RESUMO
Tumor acidic environment-activated combination therapy holds great promise to significantly decrease side effects, circumvent multiple drug resistance, and improve therapeutic outcomes for cancer treatment. Herein, Sorafenib/ZnPc(PS)4@FeIII-TA nanoparticles (SPFT) are designed with acid-environment turned-on fluorescence to report the activation of triple therapy including photodynamic, chemodynamic, and chemotherapy on hepatocellular carcinoma. The SPFT are composed of SP cores formulated via self-assembly of sorafenib and ZnPc(PS)4, with high drug loading efficiency, and FeIII-TA shells containing FeCl3 and tannic acid. Importantly, the nanoparticles suppress reactive oxygen species (ROS) generation of ZnPc(PS)4 due to their formation in nanoparticles, while assisting simultaneous uptake of the uploaded drugs in cancer cells. The tumor acidic environment initiates FeIII-TA decomposition and accelerates a chemodynamic reaction between FeII and H2O2 to generate toxic â¢OH. Then, the SP core is decomposed to separate ZnPc(PS)4 and sorafenib, which leads to fluorescence turning-on of ZnPc(PS)4, expedited photodynamic reactions, and burst release of sorafenib. Notably, SPFT shows low dark cytotoxicity to normal cells but exerts high potency on hepatocellular carcinoma cells under near-infrared light irradiation, which is much more potent than either sorafenib or ZnPc(PS)4 alone. This research offers a facile nanomedicine design strategy for cancer therapy.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanopartículas , Fotoquimioterapia , Carcinoma Hepatocelular/tratamento farmacológico , Linhagem Celular Tumoral , Compostos Férricos , Fluorescência , Humanos , Peróxido de Hidrogênio , Neoplasias Hepáticas/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Sorafenibe/farmacologiaRESUMO
The major challenges in photodynamic therapy (PDT) are the neutralization of cytotoxic reactive oxygen species (ROS) by the excessive antioxidant glutathione (GSH) in tumor cells, high self-aggregation of most photosensitizers (PSs), and long time to protect from light after treatment. Thus, to develop the molecular PSs for the improved and safe PDT in clinic, a novel and versatile PS (Mal-Pc) has been designed by di-substituting maleimides to the axial positions of silicon (â £) phthalocyanine. Owning to the conjugation of maleimides, Mal-Pc can not only entry tumor cells more easily and faster, but also can react with the intracellular overexpressed GSH after entry. In addition, upon electrophilic reaction with GSH, the inhibition of self-aggregation of Mal-Pc has been demonstrated by the restoration of the fluorescence emission in aqueous media. As a result, the intracellular ROS levels and photocytotoxicity of Mal-Pc are dramatically enhanced. Finally, the high hydrophilicity of the product GS-conjugates facilitates Mal-Pc eliminate from the normal cells more rapidly. Overall, this work revealed the high potential of the versatile molecular Mal-Pc for highly efficient and safe PDT in clinical translation.
Assuntos
Antineoplásicos , Glutationa , Maleimidas , Fármacos Fotossensibilizantes , Espécies Reativas de Oxigênio , Glutationa/antagonistas & inibidores , Maleimidas/química , Maleimidas/farmacologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Espécies Reativas de Oxigênio/antagonistas & inibidores , Antineoplásicos/química , Antineoplásicos/farmacologia , Humanos , Células Hep G2RESUMO
Although photodynamic therapy (PDT) has attracted great interest, the photosensitizers in clinical had weak inhibition on metastasis and invasion of cancers. Additionally the immune response induced by PDT was insufficient to eradicate cancer. Herein, indoximod, an inhibitor of indoleamine 2,3-dioxygenase (IDO), is introduced to concatenate with zinc phthalocyanines (ZnPc) for effectively overcoming above inadequacy. Due to indoximod moiety, photosensitizer 1-MT-Pc can obtain enhanced intracellular uptake and high reactive oxygen species (ROS) generation. More impressively, 1-MT-Pc can achieve remarkable photocytotoxicity towards TNBC cells and negligible damage to normal cells. Meanwhile, 1-MT-Pc effectively inhibits metastasis and invasion of TNBC cells. Importantly, 1-MT-Pc exhibit elevated inhibitory effect on 4T1 tumor by enhanced PDT and immunotherapy.
Assuntos
Fotoquimioterapia , Neoplasias de Mama Triplo Negativas , Linhagem Celular Tumoral , Humanos , Imunidade , Isoindóis/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio , Neoplasias de Mama Triplo Negativas/tratamento farmacológicoRESUMO
As growth factor receptor-2 (HER-2), progesterone receptor (PR) and estrogen receptor (ER) are scarce in triple-negative breast cancer (TNBC), it is a great challenge to combat TNBC with high tumor specificity and therapeutic efficacy. Most traditional treatments including surgical resection, chemotherapy, and radiotherapy would more or less cause serious side effects and drug resistance. Photodynamic therapy (PDT) has huge potential in the treatment of TNBC for minimal invasiveness, low toxicity, less drug resistance and high spatiotemporal selectivity. Inspired by the advantages of small-molecule-targeted PDT and the sensitization effect of myeloid cell leukemia-1 (MCL-1) inhibitor, a novel photosensitizer BC-Pc was designed by conjugating MCL-1 inhibitor with zinc phthalocyanines. Owning to 3-chloro-6-methyl-1-benzothiophene-2-carboxylic acid (BC) moiety, BC-Pc exhibits the high affinity towards MCL-1 and reduce its self-aggregation in TNBC cells. Therefore, MCL-1 targeted BC-Pc showed remarkable intracellular fluorescence and ROS generation in TNBC cells. Additionally, BC-Pc can selectively sensitize TNBC cells to ROS-induced damage, resulting in improved therapeutic effect to TNBC cells and negligible toxicity to normal cells. More importantly, BC-Pc can effectively inhibit the migration and invasion of TNBC cells, and enhance immune response, all of which will be beneficial to eradicate TNBC. To the best of our knowledge, BC-Pc is the novel MCL-targeted photosensitizer, which owns the amplified ROS-induced lethality and anticancer immune response for TNBC. Overall, our study provides a promising strategy to achieve targeting and highly efficient therapy of TNBC.
Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Proteína de Sequência 1 de Leucemia de Células Mieloides/uso terapêutico , Espécies Reativas de Oxigênio , Linhagem Celular Tumoral , ImunidadeRESUMO
The present study provides in vitro and in vivo evaluation of Paeoniae alba Radix (PR) on peripheral nerve regeneration. In the in vitro study, we found the PR caused a marked enhancement of the nerve growth factor-mediated neurite outgrowth from PC12 cells as well as their expression of growth associated protein 43 and synapsin I. In the in vivo study, silicone rubber chambers filled with the PR water extract were used to bridge a 10-mm sciatic nerve defect in rats. At the conclusion of 8 weeks, regenerated nerves in the PR groups, especially at 1.25 mg ml(-1) had a higher rate of successful regeneration across the wide gap, relatively larger mean values of total nerve area, myelinated axon count and blood vessel number, and a significantly larger nerve conductive velocity compared to the control group (P < .05). These results suggest that the PR extract can be a potential nerve growth-promoting factor, being salutary in aiding the growth of injured peripheral nerve.
RESUMO
The asymmetric unit of the title coordination polymer, [Gd(2)(C(7)H(4)O(5)S)(2)(C(2)O(4))(H(2)O)(6)](n) or [Gd(2-SB)(ox)(0.5)(H(2)O)(3)](2n) (2-SB is 2-sulfonatobenzoate and ox is oxalate), (I), consists of one Gd(III) ion, one 2-SB anion, three coordinated water molecules and one half of an ox ligand. The ox ligand is located on a crystallographic inversion centre. The Gd(III) centre shows a distorted tricapped trigonal-prismatic coordination formed by nine O atoms from two 2-SB anions, one ox ligand and three coordinated water molecules. The carboxylate and sulfonate groups of the 2-SB anions adopt µ(2)-η(1):η(2) and µ(1)-η(0):η(0):η(1) coordination modes to link two Gd(III) ions, generating a centrosymmetric binuclear [Gd(2)(2-SB)(2)(H(2)O)(6)](2-) subunit. The ox ligand acts as a bridge, linking the binuclear [Gd(2)(2-SB)(2)(H(2)O)(6)](2-) subunits into a one-dimensional chain structure parallel to the b axis. Furthermore, extensive O-H···O hydrogen bonds connect the chains into a three-dimensional supramolecular architecture.
RESUMO
Attractive results have been achieved with small-molecule target-based drugs in the anticancer field; however, enhancing their treatment effect and solving the problem of drug resistance remain key concerns worldwide. Inspired by the specific affinity of gefitinib for tumour cells and the strong oxidation capacity of singlet oxygen, we combined a chemically generated singlet oxygen moiety with the small-molecule targeted drug gefitinib to improve its anticancer effect. We designed and synthesised a novel compound (Y5-1), in which a small-molecule targeted therapy agent (gefitinib) and a singlet oxygen (provided by an inâ vitro photodynamic reaction) thermally controlled releasing moiety are covalently conjugated. We demonstrated that the introduction of the singlet oxygen thermally controlled releasing moiety enhanced the anticancer activities of gefitinib. The results of this study are expected to provide a novel strategy to enhance the effect of chemotherapy drugs on drug-resistant cell lines.