system is an attractive strategy to expand their applications in multidisciplinary fields and is rarely explored. This work reports a nitrogen‐enriched carbon dots (NCDs)‐mediated DNA nanostructure self‐assembly strategy. Given the excellent photoluminescence and photodynamic properties of NCDs, the obtained DNA/NCDs nanocomplex holds great potential for bioimaging and anticancer therapy. NCDs can mediate DNA nanoprism (NP^NCD) self‐assembly isothermally at a large temperature and pH range in a magnesium‐free manner. To explore the suitability of NP^NCD in potential biomedical applications, the cytotoxicity and cellular uptake efficiency of NP^NCD are evaluated. NP^NCD with KRAS siRNA (NP^NCDK) is further conjugated for KRAS‐mutated nonsmall cell lung cancer therapy. The NP^NCDK shows excellent gene knockdown efficiency and anticancer effect in vitro. The current study suggests that conjugating NCDs with programmable DNA nanostructures is a powerful strategy to endow DNA nanostructures with new functionalities, and NP^NCD may be a potential theranostic platform with further fine‐tuned properties of CDs such as near‐red fluorescence or photothermal activities.     

Near‐Infrared‐II Molecular Dyes for Cancer Imaging and Surgery

Fluorescence bioimaging affords a vital tool for both researchers and surgeons to molecularly target a variety of biological tissues and processes. This review focuses on summarizing organic dyes emitting at a biological transparency window termed the near‐infrared‐II (NIR‐II) window, where minimal light interaction with the surrounding tissues allows photons to travel nearly unperturbed throughout the body. NIR‐II fluorescence imaging overcomes the penetration/contrast bottleneck of imaging in the visible region, making it a remarkable modality for early diagnosis of cancer and highly sensitive tumor surgery. Due to their convenient bioconjugation with peptides/antibodies, NIR‐II molecular dyes are desirable candidates for targeted cancer imaging, significantly overcoming the autofluorescence/scattering issues for deep tissue molecular imaging. To promote the clinical translation of NIR‐II bioimaging, advancements in the high‐performance small molecule–derived probes are critically important. Here, molecules with clinical potential for NIR‐II imaging are discussed, summarizing the synthesis and chemical structures of NIR‐II dyes, chemical and optical properties of NIR‐II dyes, bioconjugation and biological behavior of NIR‐II dyes, whole body imaging with NIR‐II dyes for cancer detection and surgery, as well as NIR‐II fluorescence microscopy imaging. A key perspective on the direction of NIR‐II molecular dyes for cancer imaging and surgery is also discussed.     

Self‐Propelled Micro/Nanomotors for On‐Demand Biomedical Cargo Transportation

Micro/nanomotors (MNMs) are miniaturized machines that can perform assigned tasks at the micro/nanoscale. Over the past decade, significant progress has been made in the design, preparation, and applications of MNMs that are powered by converting different sources of energy into mechanical force, to realize active movement and fulfill on‐demand tasks. MNMs can be navigated to desired locations with precise controllability based on different guidance mechanisms. A considerable research effort has gone into demonstrating that MNMs possess the potential of biomedical cargo loading, transportation, and targeted release to achieve therapeutic functions. Herein, the recent advances of self‐propelled MNMs for on‐demand biomedical cargo transportation, including their self‐propulsion mechanisms, guidance strategies, as well as proof‐of‐concept studies for biological applications are presented. In addition, some of the major challenges and possible opportunities of MNMs are identified for future biomedical applications in the hope that it may inspire future research.     

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.