Mingxin Wang

A strategy for photothermal conversion of polymeric nanoparticles by polyaniline for smart control of targeted drug delivery

The near-infrared (NIR)-mediated novel strategy to control the drug release from nanocarriers has developed rapidly in recent decades. Polyaniline as a non-cytotoxic and electroactive material for studying cellular proliferation has attracted great attention in recent years. In the present work, polyaniline-mediated polymeric nanoparticles were developed to target the delivery of cisplatin and release it in a controllable way. The prepared polyaniline nanoparticles displayed a size of 90xa0±xa01.0 nm, a favorable morphology in water, and could be targeted to tumors through the high affinity between trastuzumab and the overexpressed Her2 in tumor cells. In addition, the developed nanoparticles demonstrated exciting photothermal conversion efficiency induced by NIR light and achieved significant cell inhibition efficiency (93.97%) in vitro when exposed to an 808 nm NIR laser with the power of 1.54 W for 5 min. Therefore, the developed external control release delivery system with excellent specificity and high cytotoxicity exhibited great potential in cell research and our research demonstrated that the polyaniline also has potential in the application of photothermal conversion in biomedicine.

Near infrared radiated stimulus-responsive liposomes based on photothermal conversion as drug carriers for co-delivery of CJM126 and cisplatin

Synergistic therapy has caused increasing interest in recent treatment of cancer owing to its preferable therapeutic efficiency to most single antineoplastic protocol. Herein, we design a co-delivery two drugs nanosystem based on biodegradable liposomes, loading cisplatin, Indocyanine green (ICG), and CJM126 coupled with cholesterol derivative (CJM-Chol) for the purpose of synergistic therapy. The obtained nanoparticles showed a uniform diameter of 103.8nm and a favorable morphology. The investigation on near infrared radiated (NIR) responsive release showed that NIR mediated photothermal conversion induced a controllable drug release from liposomes. Furthermore, the designed liposomes (only 50μg/mL) displayed an inspiring photothermal conversion efficiency and received a high temperature (65.6°C, Tm=42°C) when exposed to an 808nm near infrared laser (1.54W, 5min). Besides, it turned out that the delivery system could be efficiently endocytosed by tumor cells, which attributed to its admirable biocompatibility and the targeting role of folate. The prepared nanoparticles showed significantly excellent inhibitory effect (3.05% cell viability in 24h) on MDA-MB-231 cells when added irradiation as compared with free cisplatin (28.41%) or treatment without NIR (11.24%) in our study. Our research highlights the present nanoparticles provide a promising strategy for targeted delivery and photothermal treatment.

Co-delivery of cisplatin and CJM-126 via photothermal conversion nanoparticles for enhanced synergistic antitumor efficacy

Polymeric biomaterials that can be smartly disassembled through the cleavage of the covalent bonds in a controllable way upon an environmental stimulus such as pH change, redox, special enzymes, temperature, or ultrasound, as well as light irradiation, but are otherwise stable under normal physiological conditions have attracted great attention in recent decades. The 2-(4-aminophenyl) benzothiazole molecule (CJM-126), as one of the benzothiazole derivatives, has exhibited a synergistic effect with cisplatin (CDDP) and restrains the bioactivities of a series of human breast cancer cell lines. In our study, novel NIR-responsive targeted binary-drug-loaded nanoparticles encapsulating indocyanine green (ICG) dye were prepared as a new co-delivery and combined therapeutic vehicle. The prepared drug-loaded polymeric nanoparticles (TNPs/CDDP-ICG) are stable under normal physiological conditions, while burst drugs release upon NIR laser irradiation in a mild acidic environment. The results further confirmed that the designed co-delivery platform showed higher cytotoxicity than the single free CDDP due to the synergistic treatment of CJM-126 and CDDP in vitro. Taken together, the work might provide a promising approach for effective site-specific antitumor therapy.

Complexation of different transition metals with 4,4'-dimethyl-2,2'-bipyridine: Crystal structure, UV spectra and Hirshfeld surfaces.

Four new complexes, [Co(dmbpy)2(dca)2]·CH3OH (1), [Ni(dmbpy)2(dca)2]·CH3OH (2), [Zn(dmbpy)2(dca)2]·(3) and [Cu(dmbpy)2(OH)2]·5H2O (4) (dca=dicyanamide), derived from 4,4-dimethyl-2,2-bipyridine (dmbpy) have been synthesized and characterized by elemental analysis, TGA and single-crystal X-ray diffraction. Crystal structures and Hirshfeld surfaces analysis revealed that the complexes 1-3 were mainly supported by OH⋯N, CH⋯N and π⋯π intermolecular interactions, and for complex 4, the uncoordinated water molecules play a key role in the construction of the 3D stacking motif. UV spectrum measurements demonstrate that all of the complexes show typical metal to ligand charge transfer (MLCT) absorption bands between 301 and 306nm. Moreover, after complexation, the absorption maximum bands about intraligand π→π* transitions similarly show slightly red shift compared to dmbpy ligand, consisting with the DFT calculations.

A dual-targeting strategy for enhanced drug delivery and synergistic therapy based on thermosensitive nanoparticles

Abstract The functionalized nanoparticles have been widely studied and reported as carriers of drug transport recently. Furthermore, many groups have focused more on developing novel and efficient treatment methods, such as photodynamic therapy and photothermal therapy, since both therapies have shown inspiring potential in the application of antitumor. The mentioned treatments exhibited the superiority of cooperative manner and showed the ability to compensate for the adverse effects caused by conventional monotherapy in proposed strategies. In view of the above descriptions, we formulated a thermosensitive drug delivery system, which achieved the enhanced delivery of cisplatin and two photosensitizers (ICG and Ce6) by dual-targeting traction. Drawing on the thin film hydration method, cisplatin and photosensitizers were encapsulated inside nanoparticles. Meanwhile, the targeting peptide cRGD and targeting molecule folate can be modified on the surface of nanoparticles to realize the active identification of tumor cells. The measurements of dynamic light scattering showed that the prepared nanoparticles had an ideal dispersibility and uniform particle size of 102.6 nm. On the basis of the results observed from confocal laser scanning microscope, the modified nanoparticles were more efficient endocytosed by MCF-7 cells as a contrast to SGC-7901 cells. Photothermal conversion-triggered drug release and photo-therapies produced a significant apoptosis rate of 85.9% on MCF-7 cells. The distinguished results made it believed that the formulated delivery system had conducted great efforts and innovations for the realization of concise collaboration and provided a promising strategy for the treatment of breast cancer.

FA and cRGD dual modified lipid-polymer nanoparticles encapsulating polyaniline and cisplatin for highly effective chemo-photothermal combination therapy

Abstract A combination of chemotherapy and photothermal therapy as a promising strategy has exhibited noticeable therapeutic effect on cancer therapy. To ensure the exertion of synergistic effect on a tumor region, a multifunctional vehicle for selectively delivering therapeutic agent into tumor cells is highly desirable. Thus, folate-poly (ethylene glycol)-distearoylphosphatidylcholine (FA-PEG-DSPE), cRGD [cyclic (Arg-Gly-Asp-D-Phe-Lys)]-PEG-DSPE and lecithin were employed to develop dual modified nanoparticles (FA/cRGD-PNPs) encapsulating polyaniline and cisplatin by a film-ultrasonic dispersion method. The FA/cRGD-PNPs showed a uniform size of 102.7 nm, remarkable stability and monodispersity, and highly localized temperature respond. Compared to chemo or photothermal treatment alone, the combined treatment on cells in vitro significantly suppressed the survival rate of MDA-MB-231 cells (1.87%) and MGC-803 cells (2.37%) treated for 48 h. The results further indicated the induced cell apoptosis rate of MDA-MB-231 cells reached to 92.6% with treatment for 24 h. Hence, our research highlights the great potential in drug delivery and the combination of chemotherapy and photothermal therapy.

Cisplatin and Ce6 loaded polyaniline nanoparticles: An efficient near-infrared light mediated synergistic therapeutic agent

Lipid-polymer hybrid nanoparticle was suggested to be a new and promising drug delivery agent due to the suitable particle size and controllable release. However, the low drug loading capacity has been a critical problem in the improvement of the nano-carrier systems. At present work, we have designed and developed smart nanoparticles with cholesterol-cisplatin (IV) conjugate contained to enhance the drug loading capacity. The predesigned drug delivery system showed enhanced synergistic effect through co-delivery of cisplatin and Ce6 and the drug released in a controllable way due to the polyaniline mediated photothermal conversion. The prepared polyaniline nanoparticles showed a favorable particle size of 109.6u202fnm and spread harmoniously in aqueous solution. Moreover, the near infrared radiation (NIR) stimulus-responsive characteristic of the polyaniline nanoparticles prompts the release of cisplatin from the nanoparticles inside the cytoplasm and the αvβ3/αvβ5 integrins targeted ligands (cRGD) enhanced the cellular uptake of the polyaniline nanoparticles in receptor-overexpressing MCF-7 cells. Furthermore, the singlet oxygen generated by Ce6 further enhances the cytotoxicity and obtained the expected synergistic effect with cisplatin. Thus, the prepared cRGD-conjugated co-delivery of cisplatin and Ce6 polyaniline nanoparticles consider to be a promising nanoplatform in nano-biomedicine.

1,3-dimethyl-6-nitroacridine derivatives induce apoptosis in human breast cancer cells by targeting DNA

Abstract The acridine derivatives can interact with the double-stranded DNA, which is regarded as the biological target of the anticancer drugs in cancer treatment. We designed and synthesized a new series of 1,3-dimethyl-6-nitroacridine derivatives as potential DNA-targeted anticancer agents. These compounds could partially intercalate into the calf thymus DNA, differing from the parent acridine. The results showed that the substitutions of the acridine ring had great effect on DNA binding affinity. The binding constants determined by UV-vis spectroscopy were found to be 105u2009M−1 grade. Anticancer activity of these compounds was screened using MTT assay. Most compounds inhibited 50% cancer cell growth at concentration below 30u2009μM, the results were consistent with the DNA binding ability. Compounds 1 and 6 were found to have more effective cytotoxicity, especially in human breast cancer cell lines. To investigate the action mechanism, we studied cell apoptosis, morphological changes, and cell cycle distribution in MCF-7 and MDA-MB-231 cells. Compounds 1 and 6 caused MCF-7 and MDA-MB-231 cells death due to apoptosis, and induced cell apoptosis in a dose-dependent manner. They also had significant effect on cell cycle progression and arrested cell cycle at G2/M phase. The results demonstrated that compounds 1 and 6 are promising candidates for cancer treatment.