Ionizable drug delivery systems for efficient and selective gene therapy.

Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function. However, a great challenge in bringing the nucleic acid formulations to the market is the safe and effective delivery to the specific tissues and cells. To be excited, the development of ionizable drug delivery systems (IDDSs) has promoted a great breakthrough as evidenced by the approval of the BNT162b2 vaccine for prevention of coronavirus disease 2019 (COVID-19) in 2021. Compared with conventional cationic gene vectors, IDDSs can decrease the toxicity of carriers to cell membranes, and increase cellular uptake and endosomal escape of nucleic acids by their unique pH-responsive structures. Despite the progress, there remain necessary requirements for designing more efficient IDDSs for precise gene therapy. Herein, we systematically classify the IDDSs and summarize the characteristics and advantages of IDDSs in order to explore the underlying design mechanisms. The delivery mechanisms and therapeutic applications of IDDSs are comprehensively reviewed for the delivery of pDNA and four kinds of RNA. In particular, organ selecting considerations and high-throughput screening are highlighted to explore efficiently multifunctional ionizable nanomaterials with superior gene delivery capacity. We anticipate providing references for researchers to rationally design more efficient and accurate targeted gene delivery systems in the future, and indicate ideas for developing next generation gene vectors.

Synthesis and photoluminescent properties of NaYF4:Eu3+ core and NaYF4:Eu3+/NaYF4 core/shell nanocrystals.

NaYF4:Eu3+ core and NaYF4:Eu3+/NaYF4 core/shell nanocrystals (NCs) were synthesized via a wet chemical method. The transmission electron microscope photographs show that the core and core/shell nanoparticles are monodisperse and uniform NCs with average diameters of 22 and 26 nm respectively. The photoluminescence (PL) properties of the samples, including the PL excitation and emission spectra, and luminescent decay curves, are investigated in detail. The results show that the intensity of 5D2 emission relative to that of 5D0 is stronger in NaYF4:Eu3+/NaYF4 core/shell NCs than that in NaYF4:Eu3+ core NCs, and a longer decay lifetime of 5D2 is observed in core/shell samples. In addition, from the corrected emission spectra of 5D0, the 5D0 radiative lifetimes were calculated. These together with the measured decay lifetime of 5D0 emission give the intrinsic quantum yields of 5D0. The results were well interpreted by considering the surface effects.

[Preparation and luminescence of down-conversion material beta--NaYF4 : Tb3+, Yb3+].

NaYF4 : Tb3+, Yb3+ down-conversion (DC) phosphors were synthesized by hydrothermal method. X-ray diffraction (XRD), photoluminescence (PL) and photoluminescence excitation (PLE) spectra were used to characterize the samples. Experiment results revealed that samples of NaYF4 : Tb3+, Yb3+ crystallized in hexagonal shape without cubic shape. When the doping concentration of Tb3+ and Yb3+ was altered, the lattice structure of samples did not change, indicating that the Tb3+ and Yb3+ ions are completely dissolved in the NaYF4 host lattice by substitution for the Y3+. The emission from 5D4 --> 7F6 (489 nm), 5D4 --> 7F5 (542 nm), 5D4 --> F4 (584 nm), and 5D4 --> F3 (619 nm) of Tb3+ ions was observed, in which the dominant emission was at 542 nm. With single Tb3+ doping, no near-infrared (NIR) emission was observed under excitation of 355 nm pulsed laser. However, while with Tb3+ and Yb3+ codoping, the NIR emission at around 950 -1 100 nm from Yb3+ (2F5/2 --> 2F7/2) was observed under the same excitation. The dependence of the visible and NIR-emissions on Yb3+ doping concentration has been investigated. These results show that there is energy transfer process between Tb2+ and Yb3+. Furthermore, it is a possible DC process through cooperative energy transfer from Tb3+ to Yb3+. When the doping concentration is 1% mol Tb3+ and 6% mol Yb3+ respectively, the intensity of NIR emission reaches its strongest.

[Preparation and luminescence of Eu3+ /Yb3+ codoped ZrO2 powders].

Samples of Eu3+ /Yb3+ co-doped ZrO2 powders were prepared by co-precipitation method. The dependence on the sintering temperature and doping concentration of the structure and luminescence was studied. The results confirmed that the sintering temperature has significant influence on the crystalline phases of ZrO2. As the sintering temperature increased the tetragonal phase was transformed into monoclinic phase. After sintered at 1150 degrees C, single monoclinic phase was observed. In contrast, with the increase in the doping concentration of Yb3+, the crystalline phase was also changed, and the monoclinic phase was transformed back to tetragonal phase. With 1% Eu3+ and 10% Yb3+ doping, single tetragonal phase presents. It was observed that the luminescent properties of Eu3+ ions in two structures were different. Experiment results reveal that the luminescence can be affected by both sintering temperature and doping concentration. With single Yb3+ doping, no NIR emission was observed under ultraviolet light excitation (270 nm). However, with Eu3+/Yb3+ codoping, NIR emission around 980 nm from Yb3+ ((2)F(5/2)-->(2)F(7/2)) was observed under the same excitation. Furthermore, it is confirmed that Yb3+ has the same excitation spectrum with Eu3+. This down-conversion result indicates that there is an energy transfer process between Eu3+ and Yb3+. Cooperative energy transfer process and cross-relaxation process were assigned as the possible mechanism for the near-infrared emission of Yb3+.