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Targeted drug delivery

M S Eng, J Kaur, L Prasmickaite, B Ø Engesæter, A Weyergang, E Skarpen, K Berg, M G Rosenblum, G M Mælandsmo, A Høgset, S Ferrone, P K Selbo
Triple-negative breast cancer (TNBC) and malignant melanoma are highly aggressive cancers that widely express the cell surface chondroitin sulfate proteoglycan 4 (CSPG4/NG2). CSPG4 plays an important role in tumor cell growth and survival and promotes chemo- and radiotherapy resistance, suggesting that CSPG4 is an attractive target in cancer therapy. In the present work, we applied the drug delivery technology photochemical internalization (PCI) in combination with the novel CSPG4-targeting immunotoxin 225...
March 22, 2018: Photochemical & Photobiological Sciences
Qingfen Yu, Sameh Othman, Sabyasachi Dasgupta, Thorsten Auth, Gerhard Gompper
Nanoparticles in biological systems encounter lipid-bilayer membranes as barriers. They interact with plasma membranes, membranous organelles, such as the endoplasmic reticulum and the Golgi apparatus, the nucleus, and intracellular and extracellular vesicles, such as autophagosomes, lysosomes, and exosomes. Extracellular vesicles have recently attracted particular attention, as they are involved in the transmission of biological signals and as regulators for biological processes. For example, exosomes, small vesicles containing proteins, mRNA, and miRNA, that are released by cells into the extracellular environment, have been suggested to participate in tumor metastasis...
March 22, 2018: Nanoscale
Zhilan Ye, Tao Zhang, Wenshan He, Honglin Jin, Cuiwei Liu, Zhe Yang, Jinghua Ren
Despite promising in-vitro evidence for effective glioblastoma treatment, most drugs are hindered from entering the central nervous system due to the presence of the blood-brain barrier (BBB). Thus, successful modification of drug delivery and novel therapeutic strategies are needed to overcome this obstacle. Extracellular vesicles (EVs), cell-derived membrane-encapsulated structures with diameters ranging from 50-1000 nm, have been explored as drug delivery system to deliver their cargo to the brain tissue...
March 22, 2018: ACS Applied Materials & Interfaces
Gella Maelys Ngandeu Neubi, Yaw Opoku-Damoah, Xiaochen Gu, Yue Han, Jianping Zhou, Yang Ding
The quest for an ideal cancer treatment has led to the exploration of a variety of platforms to facilitate highly desirable and efficient drug delivery. As most anticancer drugs possess therapeutic potency to destroy tumor cells, there is a need to steer the compounds to their required sites using site-specific drug delivery vehicles. This has inspired the investigation of various natural particulates and biomaterials for the purpose. Bio-inspired platforms that directly mimic natural components in the body have demonstrated their ability to serve as one of the most versatile and innovative drug delivery systems in cancer therapy and diagnosis...
March 22, 2018: Biomaterials Science
Xingmei Duan, Minjie Mu, Junfeng Yan, Lan Bai, Lei Zhong, Yuxuan Zhu, Haixia Pan, Mei Zhang, Jianyou Shi
Background: The newly synthesized Aurora-A kinase inhibitor XY-4 is a potential anti-cancer agent, but its hydrophobicity and limited efficiency restrict further application. Nanotechnology based combined therapy provides an optimized strategy for solving these issues. Methods: In this study, the newly synthesized Aurora-A kinase inhibitor XY-4 and Bcl-xl targeted siRNA were co-delivered by cationic liposomes, creating an injectable co-delivery formulation. The anti-cancer ability and mechanisms of XY-4/Bcl-xl siRNA co-loaded cationic liposomes were studied both in vitro and in vivo...
2018: International Journal of Nanomedicine
Dereje Kebebe, Yuanyuan Liu, Yumei Wu, Maikhone Vilakhamxay, Zhidong Liu, Jiawei Li
Cancer has become one of the leading causes of mortality globally. The major challenges of conventional cancer therapy are the failure of most chemotherapeutic agents to accumulate selectively in tumor cells and their severe systemic side effects. In the past three decades, a number of drug delivery approaches have been discovered to overwhelm the obstacles. Among these, nanocarriers have gained much attention for their excellent and efficient drug delivery systems to improve specific tissue/organ/cell targeting...
2018: International Journal of Nanomedicine
Jiajiang Xie, Zhongxiong Fan, Yang Li, Yinying Zhang, Fei Yu, Guanghao Su, Liya Xie, Zhenqing Hou
Aim: We designed acid-labile methotrexate (MTX) targeting prodrug self-assembling nanoparticles loaded with curcumin (CUR) drug for simultaneous delivery of multi-chemotherapeutic drugs and combination cancer therapy. Methods: A dual-acting MTX, acting as both an anticancer drug and as a tumor-targeting ligand, was coupled to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[aldehyde(polyethylene glycol)-2000] via Schiff's base reaction. The synthesized prodrug conjugate (DSPE-PEG-Imine-MTX) could be self-assembled into micellar nanoparticles (MTX-Imine-M) in aqueous solution, which encapsulated CUR into their core by hydrophobic interactions (MTX-Imine-M-CUR)...
2018: International Journal of Nanomedicine
Conglian Yang, Tingting Wu, Yuting Qin, Yan Qi, Yu Sun, Miao Kong, Xue Jiang, Xianya Qin, Yaqi Shen, Zhiping Zhang
Background: Doxorubicin (DOX) is an effective chemotherapeutic agent but severe side effects limit its clinical application. Nanoformulations can reduce the toxicity while still have various limitations, such as complexity, low drug loading capability and excipient related concerns. Methods: An amphiphilic conjugate, doxorubicin-dichloroacetate, was synthesized and the corresponding nanoparticles were prepared. The in vitro cytotoxicity and intracellular uptake, in vivo imaging, antitumor effects and systemic toxicities of nanoparticles were carried out to evaluate the therapeutic efficiency of tumor...
2018: International Journal of Nanomedicine
Laura Saludas, Simón Pascual-Gil, Filippo Roli, Elisa Garbayo, María J Blanco-Prieto
The capacity of the heart to heal after a myocardial infarction is not enough to restore normal cardiac function. Fortunately, delivery of therapeutics such as stem cells, growth factors, exosomes and small interfering ribonucleic acid (siRNA), among other bioactive molecules, has been shown to enhance heart repair and improve cardiac function. Furthermore, new delivery systems for these therapeutic agents have enhanced their regenerative and cardioprotective potential. In particular, nano- and microparticles (NPs and MPs) are promising...
April 2018: Maturitas
Yoon Jin Cha, Eun-Sol Kim, Ja Seung Koo
Amino acid transporters are membrane transport proteins, most of which are members of the solute carrier families. Amino acids are essential for the survival of all types of cells, including tumor cells, which have an increased demand for nutrients to facilitate proliferation and cancer progression. Breast cancer is the most common malignancy in women worldwide and is still associated with high mortality rates, despite improved treatment strategies. Recent studies have demonstrated that the amino acid metabolic pathway is altered in breast cancer and that amino acid transporters affect tumor growth and progression...
March 19, 2018: International Journal of Molecular Sciences
Rebecca M Nisbet, Jürgen Götz
Accumulation of the peptide amyloid-β (Aβ) and the protein tau in Alzheimer's disease (AD) brains is a gradual process that involves the post-translational modification and assembly of monomeric forms into larger structures that eventually form fibrillar inclusions. This process is thought to both drive and initiate AD. However, why the axonally enriched tau in the course of AD accumulates in the somatodendritic domain is not fully understood. We discuss new data that provide a possible explanation that involves de novo protein synthesis, induced by Aβ and mediated through the kinase Fyn...
March 16, 2018: Journal of Alzheimer's Disease: JAD
Mark Sherman, Lydia Contreras
Recent advances in computational and experimental methods have led to novel avenues for therapeutic development. Utilization of nucleic acids as therapeutic agents and/or targets has been recently gaining attention due to their potential as high-affinity, selective molecular building blocks for various therapies. Notably, development of computational algorithms for predicting accessible RNA binding sites, identifying therapeutic target sequences, modeling delivery into tissues, and designing binding aptamers have enhanced therapeutic potential for this new drug category...
March 18, 2018: Current Opinion in Biotechnology
Chrysovalantis Voutouri, Triantafyllos Stylianopoulos
Hyaluronan is abundant in the extracellular matrix of many desmoplastic tumors and determines in large part the tumor biochemical and mechanical microenvironment. Additionally, it has been identified as one of the major physiological barriers to the effective delivery of drugs to solid tumors and its targeting with the use of pharmaceutical agents has shown to decompress tumor blood vessels, and thus improve tumor perfusion and efficacy of cytotoxic drugs. In this study, we investigated the contribution of hyaluronan to the accumulation of mechanical forces in tumors...
2018: PloS One
Mahtab Alam, Abul Kalam Najmi, Iqbal Ahmad, Farhan Jalees Ahmad, Md Jawaid Akhtar, Syed Sarim Imam, Mohd Akhtar
The study performed molecular docking, formulated, characterized thymoquinone (TQ) loaded solid lipid nano particles (TQSLN) and exhibited comparative antidepressant activity. TQ loaded nano lipid formulations were prepared by solvent injection methods and characterize for different in-vitro parameters. The optimized formulation was evaluated for depression using unpredictable chronic mild stress (UCMS) model for a period of six weeks. TQSLN was assessed in modified forced swim test (MFST), tail suspension test (TST), locomotor activity followed by biochemical parameters such as monoaminesand brain derived neurotrophic factor (BDNF)...
March 21, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Sudipta Senapati, Arun Kumar Mahanta, Sunil Kumar, Pralay Maiti
Although conventional chemotherapy has been successful to some extent, the main drawbacks of chemotherapy are its poor bioavailability, high-dose requirements, adverse side effects, low therapeutic indices, development of multiple drug resistance, and non-specific targeting. The main aim in the development of drug delivery vehicles is to successfully address these delivery-related problems and carry drugs to the desired sites of therapeutic action while reducing adverse side effects. In this review, we will discuss the different types of materials used as delivery vehicles for chemotherapeutic agents and their structural characteristics that improve the therapeutic efficacy of their drugs and will describe recent scientific advances in the area of chemotherapy, emphasizing challenges in cancer treatments...
2018: Signal Transduction and Targeted Therapy
Kurt Wood, Myron R Szewczuk, Dérick Rousseau, Ronald J Neufeld
Pickering emulsions are colloidal dispersions stabilized by particles that either migrate to, or are formed at, the oil-water interface during emulsification. Here, we fabricated and characterized Pickering water-in-oil emulsions where molten glycerol monostearate crystallized at the surface of micron-sized water droplets and formed protective solid shells. We tested this emulsion as a reservoir delivery platform for the sustained release of low molecular weight hydrophilic molecules including sodium chloride (NaCl) and sodium citrate as model compounds, and the therapeutic oseltamivir phosphate (OP), the delivery of which was the ultimate goal of this research...
February 27, 2018: Oncotarget
Zheng Wei, Xiteng Yin, Yu Cai, Wenguang Xu, Chuanhui Song, Yufeng Wang, Jingwei Zhang, An Kang, Zhiyong Wang, Wei Han
Background: Tumor microenvironment plays an important role in the chemoresistance of oral squamous cell carcinoma (OSCC). Hypoxia in the microenvironment is one of the important factors that contributes to OSCC chemoresistance; therefore overcoming hypoxia-mediated chemoresistance is one of the great challenges in clinical practice. Methods: In this study, we developed a drug delivery system based on Pt-loaded, polyethylene glycol-modified graphene quantum dots via chemical oxidation and covalent reaction...
2018: International Journal of Nanomedicine
Celina Yang, Kyle Bromma, Devika Chithrani
Optimizing the interface between nanoparticles (NPs) and the biological environment at various levels should be considered for improving delivery of NPs to the target tumor area. For NPs to be successfully delivered to cancer cells, NPs needs to be functionalized for circulation through the blood vessels. In this study, accumulation of Polyethylene Glycol (PEG) functionalized gold nanoparticles (GNPs) was first tested using in vitro monolayer cells and multilayer cell models prior to in vivo models. A diameter of 10 nm sized GNP was selected for this study for sufficient penetration through tumor tissue...
March 20, 2018: Cancers
Antonio Lopalco, Annalisa Cutrignelli, Nunzio Denora, Angela Lopedota, Massimo Franco, Valentino Laquintana
The transport of dopamine across the blood brain barrier represents a challenge for the management of Parkinson's disease. The employment of central nervous system targeted ligands functionalized nanocarriers could be a valid tactic to overcome this obstacle and avoid undesirable side effects. In this work, transferrin functionalized dopamine-loaded liposomes were made by a modified dehydration-rehydration technique from hydrogenated soy phosphatidylcoline, cholesterol and 1,2-stearoyl- sn -glycero-3-phosphoethanolamine- N -[carboxy(poly(ethylene glycol)-2000)]...
March 20, 2018: Nanomaterials
Jin-Xuan Fan, Zi-Hao Li, Xin-Hua Liu, Diwei Zheng, Ying Chen, Xian-Zheng Zhang
Oral drug administration is widely adopted for diverse drugs, and enjoys the convenience of use and capbility to reach different parts of the body via the bloodstream. However, it is generally not feasible for biomacromolecular anti-tumor drugs such as protein and nucleic acids due to the the limited absorption through gastrointestinal tract (GIT) and the poor tumor targeting. Here, we report a non-invasive thermally-sensitive programmable therapetic system using bacteria E. coli MG1655 as an vehicle for tumor treatments via oral administration...
March 20, 2018: Nano Letters
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