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Despite the great achievements of immune checkpoint blockade (ICB) therapy on programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) axis, ICB monotherapy still faces obstacles in eradicating solid tumors due to the lack of tumor-associated antigens or tumor-specific cytotoxicity. Photothermal therapy (PTT) is a potential therapeutic modality because it can noninvasively kill tumor cells by thermal ablation and generate both tumor-specific cytotoxicity and immunogenicity, which holds great feasibility to improve the efficiency of ICB by providing complementary immunomodulation. Except for the PD-1/PD-L1 axis, the cluster of differentiation 47 (CD47)/signal regulatory protein alpha (SIRPα) pathway has been considered as a novel strategy of tumor cells to evade the surveillance of macrophages and inactivate the immune response of PD-L1 blockade therapy. Therefore, it is necessary to synergize the antitumor effect of dual-targeting PD-L1 and CD47. Although promising, the application of PD-L1/CD47 bispecific antibodies, especially in combination with PTT, remains a formidable problem, due to the low objective response, activity loss at relatively high temperature, or nonvisualization. Herein, instead of using antibodies, we use MK-8628 (MK) to down-regulate both PD-L1 and CD47 simultaneously through halting the active transcription of oncogene c-MYC, leading to elicitation of the immune response. The hollow polydopamine (HPDA) nanospheres are introduced as a biocompatible nanoplatform with high loading capacity and magnetic resonance imaging (MRI) ability to deliver MK and induce PTT (HPDA@MK). Compared to preinjection, HPDA@MK exhibits the strongest MRI signal at 6 h postintravenous injection to guide the precise combined treatment time. However, due to the local delivery and controlled release of inhibitors, HPDA@MK down-regulates c-MYC/PD-L1/CD47, promotes the activation and recruitment of cytotoxic T cells, regulates the M2 macrophages polarization in tumor sites, and especially boosts the combined therapeutic efficacy. Collectively, our work presents a simple but distinctive approach for c-MYC/PD-L1/CD47-targeted immunotherapy combined with PTT that may provide a desirable and feasible strategy for the treatment of other clinical solid tumors.

In clinical practice, it has become urgent to develop multifunctional wound dressings that can combat infection and prompt wound healing simultaneously. In this study, we proposed a polydopamine/alginate/nanoselenium composite hydrogel (Alg-PDA-Se) for the treatment of infected wounds. In particular, polydopamine endows the composite hydrogel with controllable near-infrared photothermal properties, while low-dosage selenium nanoparticles (Se NPs) offer excellent anti-oxidation, anti-inflammatory, pro-proliferative, pro-migration, and pro-angiogenic performances, which are verified by multiple cells, including macrophages, fibroblasts, and endothelial cells. More interestingly, the combination of mild temperature with low-dosage Se NPs produces a synergistic effect on combating both Staphylococcus aureus ( S. aureus ) and Escherichia coli ( E. coli ) and promoting the healing of bacteria-infected wounds in vivo. We anticipate that the designed composite hydrogel might be a potential candidate for anti-infection bioactive dressing.

Colitis-associated colorectal cancer (CAC), in which chronic inflammation is a well-recognized carcinogen, requires concurrent anti-inflammation and antitumor treatments in the clinic. Herein, we report polyethylene glycol (PEG)-coated (PEGylated) ultrasmall rhodium nanodots (Rh-PEG NDs) can serve as a metallic nanozyme with reactive oxygen and nitrogen species (RONS) scavenging properties as well as photothermal activities for anti-inflammation and antitumor theranostics in colon diseases. Benefiting from multienzyme activities against RONS, Rh-PEG NDs can decrease the levels of pro-inflammatory cytokines (TNF-α, IL-6), resulting in good anti-inflammatory effect on dextran sulfate sodium-induced colitis. By virtue of high photothermal conversion efficiency (48.9%), Rh-PEG NDs demonstrate complete ablation of CT-26 colon tumor without any recurrence. Most importantly, Rh-PEG NDs exhibit good biocompatibility both at the cellular and animal levels. Our findings provide a paradigm to utilize metallic nanozymes for the potential management of colon diseases.

Nanochannel/nanopre based analysis methods have attracted increasing interest in recent years due to their exquisite ability to reveal changes in molecular volume. In this work, a highly asymmetric nanochannel-ionchannel hybrid coupled with an electrochemical technique was developed for copper ion (Cu 2+ ) detection. Polyglutamic acid (PGA) was modified in a nanochannel array of porous anodic alumina (PAA). When different concentrations of Cu 2+ were introduced into the nanochannel-ionchannel hybrid in a neutral environment, a Cu 2+ -PGA chelation reaction occurs, resulting in varied current-potential (I-V) properties of the nanochannel-ionchannel hybrid. When PAA was immersed in a low pH solution, the Cu 2+ -PGA complex dissociated. On the basis of the change in ionic current, a label-free assay for Cu 2+ was achieved along with the ability to regenerate and reuse the constructed platform. Because of the unique mass transfer property of the nanochannel-ionchannel hybrid combined with the highly amplified ionic current magnitude of the nanochannel array, significantly increased assay sensitivity was achieved, as expected. To evaluate the applicability of the present methodology for detecting Cu 2+ in a real sample, the Cu 2+ content in real blood samples was analyzed. The results demonstrate that the present method shows excellent selectivity with high sensitivity toward Cu 2+ detection in real blood samples.