Self‐Assembly of Semiconducting Polymer Amphiphiles for In Vivo Photoacoustic Imaging

Despite the advantages of semiconducting polymer nanoparticles (SPNs) over other inorganic nanoparticles for photoacoustic (PA) imaging, their synthetic method is generally limited to nanoprecipitation, which is likely to cause the issue of nanoparticle dissociation. The synthesis of near‐infrared (NIR) absorbing semiconducting polymer amphiphiles (SPAs) that can spontaneously self‐assemble into homogeneous nanoparticles for in vivo PA imaging is reported. As compared with their counterpart nanoparticles (SPN1) prepared through nanoprecipitation, SPAs generally have higher fluorescence quantum yields but similar size and PA brightness, making them superior over SPN1. Optical and simulation studies reveal that the poly(ethylene glycol) (PEG) grafting density plays a critical role in determining the packing of SP segments inside the core of nanoparticles, consequently affecting the optical properties. The small size and structurally stable nanostructure, in conjunction with a dense PEG shell, allow SPAs to passively target tumors of living mice after systemic administration, permitting both PA and fluorescence imaging of the tumors at signals that are ≈1.5‐fold higher than that of liver. This study thus not only provides the first generation of amphiphilic optically active polymers for PA imaging, but also highlights the molecular guidelines for the development of organic NIR imaging nanomaterials.     

Biocompatible D–A Semiconducting Polymer Nanoparticle with Light‐Harvesting Unit for Highly Effective Photoacoustic Imaging Guided Photothermal Therapy

The development of nanotheranostic agents that integrate diagnosis and therapy for effective personalized precision medicine has obtained tremendous attention in the past few decades. In this report, biocompatible electron donor–acceptor conjugated semiconducting polymer nanoparticles (PPor‐PEG NPs) with light‐harvesting unit is prepared and developed for highly effective photoacoustic imaging guided photothermal therapy. To the best of our knowledge, it is the first time that the concept of light‐harvesting unit is exploited for enhancing the photoacoustic signal and photothermal energy conversion in polymer‐based theranostic agent. Combined with additional merits including donor–acceptor pair to favor electron transfer and fluorescence quenching effect after NP formation, the photothermal conversion efficiency of the PPor‐PEG NPs is determined to be 62.3%, which is the highest value among reported polymer NPs. Moreover, the as‐prepared PPor‐PEG NP not only exhibits a remarkable cell‐killing ability but also achieves 100% tumor elimination, demonstrating its excellent photothermal therapeutic efficacy. Finally, the as‐prepared water‐dispersible PPor‐PEG NPs show good biocompatibility and biosafety, making them a promising candidate for future clinical applications in cancer theranostics.     

Thermoresponsive Semiconducting Polymer Nanoparticles for Contrast‐Enhanced Photoacoustic Imaging

Photoacoustic (PA) agents with biomarker‐activated signals are developed to enhance the signal‐to‐background ratios (SBRs) for in vivo imaging; however, their SBRs still heavily rely on the concentration difference of biomarkers between diseased and normal tissues. By contrast, external stimuli can provide a remote way to noninvasively control the signal generation from the PA agents and in turn enhance SBR, which are less exploited. This study reports the development of thermoresponsive semiconducting polymer brush with poly(N,N‐dimethylacrylamide)‐r‐(hydroxypropyl acrylate) (PDMA‐r‐HPA) grafts for contrast‐enhanced in vivo imaging. Such a polymer is amphiphilic and can self‐assemble into the nanoparticle (termed as SPNph1) in an aqueous medium, and has lower critical solution temperatures (LCSTs) at 48 °C. Thus, SPNph1 not only has higher photothermal conversion efficiency than the control polymer without PDMA‐r‐HPA grafts, but also can undergo phase separation to form large nanoparticles, leading to enhanced PA signals above LCST. The thermoresponsive PA property of SPNph1 enables in situ remote manipulation of PA signals by photoirradiation to further enhance the tumor SBR. Thus, this study introduces a new generation of organic PA agents with thermoresponsive signal for high‐contrast in vivo imaging.     

All‐in‐One Phototheranostics: Single Laser Triggers NIR‐II Fluorescence/Photoacoustic Imaging Guided Photothermal/Photodynamic/Chemo Combination Therapy

Development of single near‐infrared (NIR) laser triggered phototheranostics for multimodal imaging guided combination therapy is highly desirable but is still a big challenge. Herein, a novel small‐molecule dye DPP‐BT is designed and synthesized, which shows strong absorption in the first NIR window (NIR‐I) and fluorescence emission in the second NIR region (NIR‐II). Such a dye not only acts as a dual‐modal contrast agent for NIR‐II fluorescence and photoacoustic (PA) imaging, but also serves as a combined therapeutic agent for photothermal therapy (PTT) and photodynamic therapy (PDT). The single NIR laser triggered all‐in‐one phototheranostic nanoparticles are constructed by encapsulating the dye DPP‐BT, chemotherapy drug DOX, and natural phase‐change materials with a folic acid functionalized amphiphile. Notably, under NIR laser irradiation, DOX can effectively release from such nanoparticles via NIR‐induced hyperthermia of DPP‐BT. By intravenous injection of such nanoparticles into Hela tumor‐bearing mice, the tumor size and location can be accurately observed via NIR‐II fluorescence/PA dual‐modal imaging. From in vitro and in vivo therapy results, such nanoparticles simultaneously present remarkable antitumor efficacy by PTT/PDT/chemo combination therapy, which is triggered by a single NIR laser. Overall, this work provides an innovative strategy to design and construct all‐in‐one nanoplatforms for clinical phototheranostics.     

Significant Enhancement of Photothermal and Photoacoustic Efficiencies for Semiconducting Polymer Nanoparticles through Simply Molecular Engineering

Semiconducting polymer nanoparticles (SP NPs) are employed as efficient nanoagents for “all‐in‐one” theranostic nanoplatforms with dual photoacoustic imaging (PAI) and photothermal therapy (PTT) functions based on their photothermal conversion effect. However, the mechanisms of tuning the PTT efficiency are still elusive, though several SP NPs with high photothermal efficiency are reported. Herein, two donor–acceptor (D–A) SP NPs PTIGSVS and PIIGSVS with the same donor unit but different acceptor units are designed and synthesized. Through tuning the acceptor unit, PTIGSVS shows more planar backbone structure, stronger D–A strength, redshifted absorption, enhanced extinction efficient, weakened emission properties, and more efficient nonradiative decay in comparison to the polymeric analogue PIIGSVS . Thus, PTIGSVS NPs present much higher photothermal conversion efficiencies (74%) than PIIGSVS NPs (11%), resulting in significantly enhanced in vitro and in vivo PAI and PTT performance. This contribution demonstrates that PTIGSVS NPs are superior PA/PTT agents for effective cancer theranostic and shed light on understanding the relationship between molecular structures and photothermal effect of CPs.     

Ultra‐Small Iron Oxide Doped Polypyrrole Nanoparticles for In Vivo Multimodal Imaging Guided Photothermal Therapy

Recently, near‐infrared (NIR) absorbing conjugated polymeric nanoparticles have received significant attention in photothermal therapy of cancer. Herein, polypyrrole (PPy), a NIR‐absorbing conjugate polymer, is used to coat ultra‐small iron oxide nanoparticles (IONPs), obtaining multifunctional IONP@PPy nanocomposite which is further modified by the biocompatible polyethylene glycol (PEG) through a layer‐by‐layer method to acquire high stability in physiological solutions. Utilizing the optical and magnetic properties of the yielded IONP@PPy‐PEG nanoparticles, in vivo magnetic resonance (MR) and photoacoustic imaging of tumor‐bearing mice are conducted, revealing strong tumor uptake of those nanoparticles after intravenous injection. In vivo photothermal therapy is then designed and carried out, achieving excellent tumor ablation therapeutic effect in mice experiments. These results promise the use of multifunctional NIR‐absorbing organic‐inorganic hybrid nanomaterials, such as IONP@PPy‐PEG presented here, for potential applications in cancer theranostics.     

Development of Citrate‐Based Dual‐Imaging Enabled Biodegradable Electroactive Polymers

Increasing occurrences of degenerative diseases, defective tissues, and severe cancers heighten the importance of advanced biomedical treatments, which in turn enhance the need for improved biomaterials with versatile theranostic functionalities yet using minimal design complexity. Leveraging the advantages of citrate chemistry, a multifunctional citrate‐based biomaterial platform is developed with both imaging and therapeutic capabilities utilizing a facile and efficient one‐pot synthesis. The resulting aniline tetramer doped biodegradable photoluminescent polymers (BPLPATs) not only possess programmable degradation profiles (<1 to > 6 months) and mechanical strengths (≈20 MPa to >400 MPa), but also present a combination of intrinsic fluorescence, photoacoustic (PA), and electrical conductivity properties. BPLPAT nanoparticles are able to label cells for fluorescence imaging and perform deep tissue detection with PA imaging. Coupled with significant photothermal performance, BPLPAT nanoparticles demonstrate great potential for thermal treatment and in vivo real‐time detection of cancers. The results on BPLPAT scaffolds demonstrate 3D high‐spatial‐resolution deep tissue PA imaging (23 mm), as well as promote growth and differentiation of PC‐12 nerve cells. It is envisioned that the biodegradable dual‐imaging‐enabled electroactive citrate‐based biomaterial platform will expand the currently available theranostic material systems and open new avenues for diversified biomedical and biological applications via the demonstrated multifunctionality.     

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

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

A Versatile Nanotheranostic Agent for Efficient Dual‐Mode Imaging Guided Synergistic Chemo‐Thermal Tumor Therapy

The integration of efficient imaging for diagnosis and synergistic tumor therapy into a single‐component nanoplatform is much promising for high efficacy tumor treatment but still in a great challenge. Herein, a smart and versatile nanotheranostic platform based on hollow mesoporous Prussian blue nanoparticles (HMPBs) with perfluoropentane (PFP) and doxorubicin (DOX) inside, has been designed, for the first time, to achieve the distinct in vivo synergistic chemo‐thermal tumor therapy and synchronous diagnosis and monitoring by ultrasound (US)/photoacoustic (PA) dual mode imaging. The prepared HMPBs show excellent photothermal conversion properties with large molar extinction coefficient (≈1.2 × 10¹¹m ^?1 cm^?1) and extremely high photothermal conversion efficiency (41.4%). Such a novel theranostic nanoplatform is expected to overcome the inevitable tumor recurrence and metastasis resulting from the inhomogeneous ablation of single thermal therapy, which will find a promising prospect in the application of noninvasive cancer therapy.     

Hierarchical Nanohybrids of Gold Nanorods and PGMA‐Based Polycations for Multifunctional Theranostics

Organic/inorganic nanohybrids hold great importance in fabricating multifunctional theranostics to integrate therapeutic functions with real‐time imaging. Although Au nanorods (NRs) have been employed for theranostics, complicated design of materials limits their practical applications. In this work, new multifunctional theranostic agents are designed and synthesized employing Au NRs with desirable near‐infrared absorbance as the cores. A facile “grafting‐onto” approach is put forward to prepare the series of hierarchical nanohybrids (Au‐PGEA and Au‐PGED) of Au NRs and poly(glycidyl methacrylate)‐based polycations. The resultant nanohybrids can be utilized as gene carriers with high gene transfection performances. The structural effect of polycations on gene transfection is investigated in detail, and Au‐PGEA with abundant hydroxyl groups on the surface exhibits superior performance. Au‐PGEA nanohybrids are further validated to possess remarkable capability of combined photothermal therapy (PTT) and gene therapy (GT) for complementary tumor treatment. Moreover, significantly enhanced computed tomography (CT)/photoacoustic (PA) signals are detected both in vitro and in vivo, verifying the potential of Au‐PGEA for dual‐modal imaging with precise and accurate information. Therefore, these multifunctional nanohybrids fabricated from a simple and straightforward strategy are promising for in vivo dual‐modal CT/PA imaging guided GT/PTT therapy with high antitumor efficacy.     

Photoacoustic Imaging of Embryonic Stem Cell‐Derived Cardiomyocytes in Living Hearts with Ultrasensitive Semiconducting Polymer Nanoparticles

Human embryonic stem cell‐derived cardiomyocytes (hESC‐CMs) have become promising tools to repair injured hearts. To achieve optimal outcomes, advanced molecular imaging methods are essential to accurately track these transplanted cells in the heart. In this study, it is demonstrated for the first time that a class of photoacoustic nanoparticles (PANPs) incorporating semiconducting polymers (SPs) as contrast agents can be used in the photoacoustic imaging (PAI) of transplanted hESC‐CMs in living mouse hearts. This is achieved by virtue of two benefits of PANPs. First, strong photoacoustic (PA) signals and specific spectral features of SPs allow PAI to sensitively detect and distinguish a small number of PANP‐labeled cells (2000) from background tissues. Second, the PANPs show a high efficiency for hESC‐CM labeling without adverse effects on cell structure, function, and gene expression. Assisted by ultrasound imaging, the delivery and engraftment of hESC‐CMs in living mouse hearts can be assessed by PANP‐based PAI with high spatial resolution (≈100 µm). In summary, this study explores and validates a novel application of SPs as a PA contrast agent to track labeled cells with high sensitivity and accuracy in vivo, highlighting the advantages of integrating PAI and PANPs to advance cardiac regenerative therapies.     

A New Single 808 nm NIR Light‐Induced Imaging‐Guided Multifunctional Cancer Therapy Platform

The NIR light‐induced imaging‐guided cancer therapy is a promising route in the targeting cancer therapy field. However, up to now, the existing single‐modality light‐induced imaging effects are not enough to meet the higher diagnosis requirement. Thus, the multifunctional cancer therapy platform with multimode light‐induced imaging effects is highly desirable. In this work, captopril stabilized‐Au nanoclusters Au₂₅(Capt)₁₈?(Au₂₅) are assembled into the mesoporous silica shell coating outside of Nd³⁺‐sensitized upconversion nanoparticles (UCNPs) for the first time. The newly formed Au₂₅ shell exhibits considerable photothermal effects, bringing about the photothermal imaging and photoacoustic imaging properties, which couple with the upconversion luminescence imaging. More importantly, the three light‐induced imaging effects can be simultaneously achieved by exciting with a single NIR light (808 nm), which is also the triggering factor for the photothermal and photodynamic cancer therapy. Besides, the nanoparticles can also present the magnetic resonance and computer tomography imaging effects due to the Gd³⁺ and Yb³⁺ ions in the UCNPs. Furthermore, due to the photodynamic and the photothermal effects, the nanoparticles possess efficient in vivo tumor growth inhibition under the single irradiation of 808 nm light. The multifunctional cancer therapy platform with multimode imaging effects realizes a true sense of light‐induced imaging‐guided cancer therapy.     

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

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

Gold Nanoframeworks with Mesopores for Raman–Photoacoustic Imaging and Photo‐Chemo Tumor Therapy in the Second Near‐Infrared Biowindow

Gold‐based nanostructures with tunable wavelength of localized surface plasmon resonance (LSPR) in the second near‐infrared (NIR‐II) biowindow receive increasing attention in phototheranostics. In view of limited progress on NIR‐II gold nanostructures, a particular liposome template‐guided route is explored to synthesize novel gold nanoframeworks (AuNFs) with large mesopores (≈40 nm) for multimodal imaging along with therapeutic robustness. The synthesized AuNFs exhibit strong absorbance in NIR‐II region, affording their capacity of NIR‐II photothermal therapy (PTT) and photoacoustic (PA) imaging for deep tumors. Functionalization of AuNFs with hyaluronic acid (HA) endows the targeting capacity for CD44‐overexpressed tumor cells while gatekeeping doxorubicin (DOX) loaded into mesopores. Conjugation of Raman reporter 4‐aminothiophenol (4‐ATP) onto AuNFs yields a surface‐enhanced Raman scattering (SERS) fingerprint for Raman spectroscopy/imaging. In vivo evaluation of HA‐4‐ATP‐AuNFs‐DOX on tumor‐bearing xenografts demonstrates its high efficacy in eradication of solid tumors in NIR‐II under PA–Raman dual image‐guided photo‐chemotherapy. Thus, current AuNFs offer versatile capabilities for phototheranostics.     

Engineering Gold Nanotubes with Controlled Length and Near‐Infrared Absorption for Theranostic Applications

Important aspects in engineering gold nanoparticles for theranostic applications include the control of size, optical properties, cytotoxicity, biodistribution, and clearance. In this study, gold nanotubes with controlled length and tunable absorption in the near‐infrared (NIR) region have been exploited for applications as photothermal conversion agents and in vivo photoacoustic imaging contrast agents. A length‐controlled synthesis has been developed to fabricate gold nanotubes (NTs) with well‐defined shape (i.e., inner void and open ends), high crystallinity, and tunable NIR surface plasmon resonance. A coating of poly(sodium 4‐styrenesulfonate) (PSS) endows the nanotubes with colloidal stability and low cytotoxicity. The PSS‐coated Au NTs have the following characteristics: i) cellular uptake by colorectal cancer cells and macrophage cells, ii) photothermal ablation of cancer cells using single wavelength pulse laser irradiation, iii) excellent in vivo photoacoustic signal generation capability and accumulation at the tumor site, iv) hepatobiliary clearance within 72 h postintravenous injection. These results demonstrate that these PSS‐coated Au NTs have the ideal attributes to develop their potential as effective and safe in vivo imaging nanoprobes, photothermal conversion agents, and drug delivery vehicles. To the best of knowledge, this is the first in vitro and in vivo study of gold nanotubes.     

Magnetic Targeting Enhanced Theranostic Strategy Based on Multimodal Imaging for Selective Ablation of Cancer

The booming development of nanomedicine offers great opportunities for cancer diagnostics and therapeutics. Herein, a magnetic targeting‐enhanced cancer theranostic strategy using a multifunctional magnetic‐plasmonic nano‐agent is developed, and a highly effective in vivo tumor photothermal therapy, which is carefully planed based on magnetic resonance (MR)/photoacoustic (PA) multimodal imaging, is realized. By applying an external magnetic field (MF) focused on the targeted tumor, a magnetic targeting mediated enhanced permeability and retention (MT‐EPR) effect is observed. While MR scanning provides tumor localization and reveals time‐dependent tumor homing of nanoparticles for therapeutic planning, photoacoustic imaging with higher spatial resolution allows noninvasive fine tumor margin delineation and vivid visualization of three dimensional distributions of theranostic nanoparticles inside the tumor. Utilizing the near‐infrared (NIR) plasmonic absorbance of those nanoparticles, selective photothermal tumor ablation, whose efficacy is predicted by real‐time infrared thermal imaging intra‐therapeutically, is carried out and then monitored by MR imaging for post‐treatment prognosis. Overall, this study illustrates the concept of imaging‐guided MF‐targeted photothermal therapy based on a multifunctional nano‐agent, aiming at optimizing therapeutic planning to achieve the most efficient cancer therapy.     

High‐Security Multifunctional Nano‐Bismuth‐Sphere‐Cluster Prepared from Oral Gastric Drug for CT/PA Dual‐Mode Imaging and Chemo‐Photothermal Combined Therapy In Vivo

Multifunctional nanoprobes that can be applied for real‐time monitoring or precision treatment of tumors have received wide interest among researchers. However, most of these nanoprobes are obtained through chemical synthesis, and thereby may contain toxic residues or harmful reagents. In this article, a nano‐bismuth‐sphere‐cluster (Bi) is synthesized via a one‐step method (after an irradiation with ultra‐violet) and is then applied in dual‐mode computed tomography/photoacoustic imaging. Bismuth potassium citrate granules, which is a common gastric drug that is highly safe and has a low price (<1 China Yuan/g), is used as the only raw material. The results show that the Bi cluster has good stability with sizes of about 25–55 nm, and a photothermal conversion efficiency as high as 39.67%. After being adsorbed onto doxorubicin, the Bi cluster can be used directly in animal experiments. Due to the effect of enhanced permeability and retention, the probe can easily enter tumor cells. Drug release can be controlled by a near‐infrared laser and the acidic environment of tumor cells, which indicates that the combined chemo‐photothermal therapy is achieved. This work presents a new dual‐mode bio‐imaging and combined chemo‐photothermal therapeutic nanoprobe that can be applied in theragnostics for tumors.     

BSA‐Mediated Synthesis of Bismuth Sulfide Nanotheranostic Agents for Tumor Multimodal Imaging and Thermoradiotherapy

Fabrication of ultrasmall single‐component omnipotent nanotheranostic agents integrated with multimodal imaging and multiple therapeutic functions becomes more and more practically relevant but challenging. In this article, sub 10 nm Bi₂S₃ biocompatible particles are prepared through a bovine serum albumin (BSA)‐mediated biomineralization process under ambient aqueous conditions. Owing to the ultrasmall size and colloidal stability, the resulting nanoparticles (NPs) present outstanding blood circulation behavior and excellent tumor targeting ability. Toward theranostic applications, the biosafety profile is carefully investigated. In addition, photothermal conversion is characterized for both photoacoustic imaging and photothermal treatment of cancers. Upon radiolabeling, the performance of the resulting particles for SPECT/CT imaging in vivo is also carried out. Additionally, different combinations of treatments are applied for evaluating the performance of the as‐prepared Bi₂S₃ NPs in photothermal‐ and radiotherapy of tumors. Due to the remarkable photothermal conversion efficiency and large X‐ray attenuation coefficient, the implanted tumors are completely eradicated through combined therapies, which highlights the potential of BSA‐capped Bi₂S₃ NPs as a novel multifunctional nanotheranostic agent.     

“All‐in‐One” Nanoparticles for Trimodality Imaging‐Guided Intracellular Photo‐magnetic Hyperthermia Therapy under Intravenous Administration

Great efforts have been devoted so far to combine nano‐magnetic hyperthermia and nano‐photothermal therapy to achieve encouraging additive therapeutic performance in vitro and in vivo with limitation to direct intratumoral injection and no guidance of multimodality molecular imaging. In this study, a novel multifunctional theranostic nanoplatform (MNP@PES‐Cy7/2‐DG) consisting of magnetic nanoparticles (MNPs), poly(3,4‐ethylenedioxythiophene):poly(4‐styrenesulfonate) (PES), Cyanine7 (Cy7), and 2‐deoxyglucose (2‐DG)‐polyethylene glycol is developed. They are then applied to combined photo‐magnetic hyperthermia therapy under intravenous administration that is simultaneously guided by trimodality molecular imaging. Remarkably, nanoparticles are found aggregated mainly in the cytoplasm of tumor cells in vitro and in vivo, and exhibit stealth‐like behavior with a long second‐phase blood circulation half‐life of 20.38 ± 4.18 h. Under the guidance of photoacoustic/near‐infrared fluorescence/magnetic resonance trimodality imaging, tumors can be completely eliminated under intracellular photo‐magnetic hyperthermia therapy with additive therapeutic effect due to precise hyperthermia. This study may promote a further exploration of such a platform for clinical applications.     

Ultrasmall Semiconducting Polymer Dots with Rapid Clearance for Second Near‐Infrared Photoacoustic Imaging and Photothermal Cancer Therapy

Phototheranostic agents in the second near‐infrared (NIR‐II) window (1000–1700 nm) are emerging as a promising theranostic platform for precision medicine due to enhanced penetration depth and minimized tissue exposure. The development of metabolizable NIR‐II nanoagents for imaging‐guided therapy are essential for noninvasive disease diagnosis and precise ablation of tumors. Herein, metabolizable highly absorbing NIR‐II conjugated polymer dots (Pdots) are reported for the first time for photoacoustic imaging guided photothermal therapy (PTT). The unique design of low‐bandgap D‐A π‐conjugated polymer (DPP‐BTzTD) together with modified nanoreprecipitation conditions allows to fabricate NIR‐II absorbing Pdots with ultrasmall (4 nm) particle size. Extensive experimental tests demonstrate that the constructed Pdots exhibit good biocompatibility, excellent photostability, bright photoacoustic signals, and high photothermal conversion efficiency (53%). In addition, upon tail‐vein intravenous injection of tumor‐bearing mice, Pdots also show high‐efficient tumor ablation capability with rapid excretion from the body. In particular, both in vitro and in vivo assays indicate that the Pdots possess remarkable PTT performance under irradiation with a 1064 nm laser with 0.5 W cm^?2, which is much lower than its maximum permissible exposure limit of 1 W cm^?2. This pilot study thus paves a novel avenue for the development of organic semiconducting nanoagents for future clinical translation.