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Eosinophils are important immune effector cells that affect T cell-mediated antitumor immunity. However, the low frequency and restrained activity of eosinophils restricted the outcome 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 comprises an amphiphilic semiconducting polymer and a dipeptidyl peptidase 4 (DPP4) inhibitor sitagliptin via a 1 O 2 -cleavable thioketal linker. Upon localized NIR photoirradiation, SPNe generates 1 O 2 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., (© 2024 Wiley-VCH GmbH.)

Real-time in vivo imaging of RNA can enhance the understanding of physio-pathological processes. However, most nucleic acid-based sensors have poor resistance to nucleases and limited photophysical properties, making them suboptimal for this purpose. To address this, a semiconducting polymer nanospherical nucleic acid probe (SENSE) for transcriptomic imaging of cancer immunity in living mice is developed. SENSE comprises a semiconducting polymer (SP) backbone covalently linked with recognition DNA strands, which are complemented by dye-labeled signal DNA strands. Upon detection of targeted T lymphocyte transcript (Gzmb: granzyme B), the signal strands are released, leading to a fluorescence enhancement correlated to transcript levels with superb sensitivity. The always-on fluorescence of the SP core also serves as an internal reference for tracking SENSE uptake in tumors. Thus, SENSE has the dual-signal channel that enables ratiometric imaging of Gzmb transcripts in the tumor of living mice for evaluating chemo-immunotherapy; moreover, it has demonstrated sensitivity and specificity comparable to flow cytometry and quantitative polymerase chain reaction,  yet offering a faster and simpler means of T cell detection in resected tumors. Therefore, SENSE represents a promising tool for in vivo RNA imaging., (© 2023 Wiley-VCH GmbH.)

Real-time imaging of immune systems benefits early diagnosis of disease and precision immunotherapy; however, most existing imaging probes either have "always-on" signals with poor correlation to immune responses, or rely on light excitation with limited imaging depth. In this work, an ultrasound-induced afterglow (sonoafterglow) nanoprobe is developed to specifically detect granzyme B for accurate imaging of T-cell immunoactivation in vivo. The sonoafterglow nanoprobe (Q-SNAP) consists of sonosensitizers, afterglow substrates, and quenchers. Upon ultrasound irradiation, sonosensitizers generate singlet oxygen, which converts substrates to high-energy dioxetane intermediates that slowly release energy after ultrasound cessation. Due to the proximity, energy from substrates can be transferred to quenchers, leading to afterglow quenching. Only in the presence of granzyme B, quenchers are liberated from Q-SNAP, resulting in bright afterglow emission with a limit of detection (LOD, 2.1 nm) much lower than most existing fluorescent probes. Due to the deep-tissue-penetrating ultrasound, sonoafterglow can be induced through a tissue of 4 cm thickness. Based on the correlation between sonoafterglow and granzyme B, Q-SNAP not only distinguishes autoimmune hepatitis from healthy liver as early as 4 h after probe injection, but also effectively monitors the cyclosporin-A-mediated reversal of T-cell hyperactivation. Q-SNAP thus offers the possibilities of dynamic monitoring of T-cell dysfunction and evaluation of prophylactic immunotherapy in deep-seated lesions., (© 2023 Wiley-VCH GmbH.)

Photothermal immunotherapy is a combinational cancer therapy modality, wherein the photothermal process can noninvasively ablate cancer and efficiently trigger cancer immunogenic cell death to ignite antitumor immunity. However, cancer cells can resist the cytotoxic lymphocyte-mediated antitumor effect via expressing serine protease inhibitory proteins (serpins) to deactivate proteolytic immunoproteases. Herein, we report a smart polymer nanoagonist (SPND) with second near-infrared (NIR-II) phototherapeutic ablation and tumor-specific immunoprotease granzyme B (GrB) restimulation for cancer photothermal immunotherapy. SPND has a semiconducting polymer backbone grafted with a small-molecule inhibitor of serpinB9 (Sb9i) via a glutathione (GSH)-cleavable linker. Once in the tumor, Sb9i can be specifically liberated from SPND to inhibit serpinB9, restimulating the activity of GrB to enhance cancer immunotherapy. Moreover, SPND induces photothermal therapy for direct tumor ablation and immunogenic cancer cell death (ICD) under NIR-II photoirradiation. Therefore, such a smart nanoagonist represents a way toward combination photothermal immunotherapy (PTI).

Molecular imaging via afterglow luminescence minimizes tissue autofluorescence and increases the signal-to-noise ratio. However, the induction of afterglow requires the prior irradiation of light, which is attenuated by scattering and absorption in tissue. Here we report the development of organic nanoparticles producing ultrasound-induced afterglow, and their proof-of-concept application in cancer immunotheranostics. The 'sonoafterglow' nanoparticles comprise a sonosensitizer acting as an initiator to produce singlet oxygen and subsequently activate a substrate for the emission of afterglow luminescence, which is brighter and detectable at larger tissue depths (4 cm) than previously reported light-induced afterglow. We formulated sonoafterglow nanoparticles containing a singlet-oxygen-cleavable prodrug for the immune-response modifier imiquimod that specifically turn on in the presence of the inflammation biomarker peroxynitrite, which is overproduced by tumour-associated M1-like macrophages. Systemic delivery of the nanoparticles allowed for sonoafterglow-guided treatment of mice bearing subcutaneous breast cancer tumours. The high sensitivity and depth of molecular sonoafterglow imaging may offer advantages for the real-time in vivo monitoring of physiopathological processes., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Imaging to evaluate tumor-associated neutrophils (TANs) is imperative for cancer immunotherapy but remains challenging. We herein report an activatable semiconducting polymer nanoprobe (SPCy) for near-infrared fluorescence (NIRF) and photoacoustic (PA) imaging of neutrophil elastase (NE), a biomarker of TANs. SPCy comprises a semiconducting polymer conjugated with a hemicyanine (hemi-Cy) dye caged by a NE-cleavable peptide as the side chain. After systemic administration, SPCy passively targets the tumor and reacts with NE to "uncage" the hemi-Cy, leading to enhanced NIRF and PA signals of the hemi-Cy but unchanged signals of the SP. Such NE-activated ratiometric NIRF and enhanced PA signals of SPCy correlate with the intratumoral population of TANs. Thus, this study not only presents the first TAN-specific PA probe, but also provides a general molecular design strategy for PA imaging of other immune-related biomarkers to facilitate screening of cancer immunotherapeutics., (© 2022 Wiley-VCH GmbH.)

Despite the great promises of sonodynamic therapy (SDT) in combination cancer therapy, its clinical applications are hindered by the "always-on" pharmacological activities of therapeutic agents and the lack of efficient sonosensitizers. Herein, the development of semiconducting polymers as efficient sonosensitizers and further development of sono-immunotherapeutic nanobodies (SPN Ab ) for activatable cancer sono-immunotherapy are reported. Conjugation of anti-CTLA-4 antibodies onto the polymer nanoparticles through a 1 O 2 -cleavable linker affords SPN Ab with relatively low CTLA-4 binding affinity. Upon sono-irradiation, SPN Ab generates 1 O 2 not only to elicit a sonodynamic effect to induce immunogenic cell death, but also to release anti-CTLA-4 antibodies and trigger in situ checkpoint blockade. Such a synergistic therapeutic action mediated by SPN Ab modulates the tumoricidal function of T-cell immunity by promoting the proliferation of cytotoxic T lymphocytes and depleting immunosuppressive regulatory T cells, resulting in effective tumor regression, metastasis inhibition, durable immunological memory, and prevention of relapse. Therefore, this study represents a proof-of-concept sonodynamic strategy using semiconducting polymers for precise spatiotemporal control over immunotherapy., (© 2022 Wiley-VCH GmbH.)

Optical nanoparticles are promising diagnostic tools; however, their shallow optical imaging depth and slow clearance from the body have impeded their use for in vivo disease detection. To address these limitations, we develop activatable polyfluorophore nanosensors with biomarker-triggered nanoparticle-to-molecule pharmacokinetic conversion and near-infrared fluorogenic turn-on response. Activatable polyfluorophore nanosensors can accumulate at the disease site and react with disease-associated proteases to undergo in situ enzyme-catalysed depolymerization. This disease-specific interaction liberates renal-clearable fluorogenic fragments from activatable polyfluorophore nanosensors for non-invasive longitudinal urinalysis and outperforms the gold standard blood and urine assays, providing a level of sensitivity and specificity comparable to those of invasive biopsy and flow cytometry analysis. In rodent models, activatable polyfluorophore nanosensors enable ultrasensitive detection of tumours (1.6 mm diameter) and early diagnosis of acute liver allograft rejection. We anticipate that our modular nanosensor platform may be applied for early diagnosis of a range of diseases via a simple urine test., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Immunotherapy that stimulates the body's own immune system to kill cancer cells has emerged as a promising cancer therapeutic method. However, some types of cancer exhibited a low response rate to immunotherapy, and the high risk of immune-related side effects has been aroused during immunotherapy, which greatly restrict its broad applications in cancer therapy. Phototherapy that uses external light to trigger the therapeutic process holds advantages including high selectivity and efficiency, and low side effects. Recently, it has been proven to be able to stimulate immune response in the tumor region by inducing immunogenic cell death (ICD), the process of which was termed photo-immunotherapy, dramatically improving therapeutic specificity over conventional immunotherapy in several aspects. Among numerous optical materials for photo-immunotherapy, semiconducting polymer nanoparticles (SPNs) have gained more and more attention owing to their excellent optical properties and good biocompatibility. In this review, we summarize recent developments of SPNs for immunotherapy and imaging of immunoactivation. Different therapeutic modalities triggered by SPNs including photo-immunotherapy and photo-immunometabolic therapy are first introduced. Then, applications of SPNs for real-time monitoring immunoactivation are discussed. Finally, the conclusion and future perspectives of this research field are given.

Combination photoimmunotherapy holds promise for tumor suppression; however, smart phototherapeutic agents that only activate their immune pharmaceutical action in tumors have been rarely developed. Herein, we report a semiconducting polymer (SP) nano-regulator (SPN T ) with cascading activation for combinational photodynamic cancer immunotherapy. SPN T comprises an immunoregulator (M-Trp: 1-methyltryptophan) conjugating to the side chain of the SP backbone via an apoptotic biomarker-cleavable linker. Under near-infrared photoirradiation, SPN T produces singlet oxygen to induce immunogenic apoptosis. Concurrently, an apoptotic biomarker is upregulated, which triggers the specific cleavage of M-Trp for indoleamine 2,3-dioxygenase (IDO) activity inhibition, regulatory T cells reduction and cytotoxic T lymphocytes infiltration. SPN T -mediated combination photodynamic immunotherapy thus reprograms the tumor immune microenvironment, resulting in efficient suppression of tumors, and inhibition of lung metastasis., (© 2021 Wiley-VCH GmbH.)

Cancer nanomedicine combined with immunotherapy has become a promising strategy for treating cancer in terms of safety and potency; however, precise regulation of the activation of antitumor immunity remains challenging. Herein, a smart semiconducting polymer nano-immunomodulator (SPNI), which responds to the acidic tumor microenvironment (TME), for precision photodynamic immunotherapy of cancer, is reported. The SPNI is self-assembled by a near-infrared (NIR)-absorbing semiconducting polymer and an amphipathic polymer conjugated with a Toll-like receptor 7 (TLR7) agonist via an acid-labile linker. Upon arrival at tumor site, SPNI undergoes hydrolysis and triggers an efficient liberation of TLR7 agonist in response to the acidic TME for dendritic cell activation. Moreover, SPNI exerts photodynamic effects for direct tumor eradication and immunogenic cancer cell death under NIR photoirradiation. The synergistic action of released immunogenic factors and acidic-TME-activated TLR7 agonist can serve as an in situ generated cancer vaccine to evoke strong antitumor activities. Notably, such localized immune activation boosts systemic antitumor immune responses, resulting in enhanced cytotoxic CD8 + T infiltration to inhibit tumor growth and metastasis. Thereby, this work presents a general strategy to devise prodrug of immunotherapeutics for precise regulation of cancer immunotherapy., (© 2022 Wiley-VCH GmbH.)

The clinical application of conventional chemotherapeutic agents, represented by cisplatin, is limited by severe side effects. So, it is essential to explore more safer and controlled drug delivery systems for synergistic chemotherapy. In this work, we designed dual-sensitive dual-prodrug nanoparticles (DDNPs) for photoactivated platinum-based synergistic chemotherapy. With photosensitivity, DDNPs could be photoactivated from inert Pt(IV) to toxic Pt(II) under safe UVA light in a spatiotemporally controlled manner. Concurrently, mild could be generated from DDNPs to assist the endo/lysosomal escape of DDNPs for better photoactivated chemotherapy (PACT). Furthermore, with acid-sensitivity, demethylcantharidin (DMC), a protein phosphatase 2A (PP2A) inhibitor, was released to block the DNA repair pathway and thereby could sensitize platinum-based chemotherapy in intracellular acidic microenvironments. Along with a precise ratio (Pt : DMC = 1 : 2), DDNPs had a powerful synergistic anti-cancer effect in vitro and in vivo . In the future, DDNPs have great potential as a safe and multifunctional drug delivery system for precise nanomedicine in clinical treatments.

Stimuli-responsive nanosystems have been widely applied as effective modalities for drug/gene co-delivery in cancer treatment. However, precise spatiotemporal manipulations of drug/gene co-delivery, as well as multi-modality imaging-guided cancer therapy, still remain a daunting challenge. Here, multifunctional polyprodrug/siRNA loaded upconversion nanoparticles (UCNPs) are reported that combine computed tomography (CT), magnetic resonance (MR), and upconversion luminescence (UCL) tri-modality imaging and near-infrared (NIR) light-activated drug/gene on-demand delivery. The photoactivatable platinum(IV) (Pt(IV))-backbone polymers (PPt) and the siRNA targeting polo-like kinase 1 (Plk1) are loaded on the surface of polyethyleneimine (PEI)-coated UCNPs (PUCNP) to obtain the multifunctional polyprodrug/siRNA loaded UCNPs (PUCNP@Pt@siPlk1). The PUCNP@Pt@siPlk1 can be served as a "nanotransducer" to convert NIR light (980 nm) into local ultraviolet (UV) to visible light for the cleavage of photosensitive PPt, resulting in the simultaneous on-demand release of high toxic platinum(II) (Pt(II)) and siPlk1. Meanwhile, the PUCNP@Pt@siPlk1 has CT, T 1 -weighted MR, and UCL tri-modality imaging abilities. Based on these merits, PUCNP@Pt@siPlk1 displayed excellent synergistic therapeutic efficacy via image-guided and NIR light-activated platinum-based chemotherapy and RNA interfering in vitro and in vivo. Thus, this developed nanosystem with NIR light-controlled drug/gene delivery and multi-modality imaging abilities, will display great potential in combining chemotherapy and gene therapy., (© 2021 Wiley-VCH GmbH.)

Nanomedicine can regulate the balance between cytotoxic T lymphocytes (CTLs) and suppressive regulatory T lymphocytes (Tregs), which however has been rarely exploited for cancer immunotherapy. We report a charge-reversal polymer nano-modulator (SP DMC N) activated by tumor microenvironment (TME) for photodynamic immunotherapy of cancer. SP DMC N is constructed by conjugating an immunomodulator (demethylcantharidin, DMC) to the side chains of a photodynamic polymer via an acid-liable linker. The negative charge of SP DMC N ensures its high stability in blood circulation and ideal tumor accumulation; exposure to acidic TME reverses its surface charge to positive, enhancing tumor penetration and locally releasing DMC. Upon near-infrared photoirradiation, SP DMC N generates singlet oxygen to ablate tumors and promote maturation of dendritic cells. Released DMC inhibits protein phosphatase 2 (PP2A) activity and decreases Tregs differentiation. Such combinational action induces a sharp increase in CTL/Treg ratio in TME and effectively inhibits both primary and distant tumors in living mice., (© 2021 Wiley-VCH GmbH.)

Despite the promise of sonodynamic processes in cancer therapy, existing sonosensitizers often fail to regulate the generation of reactive oxygen species (ROS) against tumors, potentially leading to off-target toxicity to normal tissues. We report a transformable core-shell nanosonosensitizer (TiO 2 @CaP) that reinvigorates ROS generation and dissolves its CaP shell to release Ca 2+ in an acidic tumor microenvironment (TME) under ultrasound activation. Thus, TiO 2 @CaP acts as a smart nanosonosensitizer that specifically induces mitochondrial dysfunction via overloading intracellular Ca 2+ ions to synergize with the sonodynamic process in the TME. TiO 2 @CaP substantially enhances immunogenic cell death, resulting in enhanced T-cell recruitment and infiltration into the immunogenic cold tumor (4T1). In conjunction with checkpoint blockade therapy (anti-PD 1), TiO 2 @CaP-mediated sonodynamic therapy elicits systemic antitumor immunity, leading to regression of non-treated distant tumors and inhibition of lung metastasis. This work paves the way to development of "smart" TME-activatable sonosensitizers with temporospatial control over antitumor responses., (© 2021 Wiley-VCH GmbH.)

Immunometabolic intervention has been applied to treat cancer via inhibition of certain enzymes associated with intratumoral metabolism. However, small-molecule inhibitors and genetic modification often suffer from insufficiency and off-target side effects. Proteolysis targeting chimeras (PROTACs) provide an alternative way to modulate protein homeostasis for cancer therapy; however, the always-on bioactivity of existing PROTACs potentially leads to uncontrollable protein degradation at non-target sites, limiting their in vivo therapeutic efficacy. We herein report a semiconducting polymer nano-PROTAC (SPN pro ) with phototherapeutic and activatable protein degradation abilities for photo-immunometabolic cancer therapy. SPN pro can remotely generate singlet oxygen ( 1 O 2 ) under NIR photoirradiation to eradicate tumor cells and induce immunogenic cell death (ICD) to enhance tumor immunogenicity. Moreover, the PROTAC function of SPN pro is specifically activated by a cancer biomarker (cathepsin B) to trigger targeted proteolysis of immunosuppressive indoleamine 2,3-dioxygenase (IDO) in the tumor of living mice. The persistent IDO degradation blocks tryptophan (Trp)-catabolism program and promotes the activation of effector T cells. Such a SPNpro-mediated in-situ immunometabolic intervention synergizes immunogenic phototherapy to boost the antitumor T-cell immunity, effectively inhibiting tumor growth and metastasis. Thus, this study provides a polymer platform to advance PROTAC in cancer therapy.

Development of real-time non-invasive imaging probes to assess infiltration and activation of cytotoxic T cells (CTLs) is critical to predict the efficacy of cancer immunotherapy, which however remains challenging. Reported here is an activatable semiconducting polymer nanoprobe (SPNP) for near-infrared fluorescence (NIRF) and photoacoustic (PA) imaging of a biomarker (granzyme B) associated with activation of CTLs. SPNP comprises a semiconducting polymer (SP) conjugated with a granzyme B cleavable and dye-labeled peptide as the side chain, both of which emit NIRF and PA signals. After systemic administration, SPNP passively targets the tumor and in situ reacts with granzyme B to release the dye-labeled peptide, leading to decreased NIRF and PA signals from the dye but unchanged signals from the polymer. Such ratiometric NIRF and PA signals of SPNP correlate well with the expression level of granzyme B and intratumoral population of CTLs. Thus, this study not only presents the first PA probes for in vivo imaging of immune activation but also provides a molecular design strategy that can be generalized for molecular imaging of other immune-related biomarkers., (© 2020 Wiley-VCH GmbH.)

Disability and even death from acute thrombosis remain a grave menace to public health. At present, the traditional drugs represented by urokinase (UK) in clinical thrombolysis can cause side effects of bleeding when the dosage is excess. Therefore, a more effective and safer method of thrombolysis is urgently needed. In this paper, a multifunctional dual-drug sequential release thrombolysis platform (UK-UH@PDA@HMSNs) consisting of polydopamine (PDA)-modified hollow mesoporous silicon (HMSNs) loading with UK and unfractionated heparin (UH) was constructed with a double physical assistance (NIR-II and bubbles). With the aid of near infrared-II (NIR-II, 1064 nm, 1.0 W cm -2 ) laser, the photothermal effect of PDA could be motivated to facilitate the UH release, thereby accelerating the dissolution of thrombus. Afterward, the local hyperthermia effect could expedite the phase transition of l-menthol in HMSNs to generate bubbles to promote the release of UK, thereby realizing the sequential release of two thrombolytic drugs. Importantly, this method deftly conquered the inherent obstacle that UK and UH cannot be combined directly. In vivo and in vitro experiments proved that the thrombolytic efficiency of UK-UH@PDA@HMSNs stimulated by NIR-II was nearly 3 times than that of UK alone. Collectively, the proposed dual physical assistance and sequential dual-drug delivery system significantly improved the efficiency of thrombolysis under the premise of limiting drug doses; the risk of death from intracranial hemorrhage thus could be decreased radically.

This study reports the development of iron-chelated semiconducting polycomplex nanoparticles (SPFeN) for photoacoustic (PA) imaging-guided photothermal ferrotherapy of cancer. The hybrid polymeric nanoagent comprises a ferroptosis initiator (Fe 3+ ) and an amphiphilic semiconducting polycomplex (SP C ) serving as both the photothermal nanotransducer and iron ion chelator. By virtue of poly(ethylene glycol) (PEG) grafting and its small size, SPFeN accumulates in the tumor of living mice after systemic administration, which can be monitored by PA imaging. In the acidic tumor microenvironment, SPFeN generates hydroxyl radicals, leading to ferroptosis; meanwhile, under NIR laser irradiation, it generates localized heat to not only accelerate the Fenton reaction but also implement photothermal therapy. Such a combined photothermal ferrotherapeutic effect of SPFeN leads to minimized dosage of iron compared to previous studies and effectively inhibits the tumor growth in living mice, which is not possible for the controls., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Combination of chemotherapy and gene therapy provides an effective strategy for cancer treatment. However, the lack of suitable codelivery systems with efficient endo/lysosomal escape and controllable drug release/gene unpacking is the major bottleneck for maximizing the combinational therapeutic efficacy. In this work, we developed a photoactivatable Pt(IV) prodrug-backboned polymeric nanoparticle system (CNP PtCP/si(c-fos) ) for light-controlled si(c-fos) delivery and synergistic photoactivated chemotherapy (PACT) and RNA interference (RNAi) on platinum-resistant ovarian cancer (PROC). Upon blue-light irradiation (430 nm), CNP PtCP/si(c-fos) generates oxygen-independent N 3 • with mild oxidation energy for efficient endo/lysosomal escape through N 3 • -assisted photochemical internalization with less gene deactivation. Thereafter, along with Pt(IV) prodrug activation, CNP PtCP/si(c-fos) dissociates to release active Pt(II) and unpack si(c-fos) simultaneously. Both in vitro and in vivo results demonstrated that CNP PtCP/si(c-fos) displayed excellent synergistic therapeutic efficacy on PROC with low toxicity. This PACT prodrug-backboned polymeric nanoplatform may provide a promising gene/drug codelivery tactic for treatment of various hard-to-tackle cancers.

Cancer theranostics holds potential promise for precision medicine; however, most existing theranostic nanoagents are simply developed by doping both therapeutic agents and imaging agent into one particle entity, and thus have an "always-on" pharmaceutical effect and imaging signals regardless of their in vivo location. Herein, the development of an organic afterglow protheranostic nanoassembly (APtN) that specifically activates both the pharmaceutical effect and diagnostic signals in response to a tumor-associated chemical mediator (hydrogen peroxide, H 2 O 2 ) is reported. APtN comprises an amphiphilic macromolecule and a near-infrared (NIR) dye acting as the H 2 O 2 -responsive afterglow prodrug and the afterglow initiator, respectively. Such a molecular architecture allows APtN to passively target tumors in living mice, specifically release the anticancer drug in the tumor, and spontaneously generate the uncaged afterglow substrate. Upon NIR light preirradiation, the afterglow initiator generates singlet oxygen to react and subsequently transform the uncaged afterglow substrate into an active self-luminescent form. Thus, the intensity of generated afterglow luminescence is correlated with the drug release status, permitting real-time in vivo monitoring of prodrug activation. This study proposes a background-free design strategy toward activatable cancer theranostics., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Nanocarriers based on natural biomaterials such as peptides and proteins have shown great advantages in the field of nanomedicine. However, the complicated preparation process and possible denaturation of proteins may limit their further applications. Herein, a novel method is developed to prepare protein nanocluster drug delivery system based on the self-aggregated property of proteins under the isoelectric point condition. The crosslinked protein nanoclusters, prepared by adding modified natural crosslinking agent polysaccharide, exhibit excellent stability and autofluorescent property in physiological conditions. Hemoglobin, a model protein, is chosen for preparation of drug-loaded nanoclusters. The as-prepared nanoclusters demonstrate a pH-responsive drug release behavior and can successfully deliver drugs into cancer cells. Moreover, this approach can be extended to various proteins, exemplifying the universal applicability of our new preparation method for protein-based nanoparticles., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Photoactivated therapy has become a complementary and attractive modality for traditional cancer treatment. Herein, we demonstrated a novel single-stimulus dual-drug sensitive nanoplatform, Cur-loaded Dex-Pt(N3) nanoparticles (Cur@DPNs) for enhanced photoactivated therapy. The developed Cur@DPNs could be photoactivated by UVA light to simultaneously generate instant reactive oxygen species from Cur for fast photodynamic therapy and release lasting Pt(II) from Pt(N3) for long-acting photochemotherapy. Compared with small free drugs and individual photoactivated therapy, Cur@DPNs exhibited enhanced photoactivated cytotoxicity and in vivo antitumor efficacy with low systemic toxicity accompanied. Therefore, the single-stimulus dual-drug sensitive nanoplatform is convinced to be a promising strategy for multidrug delivery, site-selective and combinational photoactivated therapy in the near future.

Development of real‐time non‐invasive imaging probes to assess infiltration and activation of cytotoxic T cells (CTLs) is critical to predict the efficacy of cancer immunotherapy, which however remains challenging. Reported here is an activatable semiconducting polymer nanoprobe (SPNP) for near‐infrared fluorescence (NIRF) and photoacoustic (PA) imaging of a biomarker (granzyme B) associated with activation of CTLs. SPNP comprises a semiconducting polymer (SP) conjugated with a granzyme B cleavable and dye‐labeled peptide as the side chain, both of which emit NIRF and PA signals. After systemic administration, SPNP passively targets the tumor and in situ reacts with granzyme B to release the dye‐labeled peptide, leading to decreased NIRF and PA signals from the dye but unchanged signals from the polymer. Such ratiometric NIRF and PA signals of SPNP correlate well with the expression level of granzyme B and intratumoral population of CTLs. Thus, this study not only presents the first PA probes for in vivo imaging of immune activation but also provides a molecular design strategy that can be generalized for molecular imaging of other immune‐related biomarkers. [ABSTRACT FROM AUTHOR]

A type of TiO 2 /WO 3 -coated magnetic nanoparticles was prepared as catalyst for photodegradation of sixteen organic dyes. The catalyst was characterized by Fourier transform infrared spectroscopy, transmission electron microscopy, X-ray diffraction, vibrating sample magnetometer, and zeta potential analysis. The tested dyes included seven reactive dyes, one metal-complex dye, two base dyes, two direct dyes, and four acidic azo dyes. The photodegradation test showed that, in the presence of catalyst, the degradation rates of dyes were relative to both their chemical structures and adsorption ability. The dyes containing chlorotriazinyl/carbamide group and showing high adsorption ability can be degraded more easily. Most of the tested dyes were degraded rapidly by catalyst under a simulated visible light. Moreover, all the dyes were completely decolorized and satisfactorily mineralized under direct irradiation of solar light. Furthermore, the randomly-chosen ten dyes were completely decolorized and satisfactorily mineralized in a short time of 77–275 min under a focused solar light. In addition, the catalyst can be easily recycled by a magnet with a good reusability. The new catalyst can be potentially utilized as a universal catalyst for degradation of different kind of dyes in water using solar light as an environmentally friendly and low-cost energy resource. [ABSTRACT FROM AUTHOR]