Bioactive Composite Nanoparticles for Effective Microenvironment Regulation, Neuroprotection, and Cell Differentiation

Brain injuries typically result in neural tissue damage and trigger a permanent neurologic deficit. Current methods exhibit limited effects due to the harsh microenvironment of injury regions rich in reactive oxygen species (ROS). Herein, a microenvironment regulation combined with cellular differentiation strategy is designed for repairing injured nerves. We prepare PMNT/F@D-NP nanoparticles comprising a bioactive polythiophene derivative (PMNT) and fullerenol as a multifunctional theranostic nanoplatform. PMNT/F@D-NPs can significantly reduce the accumulation of ROS in the simulated ischemic brain injury trial and inhibit cell apoptosis due to the effective free radical scavenging ability of fullerenol. Interestingly, the bioactive PMNT/F@D-NPs can promote the proliferation and differentiation of neurons, confirmed by immunofluorescence and western blotting studies. This newly developed strategy exhibits a combinatorial therapeutic effect by promoting nerve cell survival and differentiation while improving the microenvironment in the damaged area, which paves the way for the rational design of multifunctional agents for brain injury therapy

Phylogenetic relationships in <i>Aconitum</i> obtained from an ML analysis of the combined cpDNA dataset.

<p>Numbers above branches are posterior probabilities; numbers below branches are bootstrap values for maximum parsimony/maximum likelihood analyses. “-” indicates that support is less than 50% bootstrap value. Tamura’s (1995) classification of subgen. <i>Lycoctonum</i> are shown on the right. Accessions with a different placement in the nrDNA tree are indicated in bold. The clade of subgen. <i>Aconitum</i> has been collapsed for saving space (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0171038#pone.0171038.s001" target="_blank">S1 Fig</a> for the complete topology).</p

Phylogeny and reclassification of <i>Aconitum</i> subgenus <i>Lycoctonum</i> (Ranunculaceae)

<div><p>Phylogenetic analyses were performed using multiple nuclear (ITS and ETS) and chloroplast regions (<i>ndh</i>F-<i>trn</i>L, <i>psb</i>A-<i>trn</i>H, <i>psb</i>D-<i>trn</i>T, and <i>trn</i>T-<i>trn</i>L) to test the monophyly of <i>Aconitum</i> subgen. <i>Lycoctonum</i> (Ranunculaceae) and reconstruct the phylogenetic relationships within the subgenus. The subgenus as currently circumscribed is revealed to be polyphyletic. To achieve its monophyly, sect. <i>Galeata</i> and sect. <i>Fletcherum</i>, both being unispecific and each having a unique array of characters (the latter even having the aberrant base chromosome number of <i>x</i> = 6), must be removed from the subgenus. The subgenus <i>Lycoctonum</i> should thus be redefined to include only two sections, the unispecific sect. <i>Alatospermum</i> and the relatively species-rich sect. <i>Lycoctonum</i>. The section <i>Alatospermum</i>, which is both morphologically and karyologically in the primitive condition, is resolved as the first diverging lineage of the subgenus <i>Lycoctonum</i> clade. The monophyly of sect. <i>Lycoctonum</i> is strongly supported, but all the ten series currently recognized within the section are revealed to be para- or poly-phyletic. Five major clades are recovered within the section. We propose to treat them as five series: ser. <i>Crassiflora</i>, ser. <i>Scaposa</i>, ser. <i>Volubilia</i>, ser. <i>Longicassidata</i>, and ser. <i>Lycoctonia</i>. Thus, a formal reclassification of subgen. <i>Lycoctonum</i> is presented, which involves segregating both sect. <i>Galeata</i> and sect. <i>Fletcherum</i> from the subgenus as two independent subgenera within the genus <i>Aconitum</i>, reinstating one series (ser. <i>Crassiflora</i>) and abolishing six series (ser. <i>Laevia</i>, ser. <i>Longibracteolata</i>, ser. <i>Micrantha</i>, ser. <i>Ranunculoidea</i>, ser. <i>Reclinata</i>, and ser. <i>Umbrosa</i>) within sect. <i>Lycoctonum</i>. The series affiliation of some species within the section is adjusted accordingly.</p></div

<i>P</i>-values of the WSR and AU tests.

<p>The pruned datasets are reconstructed from the original datasets by excluding <i>Aconitum apetalum</i>, two accessions of <i>A</i>. <i>barbatum</i> var. <i>barbatum</i> (ZY69 and GQ150), <i>A</i>. <i>fletcheranum</i>, <i>A</i>. <i>gigas</i> var. <i>hondoense</i>, and <i>A</i>. <i>moschatum</i>. Bold-faced values indicate rejection of the null hypothesis with 95% confidence.</p

Statistics of the nuclear and chloroplast sequence datasets.

<p>Statistics of the nuclear and chloroplast sequence datasets.</p

Phylogenetic relationships in <i>Aconitum</i> obtained from an ML analysis of the combined cpDNA and nrDNA dataset.

<p>Numbers above branches are posterior probabilities; numbers below branches are bootstrap values for maximum parsimony/maximum likelihood analyses. “-” indicates that support is less than 50% bootstrap value. Tamura’s (1995) classification and our new classification of subgen. <i>Lycoctonum</i> are shown on the right. Accessions with different placements between the cpDNA tree and the nrDNA tree are indicated in bold. The clade of subgen. <i>Aconitum</i> has been collapsed for saving space (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0171038#pone.0171038.s003" target="_blank">S3 Fig</a> for the complete topology).</p

<i>P</i>-values of the partition-homogeneity tests.

<p>The pruned datasets are reconstructed from the original datasets by excluding <i>Acontium apetalum</i>, two accessions of <i>A</i>. <i>barbatum</i> var. <i>barbatum</i> (ZY69 and GQ150), <i>A</i>. <i>fletcheranum</i>, <i>A</i>. <i>gigas</i> var. <i>hondoense</i>, and <i>A</i>. <i>moschatum</i>. Bold-faced values indicate rejection of the null hypothesis with 95% confidence.</p

A list of the primers used in this study.

<p>A list of the primers used in this study.</p

Historical classifications of <i>Aconitum</i> subgen. <i>Lycoctonum</i>.

<p>Historical classifications of <i>Aconitum</i> subgen. <i>Lycoctonum</i>.</p

Chemiluminescent Conjugated Polymer Nanoparticles for Deep-Tissue Inflammation Imaging and Photodynamic Therapy of Cancer

Deep-tissue optical imaging and photodynamic therapy (PDT) remain a big challenge for the diagnosis and treatment of cancer. Chemiluminescence (CL) has emerged as a promising tool for biological imaging and in vivo therapy. The development of covalent-binding chemiluminescence agents with high stability and high chemiluminescence resonance energy transfer (CRET) efficiency is urgent. Herein, we design and synthesize an unprecedented chemiluminescent conjugated polymer PFV-Luminol, which consists of conjugated polyfluorene vinylene (PFV) main chains and isoluminol-modified side chains. Notably, isoluminol groups with chemiluminescent ability are covalently linked to main chains by amide bonds, which dramatically narrow their distance, greatly improving the CRET efficiency. In the presence of pathologically high levels of various reactive oxygen species (ROS), especially singlet oxygen (1O2), PFV-Luminol emits strong fluorescence and produces more ROS. Furthermore, we construct the PFV-L@PEG-NPs and PFV-L@PEG-FA-NPs nanoparticles by self-assembly of PFV-Luminol and amphiphilic copolymer DSPE-PEG/DSPE-PEG-FA. The chemiluminescent PFV-L@PEG-NPs nanoparticles exhibit excellent capabilities for in vivo imaging in different inflammatory animal models with great tissue penetration and resolution. In addition, PFV-L@PEG-FA-NPs nanoparticles show both sensitive in vivo chemiluminescence imaging and efficient chemiluminescence-mediated PDT for antitumors. This study paves the way for the design of chemiluminescent probes and their applications in the diagnosis and therapy of diseases