Cu_2–<i>x</i>S Nanocrystals Cross-Linked with Chlorin e6-Functionalized Polyethylenimine for Synergistic Photodynamic and Photothermal Therapy of Cancer

Achieving an integrated system for combinational therapy of cancer with enhanced efficacy is always a challenge. A multifunctional system (CCeT nanoparticles (NPs)) for a synergistic photodynamic and photothermal cancer therapy was successfully developed. This system is composed of Cu_2–<i>x</i>S nanoclusters functionalized with chlorin e6 (Ce6)-conjugated branched polyethylenimine (PEI-Ce6) and mitochondria-targeting 3-(carboxypropyl)­triphenylphosphonium bromide (TPP-COOH). The colocalization of the resulted CCeT NPs inside the mitochondria of cancer cells was proven. The CCeT NPs exhibited significant photodynamic therapy (PDT) efficacy due to efficient singlet oxygen (¹O₂) generation triggered by a 630 nm laser. This system also showed excellent photothermal conversion capability upon the irradiation of 808 nm laser for photothermal therapy (PTT). In particular, the platform achieved nearly 100% inhibitory rate of the tumor growth in vivo through combinational PDT and PTT. Thus, the CCeT NPs could efficiently inhibit the tumor growth in vitro and in vivo by combinational PDT and PTT, offering synergistic therapeutic efficiency as compared to PTT or PDT alone

Axial Ligand Effects on Vibrational Dynamics of Iron in Heme Carbonyl Studied by Nuclear Resonance Vibrational Spectroscopy

Nuclear resonance vibrational spectroscopy (NRVS) and density functional theory calculation (DFT) have been applied to illuminate the effect of axial ligation on the vibrational dynamics of iron in heme carbonyl. The analyses of the NRVS data of five- (5c) and six-coordinate (6c) heme–CO complexes indicate that the prominent feature of ⁵⁷Fe partial vibrational density of state (⁵⁷FePVDOS) at the 250–300 cm^–1 region is significantly affected by the association of the axial ligand. The DFT calculations predict that the prominent ⁵⁷FePVDOS is composed of iron in-plane motions which are coupled with porphyrin pyrrole in-plane (ν₄₉, ν₅₀, and ν₅₃), an out-of-plane (γ₈) (two of four pyrrole rings include the in-plane modes, while the rest of pyrrole rings vibrate along the out-of-plane coordinate), and out-of-phase carbonyl C and O atom displacement perpendicular to the Fe–C–O axis. Thus, in the case of the 5c CO–heme the prominent ⁵⁷FePVDOS shows sharp and intense feature because of the degeneracy of the <i>e</i> symmetry mode within the framework of <i>C</i>_4<i>v</i> symmetry molecule, whereas the association of the axial imidazole ligand in the 6c complex with the lowered symmetry results in split of the degenerate vibrational energy as indicated by broader and lower intensity features of the corresponding NRVS peak compared to the 5c structure. The vibrational energy of the iron in-plane motion in the 6c complex is higher than that in 5c, implying that the iron in the 6c complex includes stronger in-plane interaction with the porphyrin compared to 5c. The iron in-plane mode above 500 cm^–1, which is predominantly coupled with the out-of-phase carbonyl C and O atom motion perpendicular to Fe–C–O, called as Fe–C–O bending mode (δ_Fe–C–O), also suggests that the 6c structure involves a larger force constant for the <i>e</i> symmetry mode than 5c. The DFT calculations along with the NRVS data suggest that the stiffened iron in-plane motion in the 6c complex can be ascribed to diminished pseudo-Jahn–Teller instability along the <i>e</i> symmetry displacement due to an increased <i>a</i>₁–<i>e</i> orbital energy gap caused by σ* interaction between the iron d_<i>z</i>² orbital and the nitrogen p orbital from the axial imidazole ligand. Thus, the present study implicates a fundamental molecular mechanism of axial ligation of heme in association with a diatomic gas molecule, which is a key primary step toward versatile biological functions

The Gleason index for animals in Jinggangshan Mountain (JGM).

<p>LXM, Luoxiao Mountain; WYM, Wuyi Mountain; NLM, Nanling Mountain; WLM, Wuling Mountain.</p

The distribution of overlapping animal species.

<p>√ stands for the species distributed in this mountain, and blank means the species didn’t find in this mountain.</p><p>There are more overlapping plant species distributed in JGM and WYM/WLM (166/192) than in JGM and LXM/NLM (71/67). The former two mountains are distributed to the east and west of JGM, and the latter two mountains are distributed to the north and south of JGM (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0120208#pone.0120208.t006" target="_blank">Table 6</a>). More overlapping plants species were distributed in JGM and the two mountains in the east (WYM) and west (WLM), while more overlapping animals species were distributed in JGM and the other two mountains in the north (LXM) and south (NLM).</p><p>The distribution of overlapping animal species.</p

The percentage of altitudinal distribution of Jinggangshan Mountain (JGM) and surrounding mountains.

<p>LXM, Luoxiao Mountain; WYM, Wuyi Mountain; NLM, Nanling Mountain; WLM, Wuling Mountain.</p

Comparison of the Gleason index of seed plant species, genera and families of Jinggangshan Mountain (JGM) and surrounding mountains.

<p>LXM, Luoxiao Mountain; WYM, Wuyi Mountain; NLM, Nanling Mountain; WLM, Wuling Mountain.</p

Geographic position of Jinggangshan Mountain formed by convergence of four mountains to one point.

<p>Geographic position of Jinggangshan Mountain formed by convergence of four mountains to one point.</p

The distribution of overlapping plant species.

<p>The distribution of overlapping plant species.</p

The percentage of slope distribution of Jinggangshan Mountain (JGM) and surrounding mountains.

<p>LXM, Luoxiao Mountain; WYM, Wuyi Mountain; NLM, Nanling Mountain; WLM, Wuling Mountain.</p

Comparison of the vertebrate biodiversity of JGM and surrounding mountains.

<p>JGM, Jinggangshan Mountain; LXM, Luoxiao Mountain, WYM, Wuyi Mountain; NLM, Nanling Mountain; WLM, Wuling Mountain. The data for LXM, WYM, NLM and WLM came from surveys in Guanshan Natural Reserve [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0120208#pone.0120208.ref045" target="_blank">45</a>], Wuyishan Area, Fujian Province [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0120208#pone.0120208.ref046" target="_blank">46</a>], Nanling National Natural Reserve [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0120208#pone.0120208.ref055" target="_blank">55</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0120208#pone.0120208.ref056" target="_blank">56</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0120208#pone.0120208.ref057" target="_blank">57</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0120208#pone.0120208.ref058" target="_blank">58</a>] and Badagongshan Mountain [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0120208#pone.0120208.ref059" target="_blank">59</a>], respectively.</p><p>Comparison of the vertebrate biodiversity of JGM and surrounding mountains.</p