pPB peptide-mediated siRNA-loaded stable nucleic acid lipid nanoparticles on targeting therapy of hepatic fibrosis.
Mol Pharm. 2017 Nov 17;:
Authors: Jia Z, Gong Y, Pi Y, Liu X, Gao L, Kang L, Wang J, Yang F, Tang J, Lu W, Li Q, Zhang W, Yan Z, Yu L
Hepatic fibrosis is a necessary process in the development of liver diseases such as hepatic cirrhosis and its complications, which has become a serious threat to human health. Currently, antifibrotic drug treatment is ineffective, and one of the reasons should be the lack of liver targeting ability. In this report, polypeptide pPB modified stable nucleic acid lipid nanoparticles (pPB-SNALP) were prepared to selectively deliver siRNAs against heat shock protein 47 (HSP47) to liver for targeted therapy of hepatic fibrosis. First, siRNA sequences with high silencing efficiency were screened based on siRNA transfection efficacy. Then, pPB-SNALP were prepared, which showed a narrow size distribution with a diameter in the range of 110-130 nm and a neutral z-potential of 0 mV. As evidenced by the in vitro and in vivo targeting study, compared with unmodified SNALP, pPB-SNALP showed increased uptake by LX-2 cells and primary hepatic stellate cells (HSC) of mice in vitro, and showed increased liver distribution and HSC uptake in vivo. In addition, pPB-SNALP also exhibited an enhanced inhibitory effect on TAA-induced hepatic fibrosis mice with high gp46 mRNA expression in vivo. In summary, our results demonstrated that pPB-SNALP is an effective liver-targeted delivery system. This study could lay a good foundation for the targeted gene therapy of hepatic fibrosis.
PMID: 29148802 [PubMed - as supplied by publisher]
Ambient Aqueous Synthesis of Ultrasmall Ni0.85Se Nanoparticles for Non-Invasive Photoacoustic Imaging and Combined Photothermal-Chemo Therapy of Cancer.
ACS Appl Mater Interfaces. 2017 Nov 17;:
Authors: Wang X, Li F, Yan X, Ma Y, Miao Z, Dong L, Chen H, Lu Y, Zha Z
Big size induced long-term retention in the body has hampered the translational applications of many reported nanomedicine. Herein, we reported a multifunctional theranostic agent composed of ultrasmall polyacrylic acid functionalized Ni0.85Se nanoparticles (PAA-Ni0.85Se NPs), which were successfully obtained through a facile ambient aqueous precipitation strategy. Without exhibiting any noticeable toxicity, the as-prepared PAA-Ni0.85Se NPs (average diameter of 6.40 ± 1.89 nm) showed a considerable absorption in near-infrared (NIR) region and high photothermal conversion efficiency (PTCE) of 54.06%, which could induce remarkable photoacoustic signals for tumor imaging and heat for localized ablation of cancerous cells upon exposure to NIR light. Notably, the ultrasmall PAA-Ni0.85Se NPs, unlike conventional nanomaterials with larger sizes, showed reasonable body clearance within 8 h after intravenous injection. Furthermore, ascribed to protonation process of amino groups in DOX molecules and carboxyl groups in PAA molecules at acidic microenvironment, the drug-loaded (doxorubicin hydrochloride, DOX•HCl) PAA-Ni0.85Se NPs (PAA-Ni0.85Se-DOX NPs) revealed promoted drug release at acidic pH, which could be useful for acidic tumor microenvironment responsive drug delivery. Evident from the results of cell-killing assay in vitro and tumor treatment study in vivo, PAA-Ni0.85Se-DOX NPs exhibited evident synergistic effects on killing 4T1 breast cancer cells. Thus, this study presents a multifunctional theranostic agent composed of ultrasmall PAA-Ni0.85Se NPs for potential cancer treatment without long-term toxicity concerns.
PMID: 29148694 [PubMed - as supplied by publisher]
Effect of Tirapazamine, Metformin or Mild Hyperthermia on Recovery From Radiation-Induced Damage in Pimonidazole-Unlabeled Quiescent Tumor Cells.
World J Oncol. 2017 Oct;8(5):137-146
Authors: Masunaga SI, Tano K, Sanada Y, Sakurai Y, Tanaka H, Suzuki M, Kondo N, Watanabe T, Takata T, Maruhashi A, Ono K
Background: The aim of the study was to examine the effect of tirapazamine (TPZ) on recovery from radiation-induced damage in pimonidazole-unlabeled quiescent (Q) tumor cells compared with that of metformin (Met) or mild temperature hyperthermia (MTH).
Methods: Proliferating (P) cells in EL4 tumors were labeled by continuous 5-bromo-2'-deoxyuridine (BrdU) administration. Tumors received γ-rays at 1 h after pimonidazole administration followed by Met or TPZ treatment or MTH. Twenty-four hours later, the responses of Q and total (P + Q) cells and those of the pimonidazole-unlabeled cells were assessed with micronucleation and apoptosis frequencies using immunofluorescence staining for BrdU and apoptosis frequency using immunofluorescence staining for pimonidazole, respectively.
Results: With γ-rays only, the pimonidazole-unlabeled cell fraction showed significantly enhanced radio-sensitivity compared with the whole cell fraction more remarkably in Q than total cells. However, a significantly greater decrease in radio-sensitivity in the pimonidazole-unlabeled than the whole cell fraction, evaluated using a delayed assay, was more clearly observed in Q than total cells. Post-irradiation MTH or Met treatment more clearly repressed the decrease in radio-sensitivity in the Q than total cells. Post-irradiation TPZ administration produced a large radio-sensitizing effect on both total and Q cells, especially on Q cells. In pimonidazole-unlabeled cell fractions in both total and Q cells, TPZ suppressed the reduction in sensitivity much more efficiently than MTH or Met without any radio-sensitizing effect.
Conclusion: Post-irradiation TPZ administration has the potential to both suppress recovery from radiation-induced damage and enhance the radio-sensitivity both in total and Q tumor cells. Post-irradiation TPZ administration may be useful for controlling tumors.
PMID: 29147450 [PubMed]
Targeted therapy of gastroenteropancreatic neuroendocrine tumours: preclinical strategies and future targets.
Endocr Connect. 2017 Nov 16;:
Authors: Aristizabal Prada ET, Auernhammer CJ
Molecular targeted therapy of advanced neuroendocrine tumours (NETs) of the gastroenteropancreatic (GEP) system currently encompasses approved therapy with the mTOR-inhibitor everolimus and the multi-tyrosinkinase inhibitor sunitinib. However clinical efficacy of these treatment strategies is limited by low objective response rates and limited progression free survival due to tumor resistance. Further novel strategies for molecular targeted therapy of NETs of the GEP-system are needed. This paper reviews preclinical research models and signaling pathways in NETs of the GEP-system. Preclinical and early clinical data on putative novel targets for molecular targeted therapy of NETs of the GEP-system are discussed, including PI3K, Akt, mTORC1/mTORC2, GSK3, c-Met, Ras-Raf-MEK-ERK, embryogenic pathways (Hedgehog, Notch, Wnt/beta-catenin, TGF-β Signaling and SMAD proteins), tumor suppressors and cell cycle regulators (p53, cyclin dependent kinases (CDK) CDK4/6, CDK inhibitor p27, retinoblastoma protein (Rb) ), heat shock protein HSP90, Aurora kinase, Src kinase family, focal adhesion kinase (FAK) and epigenetic modulation by histone deacetylase inhibitors (HDAC).
PMID: 29146887 [PubMed - as supplied by publisher]
Current practice and usual care of major cervical disorders in Korea: A cross-sectional study of Korean health insurance review and assessment service national patient sample data.
Medicine (Baltimore). 2017 Nov;96(46):e8751
Authors: Choi AR, Shin JS, Lee J, Lee YJ, Kim MR, Oh MS, Lee EJ, Kim S, Kim M, Ha IH
Neck pain is a highly common condition and is the 4th major cause of years lived with disability. Previous literature has focused on the effect of specific treatments, and observations of actual practice are lacking to date. This study examined Korean health insurance review and assessment service (HIRA) claims data to the aim of assessing prevalence and comparing current medical practice and costs of cervical disorders in Korea.Current practice trends were determined through assessment of prevalence, total expenses, per-patient expense, average days in care, average days of visits, sociodemographic characteristics, distribution of medical costs, and frequency of treatment types of high frequency cervical disorders (cervical sprain/strain, cervical intervertebral disc displacement [IDD], and cervicalgia).Although the number of cervical IDD patients was few, total expenses, per-patient expense, average days in care, and average days of visits were highest. The proportion of women was higher than men in all 3 groups with highest prevalence in the ≥50s middle-aged population for IDD compared to sprain/strain. Primary care settings were commonly used for ambulatory care, of which approximately 70% chose orthopedic specialist treatment. In analysis of medical expenditure distribution, costs of visit (consultation) (22%-34%) and physical therapy (14%-16%) were in the top 3 for all 3 disorders. Although heat and electrical therapies were the most frequently used physical therapies, traction use was high in the cervical IDD group. In nonnarcotics, aceclofenac and diclofenac were the most commonly used NSAIDs, and pethidine was their counterpart in narcotics.This study investigated practice trends and cost distribution of treatment regimens for major cervical disorders, providing current usage patterns to healthcare policy decision makers, and the detailed treatment reports are expected to be of use to clinicians and researchers in understanding current usual care.
PMID: 29145327 [PubMed - in process]
Albumin-coordinated assembly of clearable platinum nanodots for photo-induced cancer theranostics.
Biomaterials. 2017 Oct 20;154:248-260
Authors: Tang Y, Yang T, Wang Q, Lv X, Song X, Ke H, Guo Z, Huang X, Hu J, Li Z, Yang P, Yang X, Chen H
Photoactive noble metal nanoparticles are of increasing importance toward personalized cancer therapy in the field of precision nanomedicine. A critical challenge remains in the exploration of clinically potential noble metal nanoparticles for highly efficient cancer theranostics. Here, we introduce albumin-coordinated assembly of clearable Pt nanodots (Pt-NDs) with monodisperse nanostructure as high-performance theranostic agents for imaging-guided photothermal tumor ablation. We precisely manipulate the reduction and growth of tetravalent Pt ions into ultrasmall nanodots through albumin-directed growth kinetics, thereby leading to the synthesis of monodisperse 6.7 nm Pt-NDs with albumin molecules as the corona. Pt-NDs exhibit the surface plasmon resonance at 225 nm with enhanced near-infrared (NIR) absorbance, ideal resistance to photo-bleaching, distinct photoacoustic and X-ray signals, as well as remarkable photothermal effect through non-radiative relaxation under NIR light irradiation. In particular, Pt-NDs possess preferable tumor accumulation, and effective in vivo excretory capability. Thus, these nanodots promote preferable in vivo microscopic photoacoustics and spatially anatomic CT imaging with enhanced contrast, as well as potent hyperthermia-mediated tumor ablation. These findings represent a facile and general approach to fabricate high-performance noble metal nanostructures with clinical potential for cancer theranostics.
PMID: 29144983 [PubMed - as supplied by publisher]