Dual ligand targeting to different types of over-expressed receptors on cell surfaces is a promising strategy in nanomedicine. Here, by using dissipative particle dynamics simulations, the effect of the surface distribution and physicochemical properties of dual ligands on the cellular uptake of nanoparticles is systematically studied. It is found that the spontaneous rearrangement of dual ligands (from random to patterned distribution) on the nanoparticle surface can enhance the cellular uptake of nanoparticles. While the short length of ligands may restrict the ligand rearrangement, nanoparticles coated with short dual ligands cannot be fully wrapped by cell membranes unless the dual ligands are initially separated on the nanoparticle surface. Besides, when there exists a length mismatch or non-specific interaction between the dual ligands, dual-ligand targeting cannot enhance the uptake efficiency, either. Further, we also provide the design guidelines for surface decoration, and find that the Janus nanoparticle can make the most of dual-ligand targeting. These results can help understand how to better use dual ligands to achieve efficient cellular uptake, which may provide significant insights into the optimal design of future nanomaterials in drug delivery.
Efficient delivery of nanoparticles into specific cell interiors is of great importance in biomedicine. Recently, the pH-responsive micelle has emerged as one potential nanocarrier to realize such purpose since there exist obvious pH differences between normal tissues and tumors. Herein, by using dissipative particle dynamics simulation, we investigate the interaction of the pH-sensitive triblock copolymer micelles composed of ligand (L), hydrophobic block (C) and polyelectrolyte block (P) with cell membrane. It is found that the structure rearrangement of the micelle can facilitate its penetration into the lower leaflet of the bilayer. However, when the ligand-receptor specific interaction is weak, the micelles may just fuse with the upper leaflet of the bilayer. Moreover, the ionization degree of polyelectrolyte block and the length of hydrophobic block also play a vital role in the penetration efficiency. Further, when the sequence of the L, P, C beads in the copolymers is changed, the translocation pathways of the micelles may change from direct penetration to Janus engulfment. The present study reveals the relationship between the molecular structure of the copolymer and the uptake of the pH-sensitive micelles, which may give some significant insights into the experimental design of responsive micellar nanocarriers for highly efficient cellular delivery.
The origin of the self-activated luminescence in the apatite-type M5(PO4)3X (MPOX; M = Sr or Ba; X = Cl or Br) samples and the spectral assignment for cerium-doped Sr5(PO4)3Cl (SPOC) phosphors are determined from first-principles methods combined with hybrid density functional theory (DFT) calculations, using the standard PBE0 hybrid functional, with wave function-based embedded-cluster ab initio calculations (at the CASSCF/CASPT2/RASSI–SO level). Electronic structure calculations are performed in order to accurately derive the band gaps of the hosts, the locations of impurity states in the energy bands that are caused by native defects and doped Ce3+ ions, and the charge-compensation mechanisms of aliovalent doping. The calculations of defect formation energies under O-poor conditions demonstrate that the native defects are easily generated in the undoped MPOX samples prepared under reducing atmospheres, from which thermodynamic and optical transition energy levels, as well as the corresponding energies, are derived in order to interpret the luminescence mechanisms of the undoped MPOX as previously reported. Our calculations reveal that the self-activated luminescence is mainly attributed to the optical transitions of the excitons bound to the oxygen vacancies (VO), along with their transformation of the charge states 0 ↔ 1+. Furthermore, the eight excitation bands observed in the synchrotron radiation excitation spectra of SPOC: Ce3+, Na+ phosphors are successfully assigned according to the ab initio calculated energies and relative oscillator strengths of the 4f1 → 5d1–5 transitions for the Ce3+ ions at both the Sr(1) and Sr(2) sites in the host. It is hoped that the feasible first-principles approaches in this work are applied in order to explore the origins of the luminescence in undoped and lanthanide-doped phosphors, complementing the experiments from the perspective of chemical compositions and the microstructures of materials.
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