Core/Shell Structured Fe3O4@TiO2-DNM Nanospheres as Multifunctional Anticancer Platform: Chemotherapy and Photodynamic Therapy Research.

The dose-dependent toxicity and low specificity against cancerous cells have restricted the clinical use of daunomycin (DNM). Titanium dioxide (TiO2) has been wildly used as an inorganic photodynamic therapy (PDT) agent and drug carrier. To facilitate the targeted drug delivery and combined therapy, in the present study, TiO2-coated Fe3O4 nanoparticles (Fe3O4@TiO2 NPs) were employed to load DNM and the drug-loaded Fe3O4@TiO2-DNM Nps exhibited smart pH-controlled releasing and satisfactory cytotoxicity as well as photocytotocity. The combination of prussian blue staining and fluorescence methods evidenced the effortless cell internalization of the fabricated Fe3O4@TiO2-DNM Nps for the cancer cells. The cell cycle status experiments indicated that the as-prepared nanospheres arrested the S and G2/M periods of the cancer cell proliferation in the dark, and further induced the apoptosis under the irradiation of ultraviolet light. The cell apoptotic results revealed that the apoptosis induced by the Fe3O4@TiO2-DNM Nps was in the early stage. The constructed Fe3O4@TiO2-DNM NPs have been endowed with multifunctions that allow them to selectively deliver combinatorial therapeutic payload and exhibit integrated therapeutic effectiveness to tumors.

Synthesis, G-quadruplexes DNA binding, and photocytotoxicity of novel cationic expanded porphyrins.

Intensive reports allowed the conclusion that molecules with extended aromatic surfaces always do good jobs in the DNA interactions. Inspired by the previous successful researches, herein, we designed a series of cationic porphyrins with expanded planar substituents, and evaluated their binding behaviors to G-quadruplex DNA using the combination of surface-enhanced raman, circular dichroism, absorption spectroscopy and fluorescence resonance energy transfer melting assays. Asymmetrical tetracationic porphyrin with one phenyl-4-N-methyl-4-pyridyl group and three N-methyl-4-pyridyl groups exhibit the best G4-DNA binding affinities among all the designed compounds, suggesting that the bulk of the substituents should be matched to the width of the grooves they putatively lie in. Theoretical calculations applying the density functional theory have been carried out and explain the binding properties of these porphyrins reasonably. Meanwhile, these porphyrins were proved to be potential photochemotherapeutic agents since they have photocytotoxic activities against both myeloma cell (Ag8.653) and gliomas cell (U251) lines.

Heterotopic mesenteric ossification caused by trauma: A case report.

BACKGROUND: Heterotopic mesenteric ossification (HMO) is a clinically rare condition characterized by the formation of bone tissue in the mesentery. The worldwide reporting of such cases is limited to just over 70 instances in the medical literature. The etiology of HMO remains unclear, but the disease is possibly induced by mechanical trauma, ischemia, or intra-left lower quadrant abdominal infection, leading to the differentiation of mesenchymal stem cells into osteoblasts. Here, we present a rare case of HMO that occurred in a 34-year-old male, who presented with left lower quadrant abdominal pain. CASE SUMMARY: We report the case of a 34-year-old male patient who presented with left lower abdominal pain following trauma to the left lower abdomen. He subsequently underwent surgical treatment, and the postoperative pathological diagnosis was HMO. CONCLUSION: We believe that although there is limited literature and research on HMO, when patients with a history of trauma or surgery to the left lower abdomen present with corresponding imaging findings, clinicians should be vigilant in distinguishing this condition and promptly selecting appropriate diagnostic and therapeutic interventions.

In vitro study of the cytotoxicities of two mixed-ligand oxovanadium complexes on human hepatoma cells.

The cytotoxicities of two oxovanadium complexes, VOI [VO(satsc)(phen)] (satsc = salicylaldehyde thiosemicarbazone, phen = 1,10-phenanthroline) and VOII [VO(3,5-dibrsatsc)(phen)](3,5-dibrsatsc = 3,5-dibromosalicylaldehyde thiosemicarbazone), were studied by performing MTT assays on human hepatoma cell lines BEL-7402, HUH-7 and HepG2. The results showed that both the VOI and VOII complexes possess significant anti-proliferative effects. In addition, the anti-proliferative mechanism of the complexes was analyzed by cell cycle analysis and an apoptosis assay and by detecting the mitochondrial membrane potential (delta psi m). The experimental results showed that the complexes can cause a G0/G1 phase cell cycle arrest and can significantly decrease delta psi m, causing depolarization of the mitochondrial membrane. Notably, the two complexes induced apoptosis in BEL-7402 cells and displayed typical morphological apoptotic characteristics. The cytotoxicities of the VOII complex are significantly stronger than that of the VOI complex, suggesting that the cytotoxic effects of oxovanadium complexes may be associated with the electronic effects of the complexes.

Calcium carbonate end-capped, folate-mediated Fe3O4@mSiO2 core-shell nanocarriers as targeted controlled-release drug delivery system.

Magnetic mesoporous silica nanospheres (MMSN) were prepared and the surface was modified with cancer cell-specific ligand folic acid. Calcium carbonate was then employed as acid-activated gatekeepers to cap the mesopores of the MMSN, namely, MMSN-FA-CaCO3. The formation of the MMSN-FA-CaCO3 was proved by several characterization techniques, viz. transmission electron microscopy, zeta potential measurement, Fourier transform infrared spectroscopy, BET surface area measurement, and UV-Vis spectroscopy. Daunomycin was successfully loaded in the MMSN-FA-CaCO3 and the system exhibited sensitive pH stimuli-responsive release characteristics under blood or tumor microenvironment. Cellular uptake by folate receptor (FR)-overexpressing HeLa cells of the MMSN-FA-CaCO3 was higher than that by non-folated-conjugated ones. Intracellular-uptake studies revealed preferential uptake of these nanoparticles into FR-positive [FR(+)] HeLa than FR-negative [FR(-)]A549 cell lines. DAPI stain experiment showed high apoptotic rate of MMSN-FA-DNM-CaCO3 to HeLa cells. The present data suggest that the CaCO3 coating and folic acid modification of MMSN are able to create a targeted, pH-sensitive template for drug delivery system with application in cancer therapy.

Novel porphyrin-daunomycin hybrids: synthesis and preferential binding to G-quadruplexes over i-motif.

Encouraged by the enormous importance attributed to the structure and function of human telomeric DNA, herein we focused our attention on the interaction of a serious of newly prepared porphyrin-daunomycin (Por-DNR) hybrids with the guanine-rich single-strand oligomer (G4) and the complementary cytosine-rich strand (i-motif). Various spectral methods such as absorption and fluorescence titration, surface-enhanced Raman and circular dichroism spectrum were integrated in the experiment and it was found that these Por-DNR hybrids could serve as prominent molecules to recognize G4 and i-motif. What is more, interesting results were obtained that the hybrids with longer flexible links are more favorable in binding with both G4 and i-motif than the hybrid with shorter linkage. These Por-DNR hybrids may help to develop new ideas in the research of human telomeric DNA with small molecules.

Synthesis, DNA-binding, and photocleavage properties of a serious of porphyrin-daunomycin hybrids.

It is widely accepted that the pharmacological activities of anthracyclines antitumor agents express when the quinone-containing chromophore intercalates into base pairs of the duplex DNA. We have successfully synthesized and investigated the DNA-interactions of hybrids composed with quinone chromophore and cationic porphyrin. Herein, a clinic anticancer drug, daunomycin, is introduced to the porphyrin hybrids through different lengths of amide alkyl linkages, and their interactions and cleavage to DNA were studied compared with the previous porphyrin-quinone hybrids. Spectral results and the determined binding affinity constants (Kb) show that the attachment of daunomycin to porphyrin could improve the DNA-binding and photocleaving abilities. The porphyrin-daunomycin hybrids may find useful employment in investigating the ligand-DNA interaction.

Shedding light on the interactions of guanine quadruplexes with tricationic metalloporphyrins.

G-quadruplex DNA presents a potential target for the design and development of novel anticancer drugs. The porphyrin TMPyP4 was early reported to be a suitable motif for G-quadruplex DNA interaction. We inserted various metal ions such as Zn(II), Cu(II), Co(III) in the center of the aromatic core of tricationic TMPyP4-like porphyrin and examined their interactions with an antiparallel G-quadruplex DNA by a combination of spectroscopy and Job plot methods. Porphyrin metallation allowed the conclusion that the presence of one axial ligand perpendicular to the aromatic plane did not hamper π-π stacking interactions between quadruplex and the aromatic parts of porphyrin on the other face while porphyrin with two axial ligands was unable to undergo such interaction due to geometrical factors. Free base porphyrin and porphyrin without axial ligands are able to stabilize the quadruplex structure to a greater extent than the other metal complexes and thus may be potential anti-cancer drugs.