Yuyan Jiang

Broadband Absorbing Semiconducting Polymer Nanoparticles for Photoacoustic Imaging in Second Near-Infrared Window

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.

Advanced Photoacoustic Imaging Applications of Near‐Infrared Absorbing Organic Nanoparticles

Progress of nanotechnology in recent years has stimulated fast development of nanoparticles in biomedical research. Photoacoustic (PA) imaging as an emerging non-invasive technique in molecular imaging has improved imaging depth relative to conventional optical imaging, demonstrating great potential in clinical applications. The convergence of nanotechnology and PA imaging has enabled a broad spectrum of new opportunities in fundamental biology and translation medicine. This review focuses on the recent advances of organic nanoparticles in PA imaging applications. Near-infrared absorbing organic nanoparticles are classified and discussed according to their different imaging applications, which include tumor imaging, gastrointestinal imaging, sentinel lymph node imaging, disease microenvironment imaging and real-time drug imaging. The chemistry and PA properties of organic nanoparticles are discussed in details to highlight their own merits, and their challenges and perspectives in PA imaging are also discussed.

Amphiphilic semiconducting polymer as multifunctional nanocarrier for fluorescence/photoacoustic imaging guided chemo-photothermal therapy

Chemo-photothermal nanotheranostics has the advantage of synergistic therapeutic effect, providing opportunities for optimized cancer therapy. However, current chemo-photothermal nanotheranostic systems generally comprise more than three components, encountering the potential issues of unstable nanostructures and unexpected conflicts in optical and biophysical properties among different components. We herein synthesize an amphiphilic semiconducting polymer (PEG-PCB) and utilize it as a multifunctional nanocarrier to simplify chemo-photothermal nanotheranostics. PEG-PCB has a semiconducting backbone that not only serves as the diagnostic component for near-infrared (NIR) fluorescence and photoacoustic (PA) imaging, but also acts as the therapeutic agent for photothermal therapy. In addition, the hydrophobic backbone of PEG-PCB provides strong hydrophobic and π-π interactions with the aromatic anticancer drug such as doxorubicin for drug encapsulation and delivery. Such a trifunctionality of PEG-PCB eventually results in a greatly simplified nanotheranostic system with only two components but multimodal imaging and therapeutic capacities, permitting effective NIR fluorescence/PA imaging guided chemo-photothermal therapy of cancer in living mice. Our study thus provides a molecular engineering approach to integrate essential properties into one polymer for multimodal nanotheranostics.

Enhancing Both Biodegradability and Efficacy of Semiconducting Polymer Nanoparticles for Photoacoustic Imaging and Photothermal Therapy

Theranostic nanoagents are promising for precision medicine. However, biodegradable nanoagents with the ability for photoacoustic (PA) imaging guided photothermal therapy (PTT) are rare. We herein report the development of biodegradable semiconducting polymer nanoparticles (SPNs) with enhanced PA and PTT efficacy for cancer therapy. The design capitalizes on the enzymatically oxidizable nature of vinylene bonds in conjunction with polymer chemistry to synthesize a biodegradable semiconducting polymer (DPPV) and transform it into water-soluble nanoparticles (SPNV). As compared with its counterpart SPN (SPNT), the presence of vinylene bonds within the polymer backbone also endows SPNV with a significantly enhanced mass absorption coefficient (1.3-fold) and photothermal conversion efficacy (2.4-fold). As such, SPNV provides the PA signals and the photothermal maximum temperature higher than SPNT, allowing detection and photothermal ablation of tumors in living mice in a more sensitive and effective way. Our study thus reveals a general molecular design to enhance the biodegradability of optically active polymer nanoparticles while dramatically elevating their imaging and therapeutic capabilities.

Dual‐Peak Absorbing Semiconducting Copolymer Nanoparticles for First and Second Near‐Infrared Window Photothermal Therapy: A Comparative Study

Near-infrared (NIR) light is widely used for noninvasive optical diagnosis and phototherapy. However, current research focuses on the first NIR window (NIR-I, 650-950 nm), while the second NIR window (NIR-II, 1000-1700 nm) is far less exploited. The development of the first organic photothermal nanoagent (SPNI-II ) with dual-peak absorption in both NIR windows and its utilization in photothermal therapy (PTT) are reported herein. Such a nanoagent comprises a semiconducting copolymer with two distinct segments that respectively and identically absorb NIR light at 808 and 1064 nm. With the photothermal conversion efficiency of 43.4% at 1064 nm generally higher than other inorganic nanomaterials, SPNI-II enables superior deep-tissue heating at 1064 nm over that at 808 nm at their respective safety limits. Model deep-tissue cancer PTT at a tissue depth of 5 mm validates the enhanced antitumor effect of SPNI-II when shifting laser irradiation from the NIR-I to the NIR-II window. The good biodistribution and facile synthesis of SPNI-II also allow it to be doped with an NIR dye for fluorescence-imaging-guided NIR-II PTT through systemic administration. Thus, this study paves the way for the development of new polymeric nanomaterials to advance phototherapy.

Semiconducting Polymer Nanoenzymes with Photothermic Activity for Enhanced Cancer Therapy

Regulation of enzyme activity is fundamentally challenging but practically meaningful for biology and medicine. However, noninvasive remote control of enzyme activity in living systems has been rarely demonstrated and exploited for therapy. Herein, we synthesize a semiconducting polymer nanoenzyme with photothermic activity for enhanced cancer therapy. Upon near-infrared (NIR) light irradiation, the activity of the nanoenzyme can be enhanced by 3.5-fold to efficiently digest collagen in the tumor extracellular matrix (ECM), leading to enhanced nanoparticle accumulation in tumors and consequently improved photothermal therapy (PTT). This study thus provides a promising strategy to remotely regulate enzyme activity for cancer therapy.

Compact Plasmonic Blackbody for Cancer Theranosis in the Near-Infrared II Window

We have developed a class of blackbody materials, i. e., hyperbranched Au plasmonic blackbodies (AuPBs), of compact sizes (<50 nm). The AuPBs were prepared in a seedless and surfactant-free approach based on the use of mussel-inspired dopamine. Strong intraparticle plasmonic coupling among branches in close proximity leads to intense and uniform broadband absorption across 400-1350 nm. The blackbody absorption imparts the compact AuPB with a superior photothermal efficiency of >80% and closely matched photothermal activity in the first near-infrared (NIR-I) and the second near-infrared (NIR-II) spectral windows, making it a rare broadband theranostic probe for integrated photoacoustic imaging and photothermal therapy (PTT). Our comparative study, using the same probe, has demonstrated that the improved PTT outcome of NIR-II over NIR-I primarily results from its higher maximum permission exposure (MPE) rather than the deeper tissue penetration favored by longer wavelengths. The compact plasmonic broadband nanoabsorbers with tailored surface properties hold potential for a wide spectrum of light-mediated applications.

Semiconducting photothermal nanoagonist for remote-controlled specific cancer therapy

Nanomedicine have shown success in cancer therapy, but the pharmacological actions of most nanomedicine are often nonspecific to cancer cells because of utilization of the therapeutic agents that induce cell apoptosis from inner organelles. We herein report the development of semiconducting photothermal nanoagonists that can remotely and specifically initiate the apoptosis of cancer cells from cell membrane. The organic nanoagonists comprise semiconducting polymer nanoparticles (SPNs) and capsaicin (Cap) as the photothermally responsive nanocarrier and the agonist for activation of transient receptor potential cation channel subfamily V member 1 (TRPV1), respectively. Under multiple NIR laser irradiation at the time scale of seconds, the nanoagonists can repeatedly and locally release Cap to multiply activate TRPV1 channels on the cellular membrane; the cumulative effect is the overinflux of ions in mitochondria followed by the induction of cell apoptosis specifically for TRPV1-postive cancer cells. Multiple transient activation of TRPV1 channels is essential to induce such a cell death both in vitro and in vivo because both free Cap and simple Cap-encapsulated nanoparticles fail to do so. The photothermally triggered release also ensures a high local concentration of the TRPV1 agonist at tumor site, permitting specific cancer cell therapy at a low systemic administration dosage. Our study thus demonstrates the first example of ion-channel-specific and remote-controlled drug-delivery system for cancer cell therapy.

Molecular Fluorescence and Photoacoustic Imaging in the Second Near‐Infrared Optical Window Using Organic Contrast Agents

Noninvasive near‐infrared (NIR) light ranging from 650 to 1000 nm (NIR‐I) is widely employed in fundamental research and clinical applications; however, a recently discovered second NIR (NIR‐II) window from 1000 to 1700 nm exhibits even better deep‐tissue imaging capability due to reduced photon scattering, minimized tissue autofluorescence, and increased applicable power at longer wavelengths. This review focuses on recent advances of organic contrast agents developed for in vivo fluorescence and photoacoustic imaging in the NIR‐II optical window. The superiority of the NIR‐II over the NIR‐I window for molecular imaging is first discussed in detail, followed by discussion of fluorescence and photoacoustic imaging of cancer, vasculature, and the brain using organic contrast agents in the NIR‐II window. At last, challenges and perspectives of organic contrast agents for NIR‐II in vivo imaging are suggested.

Cell Membrane Coated Semiconducting Polymer Nanoparticles for Enhanced Multimodal Cancer Phototheranostics

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.