Lanthanide-Doped Core–Shell–Shell Nanocomposite for Dual Photodynamic Therapy and Luminescence Imaging by a Single X‑ray Excitation Source

Photodynamic therapy (PDT) could be highly selective and noninvasive, with low side effects as an adjuvant therapy for cancer treatment. Because excitation sources such as UV and visible lights for most of the photosensitizers do not penetrate deeply enough into biological tissues, PDT is useful only when the lesions are located within 10 mm below the skin. In addition, there is no prior example of theranostics capable of both PDT and imaging with a single deep-penetrating X-ray excitation source. Here we report a new theranostic scintillator nanoparticle (ScNP) composite in a core–shell–shell arrangement, that is, NaLuF₄:Gd­(35%),Eu­(15%)@NaLuF₄:Gd­(40%)@NaLuF₄:Gd­(35%),Tb­(15%), which is capable of being excited by a single X-ray radiation source to allow potentially deep tissue PDT and optical imaging with a low dark cytotoxicity and effective photocytotoxicity. With the X-ray excitation, the ScNPs can emit visible light at 543 nm (from Tb³⁺) to stimulate the loaded rose bengal (RB) photosensitizer and cause death of efficient MDA-MB-231 and MCF-7 cancer cells. The ScNPs can also emit light at 614 and 695 nm (from Eu³⁺) for luminescence imaging. The middle shell in the core−shell−shell ScNPs is unique to separate the Eu³⁺ in the core and the Tb³⁺ in the outer shell to prevent resonance quenching between them and to result in good PDT efficiency. Also, it was demonstrated that although the addition of a mesoporous SiO₂ layer resulted in the transfer of 82.7% fluorescence resonance energy between Tb³⁺ and RB, the subsequent conversion of the energy from RB to generate ¹O₂ was hampered, although the loaded amount of the RB was almost twice that without the mSiO₂ layer. A unique method to compare the wt % and mol % compositions calculated by using the morphological transmission electron microscope images and the inductively coupled plasma elemental analysis data of the core, core–shell, and core–shell–shell ScNPs is also introduced

Estimating binding free energy of a putative growth factors EGF–VEGF complex – a computational bioanalytical study

<p>Epidermal growth factor (EGF) and homodimeric vascular endothelial growth factor (VEGF) bind to cell surface receptors. They are responsible for cell growth and angiogenesis, respectively. Docking of the individual proteins as monomeric units using ZDOCK 2.3.2 reveals a partial blocking of the receptor binding site of VEGF by EGF. The receptor binding site of EGF is not affected by VEGF. The calculated binding energy is found to be intermediate between the binding energies calculated for Alzheimer’s Aß42 and the barnase/barstar complex.</p

Dissociation kinetics of macrocyclic trivalent lanthanide complexes of 1-oxa-4,7,10-triazacyclododecane-4,10-diacetic acid (H₂ODO2A)

<div><p>The dissociation kinetics of selected trivalent lanthanide (Ln³⁺, Ln=La, Pr, Eu, Er, Lu) complexes of the macrocyclic ligand H₂ODO2A (1-oxa-4,7,10-triazacyclododecane-4,10-diacetic acid), LnODO2A⁺, were studied in the [H⁺] range (0.1–2.4) × 10⁻⁴ M in the temperature range 15–45 °C. Excess Cu²⁺ ions were used as the scavenger for the ligand in acetate–acetic acid buffer medium. The dissociation reactions are independent of [Cu²⁺] and follow the rate law <i>k</i>_obs = <i>k</i>_d + <i>k</i>_AC[Acetate] + K′<i>k</i>_lim[H⁺]/(1 + K′[H⁺]), where <i>k</i>_d, <i>k</i>_AC, and <i>k</i>_lim are the respective dissociation rate constants for the [H⁺]-independent, acetate-assisted, and the [H⁺]-dependent limiting pathways; K′ is the equilibrium constant for the protonation reaction LnODO2A⁺ + H⁺ LnODO2AH²⁺. The dissociation rates of LnODO2A⁺ complexes are all faster than those of the corresponding LnDO2A⁺ complexes (DO2A²⁻ is the fully deprotonated dianion of the ligand H₂DO2A, 1,4,7,10-tetrazacyclo-dodecane-1,7-diacetic acid), consistent with the notion that LnODO2A⁺ complexes are kinetically more labile and thermodynamically less stable than the corresponding LnDO2A⁺ complexes, and H₂ODO2A is not pre-organized for Ln³⁺ ion complexation but H₂DO2A is.</p></div

Hydrolysis and DFT structural studies of dinuclear Zn(II) and Cu(II) macrocyclic complexes of <i>m</i>-12N₃O-dimer and the effect of pH on their promoted HPNP hydrolysis rates

<p>The synthesis of the ligand, <i>m</i>-12N₃O-dimer (1,3-bis(1-oxa-4,7,10-triazacyclododecan-7-yl)methyl)benzene, L), and the stability and hydrolysis constants of its dinuclear Zn(II) and Cu(II) complexes are reported, in addition to the effect of pH on HPNP (2-hydroxypropyl-4-nitrophenylphosphate) hydrolysis reaction rates promoted by these complexes. Various structural possibilities of the [Zn₂L] and [Cu₂L] hydrolytic species derived from solution equilibrium modeling are predicted from density functional theory (DFT) studies to correlate with the promoted HPNP hydrolysis reaction rates and to establish the structure–function–reactivity relationship. Upon deprotonation [Zn₂L(OH)]³⁺ tends to form a structure with a “closed-form” conformation where it is not possible for <i>para</i>-isomers. At pH >8, the formation of the closed-form [Zn₂L(OH)₂]²⁺ and [Zn₂L(<i>μ</i>-OH)(OH)₂]⁺ species led to faster promoted HPNP hydrolysis rates than the [Zn₂L(OH)]³⁺ species. On the other hand, the observed rates of the Cu₂L-promoted HPNP hydrolysis reaction were much slower than those of the [Zn₂L]-promoted ones due to formation of the inactive, di-<i>μ</i>-OH⁻ bridged closed-form [Cu₂L(<i>μ</i>-OH)₂]²⁺ structure at high pH. The effects of solvent molecules and the use of higher DFT computation levels, i.e., M06 and M06–2X, in conjunction with cc-pVDZ and cc-pVTZ basis sets on the DFT-predicted structures for both [Cu(12N₄)(H₂O)]²⁺ and [Zn(12N₃O)(H₂O)₂]²⁺ complexes were also evaluated and compared with those using the B3LYP/6–31G* method.</p