Despite its growing promise in cancer treatment, ferrotherapy has low therapeutic efficacy due to compromised Fenton catalytic efficiency tumor milieu. We herein report a hybrid semiconducting nanozyme (HSN) with high photothermal conversion for photoacoustic (PA) imaging-guided second near-infrared ferrotherapy. HSN comprises an amphiphilic polymer as converter, PA emitter and iron-chelating catalyst. Upon photoirradiation, generates heat not only induce cytotoxicity but also enhance...

Abstract Nanomedicine in combination with immunotherapy offers opportunities to treat cancer a safe and effective manner; however, remote control of immune response spatiotemporal precision remains challenging. We herein report photothermally activatable polymeric pro-nanoagonist (APNA) that is specifically regulated by deep-tissue-penetrating second near-infrared (NIR-II) light for combinational photothermal immunotherapy. APNA constructed from covalent conjugation an immunostimulant onto...

Phototheranostic nanoagents are promising for early diagnosis and precision therapy of cancer. However, their imaging ability therapeutic efficacy often limited due to the presence delivery barriers in tumor microenvironment. Herein, we report development organic multimodal phototheranostic that can biomimetically target cancer-associated fibroblasts microenvironment enhanced imaging-guided cancer therapy. Such biomimetic nanocamouflages comprise a near-infrared (NIR) absorbing...

Photodynamic therapy (PDT) holds great promise for cancer therapy; however, its efficacy is often compromised by tumor hypoxia. Herein, we report the synthesis of a semiconducting polymer nanoprodrug (SPNpd) that not only efficiently generates singlet oxygen (1 O2 ) under NIR photoirradiation but also specifically activates chemotherapeutic action in hypoxic microenvironment. SPNpd self-assembled from amphiphilic brush, which comprises light-responsive photodynamic backbone grafted with...

Photoacoustic (PA) imaging in the second near-infrared (NIR-II) window (1000-1700 nm) holds great promise for deep-tissue diagnosis due to reduced light scattering and minimized tissue absorption; however, exploration of such a noninvasive technique is greatly constrained by lack biodegradable NIR-II absorbing agents. Herein, first series metabolizable PA agents are reported based on semiconducting polymer nanoparticles (SPNs). Such completely organic nanoagents consist π-conjugated yet...

Abstract Theranostics provides opportunities for precision cancer therapy. However, theranostic probes that simultaneously turn on their diagnostic signal and pharmacological action only in respond to a targeted biomarker have been less exploited. We herein report the synthesis of macrotheranostic probe specifically activates its near‐infrared fluorescence (NIRF), photoacoustic (PA), photothermal signals presence cancer‐overexpressed enzyme imaging‐guided Superior small‐molecule counterpart...

Abstract 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 off-target side effects. Proteolysis targeting chimeras (PROTACs) provide an alternative way modulate protein homeostasis for therapy; however, the always-on bioactivity existing PROTACs potentially leads uncontrollable degradation at non-target sites,...

Abstract In this study, an organic semiconducting pro‐nanostimulant (OSPS) with a near‐infrared (NIR) photoactivatable immunotherapeutic action for synergetic cancer therapy is presented. OSPS comprises polymer nanoparticle (SPN) core and immunostimulant conjugated through singlet oxygen ( 1 O 2 ) cleavable linkers. Upon NIR laser irradiation, generates both heat to exert combinational phototherapy not only ablate tumors but also produce tumor‐associated antigens. More importantly,...

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

Abstract Afterglow imaging with long-lasting luminescence after cessation of light excitation provides opportunities for ultrasensitive molecular imaging; however, the lack biologically compatible afterglow agents has impeded exploitation in clinical settings. This study presents a generic approach to transforming ordinary optical (including fluorescent polymers, dyes, and inorganic semiconductors) into luminescent nanoparticles (ALNPs). integrates cascade photoreaction single-particle...

Therapeutic enzymes hold great promise for cancer therapy; however, in vivo remote control of enzymatic activity to improve their therapeutic specificity remains challenging. This study reports the development an organic semiconducting pro-nanoenzyme (OSPE) with a photoactivatable feature metastasis-inhibited therapy. Upon near-infrared (NIR) light irradiation, this not only generates cytotoxic singlet oxygen (1O2) photodynamic therapy (PDT), but also triggers spontaneous cascade reaction...

Real-time imaging of immunoactivation is imperative for cancer immunotherapy and drug discovery; however, most existing agents possess "always-on" signals thus have poor signal correlation with immune responses. Herein, renal-clearable near-infrared (NIR) fluorescent macromolecular reporters are synthesized to specifically detect an immunoactivation-related biomarker (granzyme B) real-time evaluation immunotherapy. Composed a peptide-caged NIR signaling moiety linked hydrophilic...

Abstract Real‐time imaging of kidney function is important to assess the nephrotoxicity drugs and monitor progression renal diseases; however, it remains challenging because lack optical agents with high clearance signal‐to‐background ratio (SBR). Herein, a second near‐infrared (NIR‐II) fluorescent molecular semiconductor (CDIR2) synthesized for real‐time dysfunction in living mice. CDIR2 not only has efficiency (≈90 % injection dosage at 24 h post‐injection), but also solely undergoes...

The detection of exosomes is promising for the early diagnosis cancer. However, development suitable optical sensors remains challenging. We have developed first luminescent nanosensor multiplex differentiation cancer that bypasses real-time light excitation. sensor composed a near-infrared semiconducting polyelectrolyte (ASPN) forms complex with quencher-tagged aptamer. afterglow signal nanocomplex (ASPNC), being initially quenched, turned on in presence aptamer-targeted exosomes. Because...

Real-time multiplex imaging is imperative to biology and diagnosis but remains challenging for optical modality. Herein, a unimolecular chemo-fluoro-luminescent reporter (CFR) synthesized duplex of drug-induced hepatotoxicity (DIH), long-term medical concern. CFR simultaneously detects superoxide anion (O2•–) caspase-3 (casp3) through respective activation its independent chemiluminescence near-infrared fluorescence channels. Such crosstalk-free capability enables longitudinal measurement...

Inhibition of protein biosynthesis is a promising strategy to develop new therapeutic modalities for cancers; however, noninvasive precise regulation this cellular event in living systems has been rarely reported. In study, semiconducting polymer nanoblockader (SPNB ) developed that can inhibit intracellular synthesis upon near-infrared (NIR) photoactivation synergize with photodynamic therapy (PDT) metastasis-inhibited cancer therapy. SPNB self-assembled from an amphiphilic which grafted...

Abstract Chemiluminescence imaging is imperative for diagnostics and due to its intrinsically high sensitivity. To improve in vivo detection of biomarkers, chemiluminophores that simultaneously possess near‐infrared (NIR) emission modular structures amenable construction activatable probes are highly desired; however, these rare. Herein, we report two with record long NIR (>750 nm) via integration dicyanomethylene‐4H‐benzothiopyran or dicyanomethylene‐4H‐benzoselenopyran dioxetane unit....

Immunometabolic modulation offers new opportunities to treat cancers as it is highly associated with cancer progression and immunosuppressive microenvironment. However, traditional regimens using nonselective small-molecule immunomodulators lead the off-target adverse effects insufficient therapeutic outcomes. Herein a second near-infrared (NIR-II) photothermally activatable semiconducting polymeric nanoantagonist (ASPA) for synergistic photothermal immunometabolic therapy of reported. ASPA...

Activatable phototheranostics holds promise for precision cancer treatment owing to the "turn-on" signals and therapeutic effects. However, most activatable phototheranostic probes only possess photodynamic therapy (PDT) or photothermal (PTT), which suffer from poor efficacy due deficient cellular oxygen complex tumor microenvironment. We herein report a dual-locked probe that activates near-infrared fluorescence (NIRF) in tumor, triggers PDT response tumor-periphery biomarker, switches PTT...

Nanomedicine holds promise to enhance cancer immunotherapy; however, its potential elicit highly specific anti-tumor immunity without compromising immune tolerance has yet be fully unlocked. This study develops deep-tissue activatable sono-immunotherapy based on the discovery of a semiconducting polymer that generates sonodynamic singlet oxygen (1O2) substantially higher than other sonosensitizers. Conjugation two immunomodulators via 1O2-cleavable linkers onto this affords immunomodulatory...