Polymer-DNA Carriers Co-Deliver Photosensitizer and siRNA for Light-Promoted Gene Transfection and Hypoxia-Relieved Photodynamic Therapy.

Photochemical internalization is an efficient strategy relying on photodynamic reactions to promote siRNA endosomal escape for the success of RNA-interference gene regulation, which makes gene-photodynamic combined therapy highly synergistic and efficient. However, it is still desired to explore capable carriers to improve the delivery efficiency of the immiscible siRNA and organic photosensitizers simultaneously. Herein, we employ a micellar nanostructure (PSNA) self-assembled from polymer-DNA molecular chimeras to fulfill this task. PSNA can plentifully load photosensitizers in its hydrophobic core simply by the nanoprecipitation method. Moreover, it can organize siRNA self-assembly by the densely packed DNA shell, which leads to a higher loading capacity than the typical electrostatic condensation method. The experimental results prove that this PSNA carrier can greatly facilitate siRNA escape from the endosome/lysosome and enhance transfection. Accordingly, the PSNA-administrated therapy exhibits a significantly improved anti-tumor efficacy owing to the highly efficient co-delivery capability.

Light-Harvesting Fluorescent Spherical Nucleic Acids Self-Assembled from a DNA-Grafted Conjugated Polymer for Amplified Detection of Nucleic Acids.

The ultralow concentration of nucleic acids in complex biological samples requires fluorescence probes with high specificity and sensitivity. Herein, a new kind of spherical nucleic acids (SNAs) is developed by using fluorescent π-conjugated polymers (FCPs) as a light-harvesting antenna to enhance the signal transduction of nucleic acid detection. Specifically, amphiphilic DNA-grafted FCPs are synthesized and self-assemble into FCP-SNA structures. Tuning the hydrophobicity of the graft copolymer can adjust the size and light-harvesting capability of the FCP-SNAs. We observe that more efficient signal amplification occurs in larger FCP-SNAs, as more chromophores are involved, and the energy transfer can go beyond the Förster radius. Accordingly, the optimized FCP-SNA shows an antenna effect of up to 37-fold signal amplification and the limit of detection down to 1.7 pM in microRNA detection. Consequently, the FCP-SNA is applied to amplified in situ nucleic acid detecting and imaging at the single-cell level.

Trypsin Encapsulation in the Zeolitic Imidazolate Framework for Low-Molecular Weight Protein Analysis with High Selectivity and Efficiency.

Low-molecular weight proteins (LWPs) are important sources of biological information in biomarkers, signaling molecules, and pathology. However, the separation and analysis of LWPs in complex biological samples are challenging, mainly due to their low abundance and the complex sample pretreatment procedure. Herein, trypsin modified by poly(acrylic acid) (PAA) was encapsulated by a zeolitic imidazolate framework (ZIF-L). Mesopores were formed on the ZIF-L with the introduction of PAA. An alternative strategy for separation and pretreatment of LWPs was developed based on the prepared ZIF-L-encapsulated trypsin with adjustable pore size. The mesoporous structure of the prepared materials selectively excluded high-molecular weight proteins from the reaction system, allowing LWPs to enter the pores and react with the internal trypsin, resulting in an improved separation efficiency. The hydrophobicity of the ZIF-L simplified the digestion process by inducing significant structural changes in substrate proteins. In addition, the enzymatic activity was significantly enhanced by the developed encapsulation method that maintained the enzyme conformation, allowed low mass transfer resistance, and possessed a high enzyme-to-substrate ratio. As a result, the ZIF-L-encapsulated trypsin can achieve highly selective separation, valid denaturation, and efficient digestion of LWPs in a short time by simply mixing with substrate proteins, greatly simplifying the separation and pretreatment process of the traditional hydrolysis method. The prepared materials and the developed strategy demonstrated an excellent size-selective assay performance in model protein mixtures, showing great potential in the application of proteomics analysis.