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Ph in cancer therapy

Dunwan Zhu, Fan Fan, Chenlu Huang, Zhiming Zhang, Yu Qin, Li Lu, Hai Wang, Xu Jin, Hanxue Zhao, Hu Yang, Chao Zhang, Jun Yang, Zhipeng Liu, Hongfan Sun, Xigang Leng, Deling Kong, Linhua Zhang
The combination of chemotherapy and photothermaltherapy (PTT) via stimuli-responsive nanovesicles has great potential in tumor treatment. In the present study, bubble-generating polymersomes, which can generate bubbles in response to low pH or hyperthermia, were fabricated to simultaneously encapsulate chemotherapeutic drug and photosensitizing agent for the synergistic chemo-photothermal tumor therapy. Photosensitizer indocyanine green (ICG) was encapsulated into the bilayer of polymersomes formed by amphiphilic triblock copolymer PCL8000 -PEG8000 -PCL8000 through thin film re-hydration method, while chemotherapeutic doxorubicin (DOX) was loaded into the hydrophilic lumen using a transmembrane ammonium bicarbonate gradient loading procedure...
May 21, 2018: Acta Biomaterialia
Yu Cao, Min Chen, Dehua Tang, Hongli Yan, Xiwei Ding, Fan Zhou, Mingming Zhang, Guifang Xu, Weijie Zhang, Shu Zhang, Yuzheng Zhuge, Lei Wang, Xiaoping Zou
Proton pump inhibitors (PPIs) play a role in antitumor activity, with studies showing specialized impacts of PPIs on cancer cell apoptosis, metastasis, and autophagy. In this study, we demonstrated that pantoprazole (PPI) increased autophagosomes formation and affected autophagic flux depending on the pH conditions. PPI specifically elevated SQSTM1 protein levels by increasing SQSTM1 transcription via NFE2L2 activation independent of the specific effect of PPI on autophagic flux. Via decreasing proteasome subunits expression, PPI significantly impaired the function of the proteasome, accompanied by the accumulation of undegraded poly-ubiquitinated proteins...
May 22, 2018: Cell Death & Disease
Yiwen Li, Huailin Yang, Jiuxu Yao, Haiyang Yu, Xin Chen, Peng Zhang, Chunsheng Xiao
An amphiphilic biodegradable prodrug (PLG-g-mPEG/CPT) was synthesized by conjugating disulfide-containing camptothecin (CPT) to poly(L-glutamic acid)-graft-methoxy poly(ethylene glycol) (PLG-g-mPEG) through esterification reaction. The amphiphilic prodrugs could self-assemble into micellar nanoparticles and encapsulate doxorubicin (DOX) in aqueous solution at pH 7.4. The treatment of the nanoparticles with reducing glutathione (GSH) at cytosolic concentration (10 mM) significantly promoted the in vitro dual release of DOX and CPT from the micelles...
May 17, 2018: Colloids and Surfaces. B, Biointerfaces
Xiaoyun Wang, Fengbo Wu, Guoyou Li, Nan Zhang, Xiangrong Song, Yu Zheng, Changyang Gong, Bo Han, Gu He
Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer, and one therapeutic approach is to target both the AMPK and autophagy pathways in order to synergistically promote programmed cell death. Here, a series of amphiphilic, lipid-modified cell-penetrating peptides were synthesized and allowed to self-assemble into micelles loaded with the AMPK activator narciclasine (Narc) and short interfering RNA targeting the unc-51-like kinase 1 (siULK1). The size of these micelles, their efficiency of transfection into cells, and their ability to release drug or siRNA cargo in vitro were pH-sensitive, such that drug release was facilitated in the acidic microenvironment of the tumor...
May 19, 2018: Acta Biomaterialia
Yang Li, Huabing Zhang, Yilin Chen, Jinyuan Ma, Jinyan Lin, Yinying Zhang, Zhongxiong Fan, Guanghao Su, Liya Xie, Xuan Zhu, Zhenqing Hou
Combinational cancer therapy has been considered as a promising strategy to achieve synergetic therapeutic effects and suppression of multidrug resistance. Herein, we adopted a combination of methotrexate (MTX), an antimetabolite acting on cytoplasm, and 10-hydroxycamptothecin (HCPT), an alkaloid acting on nuclei, to treat cancer. Given the different solubilities, membrane permeabilities, and anticancer mechanisms of both drugs, we developed a dual-targeting delivery system based on 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-hyaluronic acid (a principal ligand of CD44 receptors)-MTX (a selective ligand of folate receptors) nanoparticles, which was exploited to carry HCPT-MTX conjugate for synergistically boosting dual-drug co-delivery...
May 22, 2018: Biomaterials Science
Xi Hu, Fangyuan Li, Shuying Wang, Fan Xia, Daishun Ling
Nanoassembly technology has emerged as a powerful tool for targeted drug delivery and provides a basis for fabricating medical theranostic nanosystems. However, it is extremely difficult to concentrate nanoparticles at tumor sites, and the poor target-to-background ratio undoubtedly obstructs the accurate diagnosis and effective therapy of cancerous tissues. Importantly, the addition of biological stimulus-responsive groups to nanoassembly systems can enable a biological stimulus-driven assembly-disassembly mutual switch or structural composition/conformation change, thereby amplifying the imaging signal and/or enhancing the therapeutic effect...
May 21, 2018: Advanced Healthcare Materials
Mei Chen, Zhide Guo, Qinghua Chen, Jingping Wei, Jingchao Li, Changrong Shi, Duo Xu, Dawang Zhou, Xianzhong Zhang, Nanfeng Zheng
Radiolabeled nanoparticles (NPs), taking advantage of nanotechnology and nuclear medicine, have shown attractive potential for cancer diagnosis and therapy. However, the high background signal in the liver and long-term toxic effects of radioisotopes caused by the nonselective accumulation of radiolabeled nanoparticles in organs have become the major challenges. Here, we report a pH-sensitive multifunctional theranostic platform with radiolabeled Pd nanosheets through a simple mixture of ultra-small Pd nanosheets and radioisotopes utilizing the strong adsorption of 131 I and 125 I on their surfaces (denoted as 131 I-Pd-PEG or 125 I-Pd-PEG)...
May 14, 2018: Chemical Science
Linhua Zhang, Yu Qin, Zhiming Zhang, Fan Fan, Chenlu Huang, Li Lu, Hai Wang, Xu Jin, Hanxue Zhao, Deling Kong, Chun Wang, Hongfan Sun, Xigang Leng, Dunwan Zhu
The combination of chemotherapy and photothermal therapy in multifunctional nanovesicles has emerged as a promising strategy to improve cancer therapeutic efficacy. Herein, we designed new pH/reduction dual-responsive and folate decorated polymeric micelles (FA Co-PMs) as theranostic nanocarrier to co-encapsulate doxorubicin (DOX) and indocyanine green (ICG) for targeted NIR imaging and chemo-photothermal combination therapy. The Co-PMs exhibited nano-sized structure (∼100 nm) with good monodispersity, high encapsulation efficiency of both ICG and DOX, triggered DOX release in response to acid pH and reduction environment, and excellent temperature conversion with laser irradiation...
May 16, 2018: Acta Biomaterialia
Cheong A Choi, Jung Eun Lee, Zihnil Adha Islamy Mazrad, Young Kwang Kim, Insik In, Ji Hoon Jeong, Sung Young Park
We described fluorescence resonance energy transfer for pH/redox-activatable fluorescent carbon dot (FNP) to realize "off-on" switched imaging-guided controllable photothermal therapy (PTT). The FNP is a carbonized self-crosslinked polymer that allows IR825 loading (FNP[IR825]) via hydrophobic interactions in cancer therapy. The capability for fluorescence bioimaging was achieved via the internalization of FNP(IR825) into tumor cells, wherein glutathione (GSH) disulfide bonds were reduced and benzoic imine were cleaved under acidic conditions...
May 18, 2018: ChemMedChem
Jinhwan Kim, Changshin Jo, Won-Gwang Lim, Sungjin Jung, Yeong Mi Lee, Jun Lim, Haeshin Lee, Jinwoo Lee, Won Jong Kim
Tumors are 3D, composed of cellular agglomerations and blood vessels. Therapies involving nanoparticles utilize specific accumulations due to the leaky vascular structures. However, systemically injected nanoparticles are mostly uptaken by cells located on the surfaces of cancer tissues, lacking deep penetration into the core cancer regions. Herein, an unprecedented strategy, described as injecting "nanoparticle-loaded nanoparticles" to address the long-lasting problem is reported for effective surface-to-core drug delivery in entire 3D tumors...
May 18, 2018: Advanced Materials
Zhengze Lu, Yang Long, Xingli Cun, Xuhui Wang, Jianping Li, Ling Mei, Yiliang Yang, Man Li, Zhirong Zhang, Qin He
Cancer-related inflammation can promote tumorigenesis, tumor growth and tumor metastasis in many types of cancers. Therefore, inhibiting cancer-related inflammation significantly improves cancer therapy. It has been reported that metformin (MET) inhibits the nuclear translocation of nuclear factor-κB (NF-κB), a key factor in cancer-related inflammation. However, the short half-life and the lack of tumor targeting limit the anti-inflammatory efficacy of MET in vivo. Herein, using pH-sensitive imine bonds, MET and the chemotherapy drug doxorubicin (DOX) were loaded onto size-shrinkable RGD-DGL-GNP nanoparticles (RDG NPs) for combination therapy...
May 17, 2018: Nanoscale
Qiang Liu, Jiao Wang, Linnan Yang, Xiaofei Xia, Mei Wang, Shengguang Chen, Rongrong Zhu, Qingxiu Wang, Xianzheng Wu, Shilong Wang
In this study, a promising drug nano-carrier system consisting of mono-dispersed and pH sensitive carboxylated chitosan-hollow mesoporous silica nanoparticles (Ccs-HMSNs) suitable for the treatment of malignant cells was synthesised and investigated. At neutral pH, the Ccs molecules are orderly aggregated state, which could effectively hinder the release of loaded drug molecules. However, in slightly acidic environment, Ccs chains are heavily and flexibly entangled in gel state, which would enhance the subsequent controlled release of the loaded drug...
June 2018: IET Nanobiotechnology
Wen Jing Yang, Peng Zhou, Lijun Liang, Yanpeng Cao, Junqin Qiao, Xiaohui Li, Zhaogang Teng, Lianhui Wang
Drug combination therapies employing dual drug delivery systems offer an effective approach to reduce disadvantages of single drug therapy, such as high dose and easy generation of drug resistance. Herein, a dual drug delivery system based on nanogel-incorporated injectable hydrogel (NHG) was designed for sequentially local delivery of combretastatin-A4 phosphate (CA4P) and doxorubicin (DOX) for antiangiogensis and anticancer combination therapy. The injectable hydrogel was prepared for loading and quick release of hydrophilic drug CA4P, while the pH and redox stimuli-responsive nanohydrogels were incorporated into the injectable hydrogel by pH-responsive boronate ester bond for sustained long-term DOX delivery...
May 16, 2018: ACS Applied Materials & Interfaces
Arpita Basu, Sarmishtha Ray, Supriyo Chowdhury, Arnab Sarkar, Deba Prasad Mandal, Shamee Bhattacharjee, Surekha Kundu
Biosynthesis of gold nanoparticles of distinct geometric shapes with highly functional protein coats without additional capping steps is rarely reported. This study describes green synthesis of protein-coated gold nanoparticles for the first time from the edible, mycorrhizal fungus Tricholoma crassum (Berk.) Sacc. The nanoparticles were of the size range 5-25 nm and of different shapes. Spectroscopic analysis showed red shift of the absorption maxima with longer reaction period during production and blue shift with increase in pH...
May 16, 2018: Nanoscale Research Letters
Jia Zhou, Tianliang Li, Chunlei Zhang, Junyuan Xiao, Daxiang Cui, Yingsheng Cheng
Multifunctional nanoplatforms have been developed into advanced drug delivery systems for cancer therapy. In this study, we report a charge-switchable nanocapsule with multistage pH-responsive behaviors. First, DOX-encapsulated and oleylamine-embedded hollow structures with a diameter of 132 ± 21 nm are prepared via the double emulsion method. Subsequently, the hollow structures are encompassed by Gd-DTPA-, chlorin e6 (Ce6)-, and folate (FA)-modified BSA to form tumour-targeted, dual NIR/MR imaging-guided and chemo-photodynamic therapeutic nanoplatforms...
May 15, 2018: Nanoscale
K C Ajithkumar, K Pramod
Doxorubicin is a broad spectrum anticancer antibiotic that possesses toxic effects such as cardiomyopathy, that even lead to congestive heart failure. Thus, the development of a new bio-inspired system is required, that retain the advantageous effect of doxorubicin while retarding the side effects. Hence, a system was developed that we describe 'doxorubicin-DNA adduct entrenched artificial virus encased in polypeptide complex'. The drug-DNA adduct (DDA) was prepared by a formaldehyde mediated reaction. A simple chloroform extraction method for the separation of DDA was developed...
August 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
Junyi Zhou, Haian Xu, Zaizai Tong, Yuhui Yang, Guohua Jiang
Herein, dual stimuli-responsive compound vesicles were constructed based on host-guest interaction between a water-soluble pillar[6]arene (WP6) and an amphiphilic azobenzene-containing block copolymers (BCP). Reversible morphological transformation between compound vesicles and solid aggregates was achieved by repeated pH- and photo-stimuli. These compound vesicles were then applied in the controlled release of water-soluble anticancer drug, doxorubicin hydrochloride (DOX · HCl). Upon external stimuli, the DOX · HCl displayed a faster release rate than that without stimuli...
August 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
Kamran Iravani Kashkouli, Masoud Torkzadeh-Mahani, Elaheh Mosaddegh
In the present study, Fe3 O4 /chitosan biopolymer grafted to a novel organosilane modified 5-amino-1H-tetrazole, a kind of drug intermediate, was successfully synthesized by chemical modification technique and evaluated as a high potential carrier of gene delivery. The loading capacity was evaluated, and in vitro release of nanocarrier was assessed using the dialysis method. The transfection efficiency of plasmid was optimal at an N/P ratio of 3. The chemically modified chitosan showed no inherent toxicity toward the cells...
August 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
Yushen Jin, Xin Yang, Jie Tian
Early identification and treatment of hepatocellular carcinoma is very important for improving the prognosis and survival rate of the patient. To enhance the visualization and treatment efficiency of HCC, a theranostic agent has been developed that combines photoacoustic/fluorescence imaging with photothermal therapy for cancer. We report the synthesis of multifunctional theranostic SP94-modified polypyrrole (PPy)-BSA-ICG nanoparticles by a simple method. The multifunctional theranostic agent helped to combine two modes of imaging modalities, i...
May 10, 2018: Nanoscale
Barbara Hersant, Mounia SidAhmed-Mezi, Yazid Belkacemi, Franklin Darmon, Sylvie Bastuji-Garin, Gabrielle Werkoff, Romain Bosc, Jeremy Niddam, Oana Hermeziu, Simone La Padula, Jean Paul Meningaud
OBJECTIVE: Approximately 50% to 70% of breast cancer survivors are affected by one or more symptoms of vulvovaginal atrophy (VVA). For those who cannot take hormone therapy, autologous platelet-rich plasma combined with hyaluronic acid (A-PRP-HA) may provide a new alternative therapy for the treatment of VVA in postmenopausal women with history of breast cancer. METHODS: We enrolled 20 postmenopausal breast cancers survivors with VVA and a score of <15 on the Gloria Bachman Vaginal Health Index (VHI) comprised of five items including: vaginal pH, elasticity, fluid volume (secretions), epithelial integrity, and moisture...
May 7, 2018: Menopause: the Journal of the North American Menopause Society
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