RESUMO
Research on nanomedicines has rapidly progressed in the past few years. However, due to the limited size of nuclear pores (9-12 nm), the nuclear membrane remains a difficult barrier to many nucleus-targeting agents. Here, we report the development of a general platform to effectively deliver chemical compounds such as drug molecules or nanomaterials into cell nuclei. This platform consists of a polyamine-containing polyhedral oligomeric silsesquioxane (POSS) unit, a hydrophilic polyethylene glycol (PEG) chain, and the photosensitizer rose bengal (RB), which can self-assemble into nanoparticles (denoted as PPR NPs). Confocal fluorescence imaging showed that PPR NPs mainly located in lysosomes after cellular internalization. After mild light irradiation, however, PPR NPs effectively disrupted lysosomal structures by singlet oxygen (1O2) oxidation and substantially accumulated on nuclear membranes, which enabled further disruption of the membrane integrity and promoted their final nuclear entry. Next, we selected two chemotherapeutic agents (10-hydroxycamptothecine and docetaxel) and a fluorescent dye (DiD) as payloads of PPR NPs and successfully demonstrated that this nanocarrier could efficiently deliver them into cell nuclei in a light-controlled manner. In addition to molecular compounds, we have also demonstrated that PPR NPs could facilitate the nuclear entry of nanomaterials, including Prussian blue NPs as well as gold nanorods. Compared to traditional strategies for nuclear delivery, this highly controllable nanoplatform avoids complicated modification of nucleus-targeting ligands and is generally applicable to both molecular compounds and nanomaterials.
Assuntos
Núcleo Celular/química , Sistemas de Liberação de Medicamentos , Luz , Nanopartículas/química , Camptotecina/análogos & derivados , Camptotecina/química , Camptotecina/farmacologia , Linhagem Celular Tumoral , Núcleo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Docetaxel , Corantes Fluorescentes/química , Humanos , Compostos de Organossilício/química , Tamanho da Partícula , Poliaminas/química , Polietilenoglicóis/química , Rosa Bengala/química , Taxoides/química , Taxoides/farmacologiaRESUMO
Novel photocurable ternary polymer networks were prepared by incorporating N-(4-hydroxy-3-methoxybenzyl)-acrylamide (HMBA) into a cross-linked thiol-ene network based on poly(ethylene glycol)diacrylate (PEGDA) and (mercaptopropyl)methylsiloxane homopolymers (MSHP). The ternary network materials displayed bactericidal activity against Escherichia coli and Staphylococcus aureus and reduced the attachment of marine organism Phaeodactylum tricornutum. Extensive soaking of the polymer networks in aqueous solution indicated that no active antibacterial component leached out of the materials, and thus the ternary thiol-ene coating killed the bacteria by surface contact. The surface structures of the polymer networks with varied content ratios were studied by sum frequency generation (SFG) vibrational spectroscopy. The results demonstrated that the PDMS Si-CH3 groups and mimic-capsaicine groups are predominantly present at the polymer-air interface of the coatings. Surface reorganization was apparent after polymers were placed in contact with D2O: the hydrophobic PDMS Si-CH3 groups left the surface and returned to the bulk of the polymer networks, and the hydrophilic PEG chains cover the polymer surfaces in D2O. The capasaicine methoxy groups are able to segregate to the surface in an aqueous environment, depending upon the ratio of HMBA/PEGDA. SFG measurements in situ showed that the antibacterial HMBA chains, rather than the nonfouling PEG, played a dominant role in mediating the antibiofouling performance in this particular polymer system.
RESUMO
Adhesion is important in many industrial applications including those in the microelectronics industry. Flip-chip assemblies commonly utilize epoxy underfills to promote reliability and the buried interfacial structure of underfills is crucial to device lifetime. Poor adhesion at this interface can cause premature device failure. One method to increase adhesion strength is to plasma treat the substrate attached to underfills, however, the mechanism of this increase in adhesion strength has not been thoroughly investigated at the molecular level in situ, because it is difficult to probe a buried interface where the adhesion occurs. In this work, sum frequency generation (SFG) vibrational spectroscopy was utilized to investigate the buried polymer/epoxy resin interface at the molecular level. Plasma treatment was performed on the polymer surfaces and the effects were examined. The buried interfaces between the polymer surface before and after plasma treatment and epoxy were then investigated to understand if the effects of the treatment can be observed using SFG. It was found that the molecular structure of the buried interface of the pristine polymer surface in contact with epoxy is drastically different from the buried interface of the plasma treated surface with epoxy. The buried interface containing the plasma treated polymer surface was found to be considerably more disordered and had much higher adhesion strength. This research elucidates the plasma treatment effects on structures and properties of buried polymer/epoxy interfaces, providing in-depth understanding on the mechanism of adhesion strength increase facilitated by plasma treatment.
RESUMO
The structure of a prototype CH···π system, benzene···acetylene, has been determined in the gas phase using Fourier-transform microwave spectroscopy. The spectrum is consistent with an effective C(6v) structure with an H···π distance of 2.4921(1) Å. The HCCH subunit likely tilts by ~5° from the benzene symmetry axis. The dipole moment was determined to be 0.438(11) D from Stark effect measurements. The observed intermolecular distance is longer than in similar benzene···HX complexes and than the distances observed in the benzene···HCCH cocrystal and predicted by many high level ab initio calculations; however, the experimentally estimated binding energy of 7.1(7) kJ mol(-1) is similar to previously studied benzene···HX complexes. Several additional sets of transitions were observed in the rotational spectrum, likely corresponding to excited states arising from low energy intermolecular vibrational modes of the dimer.
RESUMO
The rotational spectra for the normal isotopic species and for six (13)C singly substituted isotopologues (in natural abundance) of the fluorobenzene···acetylene (C6H5F···HCCH) weakly bound dimer have been measured in the 6.5-18.5 GHz region using chirped-pulse Fourier-transform microwave spectroscopy. The HCCH molecule interacts with the fluorobenzene via a CH···π contact and is determined to lie almost over the center of, and approximately perpendicular to, the aromatic ring, with an H···π distance (perpendicular distance from the H atom to the ring plane) of around 2.492(47) Å; a slight tilt of HCCH towards the para carbon atom of the fluorobenzene is evident. Binding energies of this complex and related benzene and fluorobenzene dimers obtained from the pseudodiatomic approximation are compared and indicate that fluorobenzene···acetylene lies among the more weakly bound of the complexes exhibiting some type of CH···π interaction.
RESUMO
Mitophagy is a specific self-protective autophagic process that degrades damaged or dysfunctional mitochondria, and is generally considered to reduce the effectiveness of mitochondria-targeted therapies. Here, we report an energy depletion-based anticancer strategy by selectively activating excessive mitophagy in cancer cells. We fabricate a type of mitochondria-targeting nanomicelles via the self-assembly of D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and dc-IR825 (a near-infrared cyanine dye and a photothermal agent). The TPGS/dc-IR825 nanomicelles enable mitochondrial damage in cancer cells, which, for self-protection, activate two autophagic pathways, (1) mitophagy and (2) adenosine triphosphate (ATP) shortage-triggered autophagy. However, the excessive mitophagy/autophagy activities far surpass the degradative capacity of autolysosomes, leading to the formation of micrometer-sized vacuoles and degradation blockage. Immunofluorescence staining and Western blot analysis reveal that the nanomicelle-treated cancer cells are under severe ATP shortage, which eventually causes substantial cell death. Moreover, the nanomicelles intravenously injected into tumor-bearing mice show high tumor accumulation, long tumor retention, and inhibit the tumor growth by inducing excessive mitophagy/autophagy and energy depletion in tumor cells. Additional near-infrared laser irradiation treatment further enhances the in vitro and in vivo anticancer efficiencies of the nanomicelles, due to the excellent photothermal and photodynamic effects of dc-IR825. We believe that this work highlights the important role of mitophagy/autophagy in treating cancers.