Semiconducting Polymer Nanoparticles Research Articles

Eosinophil-activating Semiconducting Polymer Nanoparticles for Cancer Photo-immunotherapy.

Eosinophils are important immune effector cells that affect T cell-mediated antitumor immunity. However, the low frequency and restrained activity of eosinophils restricted the development of cancer immunotherapies. We herein report an eosinophil-activating semiconducting polymer nanoparticle (SPNe) to improve photodynamic tumor immunogenicity, modulate eosinophil chemotaxis, and reinvigorate T-cell immunity for activated cancer photo-immunotherapy. SPNe is composed of an amphiphilic semiconducting polymer and a dipeptidyl peptidase 4 (DPP4) inhibitor sitagliptin via a 1O2-cleavable thioketal linker. Upon localized NIR photoirradiation, SPNe can generate 1O2 to elicit immunogenic cell death of tumors and induce specific activation of sitagliptin. The subsequent inhibition of DPP4 increases intratumoral CCL11 levels to promote eosinophil chemotaxis and activation. SPNe-mediated photo-immunotherapy synergized with immune checkpoint blockade greatly promotes tumor infiltration and activation of both eosinophils and T cells, effectively inhibiting tumor growth and metastasis. Thus, this study presents a generic polymeric nanoplatform to modulate specific immune cells for precision cancer immunotherapy.

Eosinophil‐activating Semiconducting Polymer Nanoparticles for Cancer Photo‐immunotherapy

Eosinophils are important immune effector cells that affect T cell‐mediated antitumor immunity. However, the low frequency and restrained activity of eosinophils restricted the development of cancer immunotherapies. We herein report an eosinophil‐activating semiconducting polymer nanoparticle (SPNe) to improve photodynamic tumor immunogenicity, modulate eosinophil chemotaxis, and reinvigorate T‐cell immunity for activated cancer photo‐immunotherapy. SPNe is composed of an amphiphilic semiconducting polymer and a dipeptidyl peptidase 4 (DPP4) inhibitor sitagliptin via a 1O2‐cleavable thioketal linker. Upon localized NIR photoirradiation, SPNe can generate 1O2 to elicit immunogenic cell death of tumors and induce specific activation of sitagliptin. The subsequent inhibition of DPP4 increases intratumoral CCL11 levels to promote eosinophil chemotaxis and activation. SPNe‐mediated photo‐immunotherapy synergized with immune checkpoint blockade greatly promotes tumor infiltration and activation of both eosinophils and T cells, effectively inhibiting tumor growth and metastasis. Thus, this study presents a generic polymeric nanoplatform to modulate specific immune cells for precision cancer immunotherapy.

Lanthanide Inorganic Nanoparticles Enhance Semiconducting Polymer Nanoparticles Afterglow Luminescence for In Vivo Afterglow/Magnetic Resonance Imaging.

Dual/multimodal imaging strategies are increasingly recognized for their potential to provide comprehensive diagnostic insights in cancer imaging by harnessing complementary data. This study presents an innovative probe that capitalizes on the synergistic benefits of afterglow luminescence and magnetic resonance imaging (MRI), effectively eliminating autofluorescence interference and delivering a superior signal-to-noise ratio. Additionally, it facilitates deep tissue penetration and enables noninvasive imaging. Despite the advantages, only a limited number of probes have demonstrated the capability to simultaneously enhance afterglow luminescence and achieve high-resolution MRI and afterglow imaging. Herein, we introduce a cutting-edge imaging platform based on semiconducting polymer nanoparticles (PFODBT) integrated with NaYF4@NaGdF4 (Y@Gd@PFO-SPNs), which can directly amplify afterglow luminescence and generate MRI and afterglow signals in tumor tissues. The proposed mechanism involves lanthanide nanoparticles producing singlet oxygen (1O2) upon white light irradiation, which subsequently oxidizes PFODBT, thereby intensifying afterglow luminescence. This innovative platform paves the way for the development of high signal-to-background ratio imaging modalities, promising noninvasive diagnostics for cancer.

Afterglow Performance of Phenylenevinylene-Based Semiconducting Polymer Nanoparticles Doped with Photosensitizers Containing Electron-Withdrawing Groups.

It is usually believed that doping with photosensitizers capable of generating singlet oxygen (1O2) plays a pivotal role in enhancing the afterglow performance of semiconducting polymer nanoparticles (SPNs). However, the effect of doping photosensitizer bearing electron-withdrawing groupshas not been reported. Here we report the effect of doping with six photosensitizers possessing different electron-withdrawing groups on the afterglow performance of SPNs using poly[(9,9-di(2-ethylhexyl)-9H-fluo-rene-2,7-vinylene)-co-(1-methoxy-4-(2-ethylhexyloxy)-2,5-phenylenevinylene)] (PF-MEHPPV) as substrate. It was found that the afterglow performance of SPNs was significantly influenced by doping with photosensitizers bearing electron-withdrawing groups. For the doped photosensitizers with strong electron-withdrawing groups, the stronger the electron-withdrawing ability of the group, the worse of the afterglow performance of the SPN regardless of the 1O2generation ability of the photosensitizer. When the doped photosensitizer exhibited weak or none electron-withdrawing effect, the 1O2 generation ability of the photosensitizer played a dominant role on the afterglow performance of the SPNs. This work deepens the understanding of the design and synthesis of SPNs with different afterglow properties.

An all-electron acceptor-based semiconducting polymer nanoprobe for in vivo high brightness NIR-II fluorescence imaging

In vivo fluorescence imaging within the second near-infrared window (NIR-II, 1000−1700 nm) has advantages of a higher spatial resolution, and deeper tissue penetration depth than that in traditional near-infrared (NIR-I, 750−950 nm). However, currently reported most of imaging materials showed very low fluorescence quantum yield. Here, we developed a new all-acceptor strategy to design and synthesize a new diketopyrrolopyrrole-based semiconducting polymer nanoparticles (PDP NPs) with high quantum yield (∼1.3 %–0.13 %) by Stille reaction of weak and moderate electron acceptor. Such high fluorescence quantum yield may be attributed to the all-acceptor strategy effectively reducing the polymeric intrachain charge-transfer effect. The fluorescence quantum yield (0.13 %) of PDP NPs was higher than currently reported most of semiconducting polymer nanoparticles. Thus, the PDP NPs-enhanced NIR-II imaging exhibited clear microvascular networks in living mice as well as xenograft 4T1 tumor with high signal-to-background ratio and spatial resolution. This study not only introduced an all-acceptor strategy to fabricate diketopyrrolopyrrole-based semiconducting polymer nanoparticles, but also provided a convenient and effective approach to amplify the effectiveness of imaging in vivo.

Rational design of biodegradable semiconducting polymer nanoparticles for NIR-II fluorescence imaging-guided photodynamic therapy

Rational design of biodegradable semiconducting polymer nanoparticles for NIR-II fluorescence imaging-guided photodynamic therapy

Leveraging Semiconducting Polymer Nanoparticles for Combination Cancer Immunotherapy.

Cancer immunotherapy has become a promising method for cancer treatment, bringing hope to advanced cancer patients. However, immune-related adverse events caused by immunotherapy also bring heavy burden to patients. Semiconducting polymer nanoparticles (SPNs) as an emerging nanomaterial with high biocompatibility, can eliminate tumors and induce tumor immunogenic cell death through different therapeutic modalities, including photothermal therapy, photodynamic therapy, and sonodynamic therapy. In addition, SPNs can work as a functional nanocarrier to synergize with a variety of immunomodulators to amplify anti-tumor immune responses. In this review, SPNs-based combination cancer immunotherapy is comprehensively summarized according to the SPNs' therapeutic modalities and the type of loaded immunomodulators. The in-depth understanding of existing SPNs-based therapeutic modalities will hopefully inspire the design of more novel nanomaterials with potent anti-tumor immune effects, and ultimately promote their clinical translation.

Sonodynamic Cytokine Nanocomplexes with Specific Stimulation towards Effector T Cell for Combination Cancer Immunotherapy

AbstractCytokine therapy mediates the interaction between immune cells and non‐immune cells in the tumor microenvironment (TME), forming a promising approach in cancer therapy. However, the dose‐dependent adverse effects and non‐selective stimulation of cytokines limit their clinical use. We herein report a sonodynamic cytokine nano‐immunocomplex (SPNAI) that specifically activates effector T cells (Teffs) for antitumor immunotherapy. By conjugating anti‐interleukin‐2 (anti‐IL‐2) antibodies S4B6 on the semiconducting polymer nanoparticles to afford SPNA, this nanoantibody SPNA can bind with IL‐2 to form SPNAI which can block the interaction between IL‐2 and regulatory T cells (Tregs), selectively activating Teffs in TME. Moreover, SPNAI generates 1O2 to trigger immunogenic cell death of cancer cells upon sono‐irradiation, which promotes the maturation of dendritic cells and the proliferation of Teffs. This SPNAI‐mediated combination sonodynamic immunotherapy thus elevates the ratio of Teffs/Tregs in TME, resulting in inhibition of tumor growth, suppression of lung metastasis and prevention of tumor relapse.

Sonodynamic Cytokine Nanocomplexes with Specific Stimulation towards Effector T cell for Combination Cancer Immunotherapy.

Cytokine therapy mediates the interaction between immune cells and non-immune cells in tumor microenvironment (TME), forming a promising approach in cancer therapy. However, the dose-dependent adverse effects and non-selective stimulation of cytokines limit their clinical use. We herein report a sonodynamic cytokine nano-immunocomplex (SPNAI) that specifically activates effector T cells (Teffs) for antitumor immunotherapy. By conjugating anti-interleukin-2 (anti-IL-2) antibodies S4B6 on the semiconducting polymer nanoparticles to afford SPNA, this nanoantibody SPNA can bind with IL-2 to form SPNAI which can block the interaction between IL-2 and regulatory T cells (Tregs), selectively activating Teffs in TME. Moreover, SPNAI generates 1O2 to trigger immunogenic cell death of cancer cells upon sono-irradiation, which promotes the maturation of dendritic cells and the proliferation of Teffs. This SPNAI-mediated combination sonodynamic immunotherapy thus elevates the ratio of Teffs/Tregs in TME, resulting in inhibition of tumor growth, suppression of lung metastasis and prevention of tumor relapse.

Activatable Semiconducting Polymer Nanoinducers Amplify Oxidative Damage via Sono-Ferroptosis for Synergistic Therapy of Bone Metastasis.

Bone metastases are secondary malignant tumors that commonly occur after the spread of advanced cancer cells. We herein report the activatable semiconducting polymer nanoinducers (ASPNFP) that can amplify oxidative damage via sono-ferroptosis for bone metastasis treatment. ASPNFP are constructed by encapsulating plasma amine oxidase-based semiconducting polymer nanoparticles (SPNP) and Fe3O4 nanoparticles into singlet oxygen (1O2)-responsive nanocarriers. ASPNFP generate 1O2 under ultrasound (US) irradiation via a sonodynamic effect to destroy the stability of 1O2-responsive nanocarriers, allowing US-triggered releases of SPNP and Fe3O4 nanoparticles. SPNP decompose polyamines in tumor cells to produce acrolein and hydrogen peroxide (H2O2), in which H2O2 promotes Fenton reaction mediated by Fe3O4 nanoparticles for inducing enhanced ferroptosis and generation of hydroxyl radicals (•OH). The generated acrolein, 1O2, and •OH can simultaneously amplify the oxidative damage. ASPNFP thus mediate an amplified sono-ferroptosis effect to inhibit the growth of bone metastasis and restrict tumor metastasis.

Dual-modulation of immunosuppressive pathways using sono-activatable semiconducting polymer nanofeedbacks for cancer immunotherapy

Although the combinations of immunotherapy with other therapies can offer promising possibility to sensitize tumors to various immunotherapeutic strategies for amplified antitumor immune responses, the up-regulations of immunosuppressive pathways after cancer treatments still greatly compromise the therapeutic outcomes. Herein, we report the dual-modulation of up-regulated immunosuppressive pathways by designing sono-activatable semiconducting polymer nanofeedbacks (SPNSA) for cancer immunotherapy. The SPNSA are constructed to contain semiconducting polymer nanoparticles (SPNs) as the sonosensitizers, adenosine receptor A2A antagonist (SCH58261), programmed death-ligand 1 (PD-L1) antibody (aPD-L1) and singlet oxygen (1O2)-cleavable linkers. Upon ultrasound (US) irradiation, the SPNs produce 1O2 for sonodynamic therapy (SDT) and inducing immunogenic cell death (ICD) with up-regulations of adenosine level and PD-L1 expression. In addition, the produced 1O2 can snip the 1O2-cleavable linkers for on-demand release of SCH58261 and aPD-L1 that act as the feedbacks to modulate the up-regulated immunosuppressive adenosine and PD-L1 pathways simultaneously, resulting in further amplified antitumor immunological effect. In the bilateral tumor-bearing mouse models, the administration of SPNSA and sono-activation can greatly inhibit the tumor growths and metastasis. This study thus provides a sono-activatable nanoplatform for precisely amplifying immunotherapeutic effect via feedback modulating of immunosuppressive pathways post-treatments.

EGFR-targeted semiconducting polymer nanoparticles for photoacoustic imaging

Semiconducting polymer nanoparticles (SPN), formulated from organic semiconducting polymers and lipids, show promise as exogenous contrast agents for photoacoustic imaging (PAI). To fully realise the potential of this class of nanoparticles for imaging and therapeutic applications, a broad range of active targeting strategies, where ligands specific to receptors on the target cells are displayed on the SPN surface, are urgently needed. In addition, effective strategies for quantifying the level of surface modification are also needed to support development of ligand-targeted SPN. In this paper, we have developed methods to prepare SPN bearing peptides targeted to Epidermal Growth Factor Receptors (EGFR), which are overexpressed at the surface of a wide variety of cancer cell types. In addition to fully characterising these targeted nanoparticles by standard methods (UV–visible, photoacoustic absorption, dynamic light scattering, zeta potential and SEM), we have developed a powerful new NMR method to determine the degree of conjugation and the number of targeting peptides attached to the SPN. Preliminary in vitro experiments with the colorectal cancer cell line LIM1215 indicated that the EGFR-targeting peptide conjugated SPN were either ineffective in delivering the SPN to the cells, or that the targeting peptide itself destabilised the formulation. This in reinforces the need for effective characterisation techniques to measure the surface accessibility of targeting ligands attached to nanoparticles.

Single-component organic semiconducting polymer nanoparticles for near-infrared afterglow imaging

Afterglow imaging holds great promise in the field of bioimaging owing to its ultrahigh imaging sensitivity. However, most reported afterglow imaging nanoprobes are prepared via nanoprecipitation, which both their stability and Förster resonance energy transfer (FRET) efficiency can further be improved. Herein, we report a single-component organic afterglow nanoprobe (PPVP-PEG) for lymph nodes and tumor imaging. PPVP-PEG is synthesized by conjugating both near-infrared (NIR) emitting photosensitizer (tetraphenylporphyrin, TPP) and poly(ethylene glycol) (PEG) onto side chains of polyphenylenevinylene (PPV). Such structure makes PPVP-PEG an amphiphilic copolymer that can self-assemble into water without the addition of stabilizer. PPVP-PEG has NIR afterglow emission and higher afterglow intensity than PPV-PEG without TPP conjugation. In addition, PPVP-PEG has a higher FRET efficiency between TPP and PPV than similar nanoprobe prepared via nanoprecipitation. The afterglow signal of PPVP-PEG can clearly detect lymph nodes of mice with high sensitivity. In addition, owing to the unique structure, PPVP-PEG shows excellent tumor targeting capability. Combining with the high sensitivity of afterglow imaging, the tumor can be imaged with high signal-to-background ratio. Thus, this work provides an approach to improve the stability and FRET efficiency of afterglow probe and may boost the development of afterglow imaging.

Continuous Preparation of Semiconducting Polymer Nanoparticles with Varied Sizes for Online Fluorescence Sensing via a Laser-Tailored 3D Microfluidic Chip.

Microfluidic chips are in critical demand for emerging applications in material synthesis and biosensing. Herein, we relied on ultrafast laser-processing technology to fabricate a three-dimensional (3D) microfluidic chip, in which semiconducting polymer nanoparticles (SPNs) were continuously synthesized with tunable size and SPN-involved online fluorescence sensing was implemented. A homogeneous distribution of SPNs can be readily realized due to the efficient mixing and powerful vortices of the 3D microfluidic chip, which prevents SPNs from aggregating throughout the synthesis process. Moreover, in the optimized conditions, we unveiled unique SPNs with an ultrasmall particle size (<3 nm) and good monodispersity. By integrating with the high-performance fluorescence of SPNs and 3D microfluidic chip, we further developed an online sensing platform for ratiometric fluorescence assays of H2O2 and oxidase-catalyzed substrates (e.g., glucose), in which a composite of SPNs and neutral red (NR) (SPNs/NR) was used as the mediator. The limit of detection (LOD) for H2O2 is 0.48 μM, and the LOD for glucose is 3.33 μM via the presented platform. This 3D microfluidic synthesis-and-sensing platform provides a new avenue for the facile production of nanoparticles and offers exciting prospects in the field of online sensing biomarkers.

Quinoxalineimide-Based Semiconducting Polymer Nanoparticles as an Effective Phototheranostic for the Second Near-Infrared Fluorescence Imaging and Photothermal Therapy.

Multifunctional theranostics play a critical role in improving the efficacy of photothermal therapy and tumor fluorescence imaging; however, they require the integration of complex components into a single theranostic system, and their response in the second near-infrared (NIR-II) region is constrained by wavelengths of a photosensitizer. To address this issue, we herein developed a novel multifunctional thiazole-fused quinoxalineimide semiconducting polymer (named PQIA-BDTT), which exhibits NIR-II fluorescence and photothermal properties. PQIA-BDTT nanoparticles achieved an impressively high photothermal conversion efficiency (72.6%) in laser (1064 nm)-induced photothermal therapy at a safe maximum permissible exposure, demonstrating their capability as an effective photothermal agent. Moreover, PQIA-BDTT nanoparticles can be used as a reference for NIR-II fluorescence imaging under a low laser fluence. The tumor size and location in 4T1 mice intravenously injected with the PQIA-BDTT nanoparticles could be precisely identified through NIR-II fluorescence imaging, which also exhibited remarkable photothermal antitumor efficacy by in vitro and in vivo therapy. Overall, this study demonstrates that introducing a thiazole-fused quinoxalineimide acceptor unit into a donor-acceptor conjugated polymer is an effective strategy for the synthesis of novel multifunctional theranostic systems, which provides a novel platform for designing theranostic agents for biomedical applications.

Optical Bioimaging and Therapy

In 1665, Britain physicist Robert Hooke first observed the plant cells upon a cork slice. Since then, scientists have never stopped pursuing more advanced technology for optical bioimaging, facilitating progress in biological and medical fields. In the 21st century, optical bioimaging has become a more important analytical tool in the research of life science and created multiple breakthroughs on the field which were awarded the Nobel Prize, such as super-resolution fluorescence microscopy (2014) and the applications of green fluorescent protein for bioimaging (2008). In recent years, along with the flourishment of nanotechnology and nanomaterials, enormous promotion on optical cancer theranostics has been produced. First published in 2013, Advanced Optical Materials is an interdisciplinary journal for top quality research in photonics, plasmonics, metamaterials, and more. Up till now, over 5,000 scientific articles have been reported in Advanced Optical Materials for their great contributions to the development of the fields in optical materials science. To celebrate the 10th anniversary of the Advanced Optical Materials publication and witness the great achievements, this special issue on “Optical Bioimaging and Therapy” includes 20 articles to highlight the recent research progresses in the flourishing field of optical bioimaging and cancer phototherapy. In recent years, the near-infrared (NIR) between 700 and 1,700 nm has been regarded as the “tissue-transparent” window in biomedical field. Till now, various advanced biomaterials have been developed for high-efficiency of NIR light energy conversion for optical bioimaging and therapy, such as down/up-conversion nanomaterials, long-lasting phosphors, semiconductor quantum dots, carbon dots and polymer (carbonized) dots, organic phosphors, etc. Even with such great success, so far, new materials are still being exploited. For example, two kinds of ytterbium dimers were prepared by the Loïc J. Charbonnière group (see article 2202307), which exhibit two-photon cooperative luminescence upconversion. Various material-decorated photosynthetic microorganisms with intrinsic oxygenation and autofluorescence have been reported for a variety of biological applications (Bengang Xing et al., see article 2203038). Apart from the innovation in material, the other key concern is surface modification of materials, which affects their colloidal dispersibility, stability and fluorescence intensity in water and physiological buffers. Hence, Haichun Liu et al. summarized the latest advances on how to adapt lanthanide-doped luminescent nanoparticles (LNPs) to an aqueous medium, ways to utilize the interaction between the LNPs and their medium, and particularly focusing on advances in nanomedicine applications (see article 2200513). Optical bioimaging can provide visualization results for many biological parameters or events, and thus possesses broad application prospects. For instance, Daniel Jaque and co-workers achieved reliable intranuclear thermal measurements by utilizing green fluorescence protein (GFP) based thermometers (see article 2201664). The Ka-Leung Wong group reported a Eu(III)-based complex as a small-molecule optical imaging agent which shows off–on luminescence and realized real-time quantitative analysis for the progress of the bioorthogonal reaction (see article 2203057). In recent years, in vivo optical imaging in the second-near-infrared window (NIR-II, 1000–1700 nm) with reduced photon scattering and autofluorescence received an increasing attention, which allows high spatiotemporal resolution and imaging depth. Niko Hildebrandt et al. prepared NIR-II-emitting ultrasmall gold nanoclusters encapsulated polymer nanoparticles to accomplish 3.8 × 106 M–1 cm–1 of brightnesses (see article 2201474). Furthermore, the themes about near-infrared windows I and II phosphors for theranostic applications (Ru-Shi Liu et al., see article 2202061) and NIR-II lanthanide luminescent nanocrystals for improved biomedical application (Fan Zhang et al., see article 2202039) are reviewed, respectively, having a significant meaning for further application of NIR-II bioimaging. Persistent luminescence also attracted a wide range of research interests, with the exception of NIR-II bioimaging. For instance, Bruno Viana et al. presented persistent luminescence at 700 nm after charging with a 980 nm laser, which helps increase rechargeability capacity as the excitation wavelength is fully inside the biological window (see article 2201468). In addition, the Piaoping Yang group highlighted the recent progress in inorganic afterglow materials, containing mechanisms, persistent luminescent properties, modulating methods, and bioimaging applications (see article 2202382). Similarly, a comprehensive overview of the recent advances in the development of semiconducting polymer nanoparticles in the NIR-II region for biomedical imaging and therapeutics are presented by Changfeng Wu and his co-workers (see article 2202052). Cancer phototherapy is a method that uses NIR light to achieve noninvasive tumor treatment and usually includes photothermal therapy (PTT), photodynamic therapy (PDT) and light controlled drug release. Due to its low energy requirements and deeper penetration of NIR light in comparison with visible light, NIR light guided cancer phototherapy possesses better biosecurity and lower tissue damage. In this special issue, 5 research articles about tumor phototherapy are prominently displayed, including bismuth-based nanoparticles (Chuanbin Mao et al., see article 2201482), manganese-silicon nanocomposite (Jun Lin et al., see article 2202022), metal-organic frameworks (Yanli Zhao et al., see article 2201043), upconversion nanoparticles (UCNPs) (Chunxia Li et al., see article 2202060) and copper peroxide nanomaterials (Ping'an Ma et al., see article 2202040). As a representative NIR light responsive nanomaterials, UCNPs can modify the NIR irradiation to visible light through a multiple-photon process, which has been widely applied in imaging, drug delivery, and antitumor therapy. Here, 3 review articles about UCNPs for biomedical applications are also recommended, such as NIR-to-ultraviolet UCNPs (Feng Wang et al., see article 2201716), heterostructures combining UCNPs and metal-organic framework (Guanying Chen et al., see article 2202122) and bacteria-targeted UCNPs (Xueyuan Chen et al., see article 2202386). Moreover, thanks to the noninvasive character, NIR light responsive materials for diagnosis and treatment of brain diseases are also summarized (Yinghui Wang et al., see article 2202888). This special issue highlights the advance in synthetic technology of high-quality optical nanomaterials for cancer theranostics. By means of the efficient energy transfer process and suitable surface modification, the bioimaging or labeling with light-triggered drug release, sensing, therapy and so on have been integrated to form multifunctional theranostic platform within one single item. These improvements are promising to exceed the cellular level and preclinical trials, further to be applied in the clinical translation. In summary, this special issue is in honor of the 10th anniversary of the Advanced Optical Materials publication which greatly promoted the development of optical nanomaterials science especially in biomedical field in last decade. In addition, we would like to express our gratitude to all authors for their supports and contributions. We also wish that all readers can derive enjoyment and inspiration from this themed issue. Jun Lin received B.S. and M.S. degrees in Jilin University, and a Ph.D. degree in Changchun Institute of Applied Chemistry (1995). His postdoctoral studies were performed at the City University of Hong Kong (1996), Institute of New Materials (Germany, 1997), Virginia Commonwealth University (USA, 1998), and University of New Orleans (USA, 1999). He has been working as a Professor at CIAC since 2000. His research interests include bulk- and nanostructured luminescent materials and multifunctional composite materials, together with their applications in display, lighting, and biomedical fields. Bengang Xing received his Ph.D. degree from Nanjing University in 2000, after which he did his postdoctoral studies in HKUST, UCLA, and Stanford University. He joined Nanyang Technological University (NTU) in 2006. Currently, he is a full professor in the School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore. His research interest is at the interfaces of bio-fluorescence imaging, chemical biology and nano-medicines, mainly focusing on the development of “smart” small molecules, peptides, and nanoprobes for biological process monitoring and diagnosis. Dayong Jin obtained his PhD from Macquarie University in 2007. At Macquarie, he was promoted to Lecturer in 2010, Senior Lecturer in 2013, Associate Professor in 2014, and Professor in 2015. He joined UTS in 2015, as a Chair Professor, and was promoted to Distinguished Professor in 2017. He established the Australian Industry Transformation Research Hub (ARC IDEAL Hub), and the UTS Institute for Biomedical Materials & Devices (IBMD), to transform advances in phonics and materials into disruptive biotechnologies. He is a Clarivate Highly Cited Researcher, a fellow of the Australian Academy of Technology and Engineering, and an ARC Laureate Fellow, with expertise covering biomedical engineering, nanotechnology, microscopy, microfluidics, and analytical chemistry, to enable rapid detection of cells and molecules.

Transferrin-Conjugated Manganese Dioxide/Semiconducting Polymer Hybrid Nanoparticles for Targeted Dual-Model Imaging of Orthotopic Glioblastoma

Glioblastoma is one of the important diseases that threaten human health, while the early diagnosis of glioblastoma remains a great challenge. We herein report the development of transferrin (Tf)-conjugated hybrid nanoparticles for targeted magnetic resonance (MR) and near-infrared (NIR) fluorescence dual-model imaging of orthotopic glioblastoma in living mouse models. Tf-stabilized manganese dioxide (MnO2) nanoparticles were conjugated onto the surface of semiconducting polymer nanoparticles (SPNs) to allow the formation of hybrid nanoparticles (Tf@SPNM). Due to the surface modification of Tf that could bind to the Tf receptor, Tf@SPNM would overcome the blood–brain barrier (BBB) and target the glioblastoma cells, which resulted in a more effective delivery of Tf@SPNM into orthotopic glioblastoma sites compared to that of their control nanoparticles. In view of the high r1 relaxation (9.8 mM–1 s–1) and bright NIR fluorescence emission, Tf@SPNM could achieve MR and NIR fluorescence dual-model imaging of orthotopic glioblastoma with obviously improved imaging contrast. Thus, this study provides a multifunctional hybrid nanoplatform for effective diagnosis of orthotopic glioblastoma.

Amplification of Cerenkov luminescence using semiconducting polymers for cancer theranostics.

The therapeutic efficacy of photodynamic therapy is limited by the ability of light to penetrate tissues. Due to this limitation, Cerenkov luminescence (CL) from radionuclides has recently been proposed as an alternative light source in a strategy referred to as Cerenkov radiation induced therapy (CRIT). Semiconducting polymer nanoparticles (SPNs) have ideal optical properties, such as large absorption cross-sections and broad absorbance, which can be utilized to harness the relatively weak CL produced by radionuclides. SPNs can be doped with photosensitizers and have nearly 100% energy transfer efficiency by multiple energy transfer mechanisms. Herein, we investigated an optimized photosensitizer doped SPN as a nanosystem to harness and amplify CL for cancer theranostics. We found that semiconducting polymers significantly amplified CL energy transfer efficiency. Bimodal PET and optical imaging studies showed high tumor uptake and retention of the optimized SPNs when administered intravenously or intratumorally. Lastly, we found that photosensitizer doped SPNs have excellent potential as a cancer theranostics nanosystem in an in vivo tumor therapy study. Our study shows that SPNs are ideally suited to harness and amplify CL for cancer theranostics, which may provide a significant advancement for CRIT that are unabated by tissue penetration limits.

Light-Driven Self-Recruitment of Biomimetic Semiconducting Polymer Nanoparticles for Precise Tumor Vascular Disruption.

Tumor vascular disrupting therapy has offered promising opportunities to treat cancer in clinical practice, whereas the overall therapeutic efficacy is notably limited due to the off-target effects and repeated dose toxicity of vascular disrupting agents (VDAs). To tackle this problem, a VDA-free biomimetic semiconducting polymer nanoparticle (SPNP ) is herein reported for precise tumor vascular disruption through two-stage light manipulation. SPNP consists of a semiconducting polymer nanoparticle as the photothermal agent camouflaged with platelet membranes that specifically target disrupted vasculature. Upon the first photoirradiation, SPNP administered in vivo generates mild hyperthermia to trigger tumor vascular hemorrhage, which activates the coagulation cascade and recruits more SPNP to injured blood vessels. Such enhanced tumor vascular targeting of photothermal agents enables intense hyperthermia to destroy the tumor vasculature during the second photoirradiation, leading to complete tumor eradication and efficient metastasis inhibition. Intriguingly, the mechanism study reveals that this vascular disruption strategy alleviates splenomegaly and reverses the immunosuppressive tumor microenvironment by reducing myeloid-derived suppressor cells. Therefore, this study not only illustrates a light-driven self-recruitment strategy to enhance tumor vascular disruption via a single dose of biomimetic therapeutics but also deciphers the immunotherapeutic role of vascular disruption therapy that is conducive to clinical studies.

Cell-Membrane Coated Nanoparticles for Tumor Delineation and Qualitative Estimation of Cancer Biomarkers at Single Wavelength Excitation in Murine and Phantom Models.

Real-time guidance through fluorescence imaging improves the surgical outcomes of tumor resections, reducing the chances of leaving positive margins behind. As tumors are heterogeneous, it is imperative to interrogate multiple overexpressed cancer biomarkers with high sensitivity and specificity to improve surgical outcomes. However, for accurate tumor delineation and ratiometric detection of tumor biomarkers, current methods require multiple excitation wavelengths to image multiple biomarkers, which is impractical in a clinical setting. Here, we have developed a biomimetic platform comprising near-infrared fluorescent semiconducting polymer nanoparticles (SPNs) with red blood cell membrane (RBC) coating, capable of targeting two representative cell-surface biomarkers (folate, αυβ3 integrins) using a single excitation wavelength for tumor delineation during surgical interventions. We evaluate our single excitation ratiometric nanoparticles in in vitro tumor cells, ex vivo tumor-mimicking phantoms, and in vivo mouse xenograft tumor models. Favorable biological properties (improved biocompatibility, prolonged blood circulation, reduced liver uptake) are complemented by superior spectral features: (i) specific fluorescence enhancement in tumor regions with high tumor-to-normal tissue (T/NT) ratios in ex vivo samples and (ii) estimation of cell-surface tumor biomarkers with single wavelength excitation providing insights about cancer progression (metastases). Our single excitation, dual output approach has the potential to differentiate between the tumor and healthy regions and simultaneously provide a qualitative indicator of cancer progression, thereby guiding surgeons in the operating room with the resection process.