Quaternized celluloses (QCs) were homogeneously synthesized by reacting cellulose with 3-chloro-2-hydroxypropyltrimethylammonium chloride (CHPTAC) in NaOH/urea aqueous solutions. The structure and solution properties of the QCs were characterized by using elemental analysis, FTIR, (13)C NMR, SEC-LLS, viscometer, and zeta-potential measurement. The results revealed that water-soluble QCs, with a degree of substitution (DS) value of 0.20-0.63, could be obtained by adjusting the molar ratio of CHPTAC to anhydroglucose unit (AGU) of cellulose and the reaction time. The QC solutions in water displayed a typical polyelectrolyte behavior, and the intrinsic viscosity ([eta]) value determined from the Fuoss-Strauss method increased with increasing DS value. Moreover, two QC samples (DS = 0.46 and 0.63) were selected and studied as gene carriers. The results of gel retardation assay suggested that QCs could condense DNA efficiently. QCs displayed relatively lower cytotoxicity as compared with PEI, and QC/DNA complexes exhibited effective transfection compared to the naked DNA in 293T cells. The quaternized cellulose derivatives prepared in NaOH/urea aqueous solutions could be considered as promising nonviral gene carriers.

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Pyroptosis is a lytic and inflammatory form of programmed cell death and could be induced by chemotherapy drugs via caspase-3 mediation. However, the key protein gasdermin E (GSDME, translated by the DFNA5 gene) during the caspase-3-mediated pyroptosis process is absent in most tumor cells because of the hypermethylation of DFNA5 (deafness autosomal dominant 5) gene. Here, we develop a strategy of combining decitabine (DAC) with chemotherapy nanodrugs to trigger pyroptosis of tumor cells by epigenetics, further enhancing the immunological effect of chemotherapy. DAC is pre-performed with specific tumor-bearing mice for demethylation of the DFNA5 gene in tumor cells. Subsequently, a commonly used tumor-targeting nanoliposome loaded with cisplatin (LipoDDP) is used to administrate drugs for activating the caspase-3 pathway in tumor cells and trigger pyroptosis. Experiments demonstrate that the reversal of GSDME silencing in tumor cells is achieved and facilitates the occurrence of pyroptosis. According to the anti-tumor activities, anti-metastasis results, and inhibition of recurrence, this pyroptosis-based chemotherapy strategy enhances immunological effects of chemotherapy and also provides an important insight into tumor immunotherapy.

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Natural nanoparticles have been extensively studied due to their diverse properties and easy accessibility. Here, the nanoparticles extracted from cuttlefish ink (CINPs) with significant antitumor efficacy are explored. These CINPs, with spherical morphology, good dispersibility, and biocompatibility, are rich in melanin and contain a variety of amino acids and monosaccharides. Through the activation of mitogen-activated protein kinase (MAPK) signaling pathway, CINPs can efficiently reprogram tumor-associated macrophages (TAMs) from immune-suppressive M2-like phenotype to antitumor M1-like phenotype. Besides, under near-infrared (NIR) irradiation, CINPs exhibit high photothermal effect and tumor cell killing ability, which make them a potential candidate in photothermal therapy (PTT) of tumor. In vivo, CINPs can increase the proportion of M1 macrophages and foster the recruitment of cytotoxic T lymphocytes (CTLs) to tumors, leading to reduced primary tumor growth and lung metastasis. In combination with their photothermal effect, which can induce tumor-specific antigens release, CINPs could almost completely inhibit tumor growth accompanied by more active immune responses. Collectively, these CINPs described here can provide both tumor immunotherapy and PTT, implying that CINPs are promising for tumor treatment.

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Developing appropriate photothermal agents to meet complex clinical demands is an urgent challenge for photothermal therapy of tumors. Here, platinum-doped Prussian blue (PtPB) nanozymes with tunable spectral absorption, high photothermal conversion efficiency, and good antioxidative catalytic activity are developed by one-step reduction. By controlling the doping ratio, PtPB nanozymes exhibit tunable localized surface plasmon resonance (LSPR) frequency with significantly enhanced photothermal conversion efficiency and allow multiwavelength photoacoustic/infrared thermal imaging guided photothermal therapy. Experimental band gap and density functional theory calculations further reveal that the decrement of free carrier concentrations and increase in circuit paths of electron transitions co-contribute to the enhanced photothermal conversion efficiency of PtPB with tunable LSPR frequency. Benefiting from antioxidative catalytic activity, PtPB can simultaneously relieve inflammation caused by hyperthermia. Moreover, PtPB nanozymes exhibited good biosafety after intravenous injection. Our findings provide a paradigm for designing safe and efficient photothermal agents to treat complex tumor diseases.

Surface modification of nanomaterials is essential for their biomedical applications owing to their passive immune clearance and damage to reticuloendothelial systems. Recently, a cell membrane-coating technology has been proposed as an ideal approach to modify nanomaterials owing to its facile functionalized process and good biocompatibility for improving performances of synthetic nanomaterials. Here, recent advances of cell membrane-coated nanomaterials are reviewed based on the main biological functions of the cell membrane in living cells. An overview of the cell membrane is introduced to understand its functions and potential applications. Then, the applications of cell membrane-coated nanomaterials based on the functions of the cell membrane are summarized, including physical barrier with selective permeability and cellular communication via information transmission and reception processes. Finally, perspectives of biomedical applications and challenges about cell membrane-coated nanomaterials are discussed.