Northeast Normal University

Photodynamic immunotherapy (PDIT) represents a promising synergistic approach to enhance the efficacy of cancer immunotherapy by inducing immunogenic cell death (ICD) through the generation of reactive oxygen species (ROS). However, the anti-cancer efficacy of PDIT is limited by insufficient ROS production and highly immunosuppressive tumor microenvironments (TMEs). In this study, a multi-bioactive nanocomposite consisting of hyaluronic acid-block-poly(1-methyl-_d-tryptophan-co-_l-glutamic acid) (HA-PMTG) and tetracarboxyl porphyrin-trivalent Fe(III) metal-organic framework (MOF^TCPP-Fe) was developed for enhanced cascading PDIT. The spindle-shaped nanocomposite HA-PMTG@MOF^TCPP-Fe, measuring 188 nm in length and 80 nm in width, demonstrated efficient uptake by 4T1 cells and alleviated tumor hypoxia through the Fenton reaction. Following intravenous injection, HA-PMTG@MOF^TCPP-Fe selectively accumulated in mouse breast cancer 4T1 tumor for up to 48 h. Upon laser irradiation, photodynamic therapy (PDT) coupled with the inhibition of indoleamine-2,3-dioxygenase (IDO) by 1-MDT successfully induced ICD, resulting in a 51.57% increase in cell surface calreticulin (CRT) positivity in the HA-PMTG@MOF^TCPP-Fe group. This increase reduced immune tolerance, suppressed tumor growth, and extended the median survival of tumor-bearing mice to 120 days. Furthermore, treatment with HA-PMTG@MOF^TCPP-Fe on the primary tumor inhibited distant tumor growth through a bystander effect and prevented tumor recurrence by activating immune memory. Thus, the multi-bioactive HA-PMTG@MOF^TCPP-Fe offers an effective cascading strategy to enhance the PDIT of cancer.

Capillary electrophoresis-mass spectrometry (CE-MS) is a powerful tool for the separation and characterization of a wide range of biomolecules with the joint merits of both CE separation and MS detection; yet its potential in multiplexed microRNAs (miRNAs) analysis remains relatively underdeveloped, owing to their extremely low expression level and high family sequence homology in complex biological matrices. To address these limitations, we develop an integrated microreactor-assisted CE-MS platform that enables signal amplification and automated sample processing. Specifically, the uniquely-designed RNA-immobilized capillary microreactor (RNA-IMR) is fabricated at the inlet of a capillary and the successive CE-MS analysis is performed via the outlet of the same capillary as the electrospray ionization (ESI) source. Target miRNAs are converted into large amount of single-stranded DNAs (ssDNAs, hereafter referred to as outputDNAs) containing poly(adenine) or poly(guanine) segments with the T7 Exo mediated recycling amplification. The resultant outputDNAs are subsequently injected into the capillary, specifically recognized by the immobilized RNAs. The captured outputDNAs then undergo acid-catalyzed depurination to hydrolyze glycosidic bonds in the poly(adenine) or poly(guanine) segments, releasing free adenine (A) or guanine (G) as signaling molecules. These small nucleobases exhibit high ionization efficiency in MS due to their low molecular weight and polarity, enabling direct MS detection without labeling. The proposed RNA-IMR CE-MS integrates purification/pre-concentration, signal conversion, CE separation and MS detection with one injection, with reduced preparation time compared to RT-qPCR and improved multiplexing compared to hybridization-based methods. Using miRNA-21 and miRNA-155 as model targets, we show that the method exhibits detection limits in the low femtomolar range and specificity for multiplexing detection of miRNAs. The method is successfully applied to simultaneously detect miRNA-21 and miRNA-155 levels in MCF-7, HepG2 cancer cells and HL-7022 cells, showing its potential value in clinical applications. By bridging enzymatic signal amplification with automated CE-MS analysis, our study establishes a generalizable framework for the utilization of CE-MS as a universal method for highly sensitive miRNA assays.

Aqueous zinc-ion batteries (AZIBs) have aroused wide research enthusiasm due to their inherent safety, cost-effectiveness and sustainability advantages. However, the parasitic side reactions and rampant dendrite growth of Zn anodes seriously limit their application. In this work, a highly crystalline hydrogen-bonded organic framework (HOF-DAT) is prepared and evaluated as a protective coating for Zn anodes for the first time. The hydrogen-bonded networks as well as abundant polar groups prevent free water from contacting the Zn anode and assist Zn²⁺ de-solvation, thus significantly suppresses side reactions. Meanwhile, the ordered and stable porous structure could provide numerous channels, which ensure uniform and rapid transport/deposition for Zn²⁺, thus guiding Zn²⁺ flux and blocking interfacial corrosion. Benefiting from these advantages, the symmetric cell of HOF-DAT@Zn achieves stable plating/stripping of more than 780 h with lower polarization voltage. In addition, the HOF-DAT@Zn//NHVO full cell also delivers a higher initial discharge capacity of 355.5 mAh g^-1 at 1 A g^-1 and good reversible capacity of 248 mAh g^-1 after 200 cycles. This work offers insights for the design of HOF-based protective coating for AZIBs.