Drug-induced acute kidney injury (AKI) with a high morbidity and mortality is poorly diagnosed in hospitals and deficiently evaluated in drug discovery. Here, we report the development of molecular ...renal probes (MRPs) with high renal clearance efficiency for in vivo optical imaging of drug-induced AKI. MRPs specifically activate their near-infrared fluorescence or chemiluminescence signals towards the prodromal biomarkers of AKI including the superoxide anion, N-acetyl-β-D-glucosaminidase and caspase-3, enabling an example of longitudinal imaging of multiple molecular events in the kidneys of living mice. Importantly, they in situ report the sequential occurrence of oxidative stress, lysosomal damage and cellular apoptosis, which precedes clinical manifestation of AKI (decreased glomerular filtration). Such an active imaging mechanism allows MRPs to non-invasively detect the onset of cisplatin-induced AKI at least 36 h earlier than the existing imaging methods. MRPs can also act as exogenous tracers for optical urinalysis that outperforms typical clinical/preclinical assays, demonstrating their clinical promise for early diagnosis of AKI.
Molecular probes that change their signals in response to the target of interest have a critical role in fundamental biology and medicine. Semiconducting polymer nanoparticles (SPNs) have recently ...emerged as a new generation of purely organic photonic nanoagents with desirable properties for biological applications. In particular, tunable optical properties of SPNs allow them to be developed into photoluminescence, chemiluminescence, and photoacoustic probes, wherein SPNs usually serve as the energy donor and internal reference for luminescence and photoacoustic probes, respectively. Moreover, facile surface modification and intraparticle engineering provide the versatility to make them responsive to various biologically and pathologically important substances and indexes including small‐molecule mediators, proteins, pH and temperature. This article focuses on recent advances in the development of SPN‐based activatable molecular probes for sensing and imaging. The designs and applications of these probes are discussed in details, and the present challenges to further advance them into life science are also analyzed.
Semiconducting polymer nanoparticles (SPNs) have shown great promise in life science. Recent advances of developing SPNs into smart activatable probes for biological sensing and molecular imaging are discussed.
Smart molecular probes that emit deep‐tissue penetrating photoacoustic (PA) signals responsive to the target of interest are imperative to understand disease pathology and develop innovative ...therapeutics. This study reports a self‐assembly approach to develop semiconducting macromolecular activatable probe for in vivo imaging of reactive oxygen species (ROS). This probe comprises a near‐infrared absorbing phthalocyanine core and four poly(ethylene glycol) (PEG) arms linked by ROS‐responsive self‐immolative segments. Such an amphiphilic macromolecular structure allows it to undergo an ROS‐specific cleavage process to release hydrophilic PEG and enhance the hydrophobicity of the nanosystem. Consequently, the residual phthalocyanine component self‐assembles and regrows into large nanoparticles, leading to ROS‐enhanced PA signals. The small size of the intact macromolecular probe is beneficial to penetrate into the tumor tissue of living mice, while the ROS‐activated regrowth of nanoparticles prolongs the retention along with enhanced PA signals, permitting imaging of ROS during chemotherapy. This study thus capitalizes on stimuli‐controlled self‐assembly of macromolecules in conjunction with enhanced heat transfer in large nanoparticles for the development of smart molecular probes for PA imaging.
A semiconducting macromolecular probe (PCBP) that can self‐assemble into large nanoparticles in the presence of reactive oxygen species (ROS) is synthesized for photoacoustic (PA) molecular imaging. The small size and intact nanostructure of PCBP permit the tumor to be targeted passively, while the ROS‐activated regrowth of nanoparticles prolongs the retention and enhances the PA signals in the tumor site.
Phototheranostic nanoagents are promising for early diagnosis and precision therapy of cancer. However, their imaging ability and therapeutic efficacy are often limited due to the presence of ...delivery barriers in the tumor microenvironment. Herein, we report the development of organic multimodal phototheranostic nanoagents that can biomimetically target cancer-associated fibroblasts in the tumor microenvironment for enhanced multimodal imaging-guided cancer therapy. Such biomimetic nanocamouflages comprise a near-infrared (NIR) absorbing semiconducting polymer nanoparticle (SPN) coated with the cell membranes of activated fibroblasts. The homologous targeting mechanism allows the activated fibroblast cell membrane coated SPN (AF-SPN) to specifically target cancer-associated fibroblasts, leading to enhanced tumor accumulation relative to the uncoated and cancer cell membrane coated counterparts after systemic administration in living mice. As such, AF-SPN not only provides stronger NIR fluorescence and photoacoustic signals to detect tumors but also generates enhanced cytotoxic heat and singlet oxygen to exert combinational photothermal and photodynamic therapy, ultimately leading to an antitumor efficacy higher than that of the counterparts. This study introduces an organic phototheranostic system that biomimetically targets the component in the tumor microenvironment for enhanced multimodal cancer theranostics.
Optical theranostic nanoagents that seamlessly and synergistically integrate light-generated signals with photothermal or photodynamic therapy can provide opportunities for cost-effective precision ...medicine, while the potential for clinical translation requires them to have good biocompatibility and high imaging/therapy performance. We herein report an intraparticle molecular orbital engineering approach to simultaneously enhance photoacoustic brightness and photothermal therapy efficacy of semiconducting polymer nanoparticles (SPNs) for in vivo imaging and treatment of cancer. The theranostic SPNs have a binary optical component nanostructure, wherein a near-infrared absorbing semiconducting polymer and an ultrasmall carbon dot (fullerene) interact with each other to induce photoinduced electron transfer upon light irradiation. Such an intraparticle optoelectronic interaction augments heat generation and consequently enhances the photoacoustic signal and maximum photothermal temperature of SPNs by 2.6- and 1.3-fold, respectively. With the use of the amplified SPN as the theranostic nanoagent, it permits enhanced photoacoustic imaging and photothermal ablation of tumor in living mice. Our study thus not only introduces a category of purely organic optical theranostics but also highlights a molecular guideline to amplify the effectiveness of light-intensive imaging and therapeutic nanosystems.
Optogenetics provides powerful means for precise control of neuronal activity; however, the requirement of transgenesis and the incapability to extend the neuron excitation window into the ...deep-tissue-penetrating near-infrared (NIR) region partially limit its application. We herein report a potential alternative approach to optogenetics using semiconducting polymer nanobioconjugates (SPNsbc) as the photothermal nanomodulator to control the thermosensitive ion channels in neurons. SPNsbc are designed to efficiently absorb the NIR light at 808 nm and have a photothermal conversion efficiency higher than that of gold nanorods. By virtue of the fast heating capability in conjunction with the precise targeting to the thermosensitive ion channel, SPNsbc can specifically and rapidly activate the intracellular Ca2+ influx of neuronal cells in a reversible and safe manner. Our study provides an organic nanoparticle based strategy that eliminates the need for genetic transfection to remotely regulate cellular machinery.
The detection of exosomes is promising for the early diagnosis of cancer. However, the development of suitable optical sensors remains challenging. We have developed the first luminescent nanosensor ...for the multiplex differentiation of cancer exosomes that bypasses real‐time light excitation. The sensor is composed of a near‐infrared semiconducting polyelectrolyte (ASPN) that forms a complex with a quencher‐tagged aptamer. The afterglow signal of the nanocomplex (ASPNC), being initially quenched, is turned on in the presence of aptamer‐targeted exosomes. Because detection of the afterglow takes place after the excitation, background signals are minimized, leading to an improved limit of detection that is nearly two orders of magnitude lower than that of fluorescence detection in cell culture media. Also, ASPNC can be easily tailored to detect different exosomal proteins by changing the aptamer sequence. This enables an orthogonal analysis of multiple exosome samples, potentially permitting an accurate identification of the cellular origin of exosomes for cancer diagnosis.
Let there be light: The first luminescent nanosensor that bypasses real‐time light excitation for the multiplex differentiation of cancer exosomes is reported. It is composed of a near‐infrared semiconducting polyelectrolyte in complex with a quencher‐tagged aptamer.
Photoacoustic (PA) imaging and photothermal therapy (PTT) provide useful tools for diagnosis and treatments of diseases. However, current applications of PA imaging and PTT are greatly limited by ...their relying on light source in the first near‐infrared (NIR) window (NIR‐I, 750–1000 nm), which shows shallow tissue penetration depth. Recently, this predicament is addressed by the use of second NIR (NIR‐II) light ranging from 1000 to 1700 nm due to reduced light–tissue interaction and increased allowable power density for light irradiation. Since a few endogenous biomolecules can absorb or emit NIR‐II light, it is necessary to develop contrast and therapeutic agents used for PA imaging and PTT in the NIR‐II window. This review summarizes the recent progresses of NIR‐II absorbing optical agents for PA imaging and PTT in living animal models. The prominent performance of NIR‐II PA imaging and NIR‐II PTT is first introduced with the use of optical agents, followed by discussion of the applications of NIR‐II PTT under the guidance of NIR‐I or NIR‐II PA imaging. At last, challenges and perspectives of NIR‐II absorbing optical agents for PA imaging and PTT are proposed.
The recent progress of second near‐infrared (NIR‐II) absorbing agents for photoacoustic (PA) imaging and photothermal therapy (PTT) is summarized here. Due to the deeper tissue penetration and higher maximum permissible exposure of NIR‐II light over NIR‐I light, NIR‐II PA imaging and NIR‐II PTT show improved diagnostic and therapeutic efficacy.
Detection of metastatic tumor tissues is crucial for cancer therapy; however, fluorescence agents that allow to do share the disadvantage of low signal‐to‐background ratio due to tissue ...autofluorescence. The development of amphiphilic poly(p‐phenylenevinylene) derivatives that can self‐assemble into the nanoagent (SPPVN) in biological solutions and emit near‐infrared afterglow luminescence after cessation of light irradiation for ultrasensitive imaging of metastatic tumors in living mice is herein reported. As compared with the counterpart nanoparticle (PPVP) prepared from the hydrophobic PPV derivate, SPPVN has smaller size, higher energy transfer efficiency, and brighter afterglow luminescence. Moreover, due to the higher PEG density of SPPVN relative to PPVP poly(ethylene glycol), SPPVN has a better accumulation in tumor. Such a high sensitivity and ideal biodistribution allow SPPVN to rapidly detect xenograft tumors with the size as small as 1 mm3 and tiny peritoneal metastatic tumors that are almost invisible to naked eye, which is not possible for PPVP. Moreover, the oxygen‐sensitive afterglow makes SPPVN potentially useful for in vivo imaging of oxygen levels. By virtue of enzymatic biodegradability and ideal in vivo clearance, these organic agents can serve as a platform for the construction of advanced afterglow imaging tools.
Self‐assembled semiconducting polymer nanoparticles with a near‐infrared afterglow are developed for ultrasensitive tumor imaging. Due to their small size, stable nanostructure, and excitation‐free luminescence, they can favorably accumulate in tumors, delineating xenograft tumors and tiny peritoneal metastatic tumors in living mice.
Photoacoustic (PA) imaging holds great promise for preclinical research and clinical practice. However, most studies rely on the laser wavelength in the first near-infrared (NIR) window (NIR-I, ...650–950 nm), while few studies have been exploited in the second NIR window (NIR-II, 1000–1700 nm), mainly due to the lack of NIR-II absorbing contrast agents. We herein report the synthesis of a broadband absorbing PA contrast agent based on semiconducting polymer nanoparticles (SPN-II) and apply it for PA imaging in NIR-II window. SPN-II can absorb in both NIR-I and NIR-II regions, providing the feasibility to directly compare PA imaging at 750 nm with that at 1064 nm. Because of the weaker background PA signals from biological tissues in NIR-II window, the signal-to-noise ratio (SNR) of SPN-II resulted PA images at 1064 nm can be 1.4-times higher than that at 750 nm when comparing at the imaging depth of 3 cm. The proof-of-concept application of NIR-II PA imaging is demonstrated in in vivo imaging of brain vasculature in living rats, which showed 1.5-times higher SNR as compared with NIR-I PA imaging. Our study not only introduces the first broadband absorbing organic contrast agent that is applicable for PA imaging in both NIR-I and NIR-II windows but also reveals the advantages of NIR-II over NIR-I in PA imaging.
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