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Although immunotherapy has merged as an ideal cancer therapeutic strategy for preventing tumor growth and recurrence, effective approaches to treat immunologically cold tumors are still lacking. Herein, we reported a practical and extendable nanoplatform (HA/ZIF-8@ICG@IMQ) that facilely integrated various therapeutics and functions for boosting host antitumor immunity to treat immunologically cold tumors. The tumor-targeted and microenvironment-responsive HA/ZIF-8@ICG@IMQ facilitated the tumor-specific accumulation and release of photothermal agents and immune adjuvants. With near-infrared irradiation, the designed nanoparticles effectively enhanced the infiltration of cytotoxic T lymphocytes and helper T cells and effectively blocked the growth of primary and distant tumors. Moreover, the smart therapeutic could effectively prevent tumor rechallenge and recurrence with a long-term host immunological memory response. This method shows an effective immunologically cold tumor treatment using extendable nanotherapeutics and may have reference significance for clinical cancer therapy.

Unmethylated cytosine-phosphate-guanosine (CpG) oligodeoxynucleotides are immunostimulatory nucleic acids wildly utilized as adjuvants or for vaccines to treat diseases. However, there is a lack of simple and efficient vectors for CpG oligodeoxynucleotide delivery with long-lasting immune stimulation. Herein, self-assembled polymer wires consisting of CpG motifs by hybridization chain reaction were constructed with excellent biocompatibility and immunostimulatory activity. The designed polymer DNA wires acted as programmable multivalent immunoadjuvants and triggered immune response, stimulated pro-inflammatory cytokine secretion, and induced the apoptosis of cancer cells. More strikingly, polymer nanospheres assembled from the polymer DNA wires and cationic poly-l-lysine further improved cellular uptake and continuously stimulate the lysosomal Toll-like receptor 9 of immune cells, thereby remarkably enhancing the activation of immune cells. These results demonstrated that self-assembled polymer DNA nanoassemblies with multivalent CpG could trigger strong immune response and further induce cancer cell death.

Nanomaterials are commonly utilized for amplified immunoassay of biomarkers. However, traditional nanomaterial-based immunoassay usually requires a time-consuming and labor-intensive nanoparticle modification and conjugation process, which impedes their practical applications. Here, a new immunoassay method based on biosynthesized nanomaterials is developed with versatile functions for facile and ultrasensitive detection of cancer biomarker. In this method, the utilized biosynthesized quantum dots (BQDs) allow convenient antibody conjugation and electrode modification, and demonstrate excellent electrochemical and electrochemiluminescent responses. The differential pulse voltammetric, faradaic impedance spectroscopy, and electrochemiluminescent measurements with the BQD-modified electrode show detection limits at picomolar levels as well as good specificity toward human prostate-specific antigen detection. The inherent recognization capability as well as the inherent electrochemical and electrochemiluminescence features thus enable BQDs as good candidates for facile immunosensors with high sensitivity. Such a biosynthesized nanomaterial-based approach opens up the possibility of using innovative designs for nanoparticle-based assays, and developing reliable and practical methods for early disease diagnosis.

Isothermal enzyme-free nucleic acid circuits have been developed for carrying out diverse functions ranging from dictate biocomputing to amplified biosensing. Catalytic hairpin assembly (CHA), the catalyzed cross-opening of two hairpin substrates by an initiator, has attracted increasing attention because of its facile design and high amplification capacity. The complex labeling and frequent photobleaching of a conventional fluorescent CHA biosensor still remains a challenge that needs to be solved. Herein, we constructed a new label-free and enzyme-free isothermal CHA lighting up AgNCs strategy for amplified nucleic acid assay by integrating the interfacially and spatially sensitive feature of DNA-templated fluorescent silver nanoclusters (DNA-AgNCs) and the high signal amplification capability of the CHA circuit. In this strategy, one polyguanine-grafted hairpin and the other AgNCs-capturing hairpin were engineered as assembly constitutes, which were kinetically impeded from cross-hybridizations without target. However, in the presence of target, the CHA-catalyzed assembly of two functional hairpins was successively progressed and concomitantly accompanied by an efficient accommodation of AgNCs to the polyguanine-elongated dsDNA product, leading to highly efficient AgNCs-lighting up and to the generation of an amplified fluorescence signal. As a simple mix-and-detect strategy, the isothermal enzyme-free CHA-mediated lighting up AgNCs (CHA-AgNCs) system provided a facile visualization way for amplified detection of DNA with a detection limit of 20 pM, which was comparable to or even better than some enzyme-involved amplification methods. The homogeneous CHA-AgNCs system can be used as a general sensing platform and be easily adapted for analyzing other biologically important analytes, for example, microRNA (miRNA), by introducing the sensing module consisting of an auxiliary hairpin through an easy-to-integrate procedure. By taking advantage of the signal amplification features of CHA and the robust AgNCs-lighting up procedure, we anticipate that the CHA-lighting up AgNCs system can provide an important tool for biomedicine and bioimaging applications and thus should hold great promise in clinical diagnoses and treatment fields.

High mortality and rapid development of metastasis requires the development of more effective antimetastasis strategies. However, conventional therapeutic methods, including surgery, radiation therapy, and chemotherapy, show less effectiveness in curbing the metastatic spread of cancer cells and the formation of metastases. A therapeutic platform, targeting the early stage of metastasis cascade, could effectively prevent metastasis dissemination. Herein, Fe/Mn-based metal–organic frameworks (FMM) were constructed for the delivery of a specific DNAzyme with high catalytic cleavage activity on the metastasis-involved Twist mRNA, thus efficiently inhibiting the invasion of cancer cells through DNAzyme-catalyzed gene silencing. Highly potent combined gene/chemodynamic therapy is achieved from the self-supplied DNAzyme cofactors and efficient glutathione depletion. Importantly, by virtue of the intrinsic photo-to-thermal conversion of the FMM nanocarriers, our combined therapeutic strategy could be further promoted under photothermal stimuli to speed up the Fenton reaction and to accelerate the release of the Twist DNAzyme with efficient gene therapy. Consequently, the effective elimination of tumors and the blockage of metastasis are simultaneously achieved under photothermal/magnetic resonance imaging guidance. This work aims at developing versatile theranostic agents to combat metastatic tumors.