Simultaneous Drug and Gene Delivery from the Biodegradable Poly(ε-caprolactone) Nanofibers for the Treatment of Liver Cancer

2015 ◽  
Vol 15 (10) ◽  
pp. 7971-7975 ◽  
Author(s):  
Hui-Lian Che ◽  
Hwa Jeong Lee ◽  
Koichiro Uto ◽  
Mitsuhiro Ebara ◽  
Won Jong Kim ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Liver Cancer ◽  
Sustained Release ◽  
Liver Tumors ◽  
Cancer Drug ◽  
Therapeutic Gene ◽  
Anti Cancer ◽  
Drug And Gene Delivery

In this study, we present anti-cancer drug containing nanofiber-mediated gene delivery to treat liver cancer. Electro-spun nanofibers have big potential for local delivery and sustained release of therapeutic gene and drugs. We reported a temperature-responsive nanofibers mainly compounded by branched poly(ε-caprolactone) (PCL) macro-monomers and anti-cancer drug paclitaxel. The nanofiber could be administrated into liver tumors to dramatically hinder their growth and prevent their metastasis. As a result, paclitaxel encapsulated PCL (PTX/PCL) nanofibers with diameters of around several tens nanometers to 10 nm were successfully obtained by electro-spinning andobserved in scanning electron microscopy (SEM). Nanoparticles composed of disulfide cross-linked branched PEI (ssPEI) and anti-cancer therapeutic gene miRNA-145 were complexed based on the electrostatic interaction and coated over the paclitaxel-loaded nanofiber. MicroRNA 145/ssPEI nanoparticles (MSNs) immobilized on the PTX/PCL nanofiber showed time-dependent sustained release of the microRNA for enhanced uptake in neighboring liver cancer cells without any noticeable cytotoxicity. From this study we are expecting a synergistic effect on the cancer cell suppression since we have combined the drug and gene delivery. This approach uses the nanofibers and nanoparticles together for the treatment of cancer and the detailed investigation in vitro and in vivo must be conducted for the practicality of this study. The polymer is biodegradable and the toxicity issues must be cleared by our approach.

Prevascularized, Co-Culture Model for Breast Cancer Drug Development

2012 ◽  
Author(s):  
Lauren Marshall ◽  
Isabel Löwstedt ◽  
Paul Gatenholm ◽  
Joel Berry
Keyword(s):  
Breast Cancer ◽  
Drug Development ◽  
Three Dimensional ◽  
Human Tumor ◽  
3D Models ◽  
Cancer Drug ◽  
Cancer Therapies ◽  
Anti Cancer

The objective of this study was to create 3D engineered tissue models to accelerate identification of safe and efficacious breast cancer drug therapies. It is expected that this platform will dramatically reduce the time and costs associated with development and regulatory approval of anti-cancer therapies, currently a multi-billion dollar endeavor [1]. Existing two-dimensional (2D) in vitro and in vivo animal studies required for identification of effective cancer therapies account for much of the high costs of anti-cancer medications and health insurance premiums borne by patients, many of whom cannot afford it. An emerging paradigm in pharmaceutical drug development is the use of three-dimensional (3D) cell/biomaterial models that will accurately screen novel therapeutic compounds, repurpose existing compounds and terminate ineffective ones. In particular, identification of effective chemotherapies for breast cancer are anticipated to occur more quickly in 3D in vitro models than 2D in vitro environments and in vivo animal models, neither of which accurately mimic natural human tumor environments [2]. Moreover, these 3D models can be multi-cellular and designed with extracellular matrix (ECM) function and mechanical properties similar to that of natural in vivo cancer environments [3].

Inorganic Nanoparticles and Nanomaterials Based on Titanium (Ti): Applications in Medicine

2013 ◽  
Vol 754 ◽  
pp. 21-87 ◽  
Author(s):  
Zeid A. Al Othman ◽  
Mohammad Mezbaul Alam ◽  
Mu. Naushad ◽  
Inamuddin ◽  
Mohd Farhan Khan
Keyword(s):  
Drug Delivery ◽  
Gene Delivery ◽  
Cell Tracking ◽  
Conventional Medicine ◽  
Inorganic Nanoparticles ◽  
Cell Labeling ◽  
Body Parts ◽  
Drug And Gene Delivery

Nanomedicine is a relatively new field of science and technology. By interacting with biomolecules, therefore at nanoscale, nanotechnology opens up a vast field of research and application. Current and potential applications of nanotechnology in medicine range from research involving diagnostic devices, drug delivery vehicles to enhanced gene therapy and tissue engineering procedures. Its advantage over conventional medicine lies on its size. Operating at nanoscale allows to exploit physical properties different from those observed at microscale such as the volume/surface ratio. This allows drugs of nanosize be used in lower concentration and has an earlier onset of therapeutic action. It also provides materials for controlled drug delivery by directing carriers to a specific location. Inorganic nanomedicine is likely to remain one of the most prolific fields of nanomedicine, which refers to the use of inorganic or hybrid (inorganic-inorganic or inorganic-organic) nanomaterials (INMs) and nanoparticles (INPs) to achieve innovative medical advances for body parts implantation, drug and gene discovery and delivery, discovery of biomarkers, and molecular diagnostics. Among the most promising INMs being developed are metal, silica, dendrimers, organic-inorganic hybrids, ceramics (e.g. ZrO2, TiO2, Al2O3, etc.) and bioinorganic hybrids. Metal NP contrast agents enhance magnetic resonance imaging and ultrasound results in biomedical applications of in vivo imaging. Hollow and porous INMs have been exploited for drug and gene delivery, diagnostic imaging, and photothermal therapy. Biomolecular inorganic nanohybrids and nanostructured biomaterials have been exploited for targeted imaging and therapy, drug and gene delivery, and regenerative medicine. Potential uses for fluorescent quantum dots (QDs) include cell labeling, biosensing, in vivo imaging, bimodal magnetic-luminescent imaging, and diagnostics. Biocompatible QD conjugates have been used successfully for sentinel lymph node mapping, tumor targeting, tumor angiogenesis imaging, and metastasis cell tracking. This article outlines present developments and future prospects for the use of Ti-based NPs and NMs in experimental in vivo and in vitro studies and in engineering nanodevices and biosensors for clinical and investigative use in diagnosis and therapy in diverse fields of medical sciences, such as oncology, infection control, orthopedics, dentistry, dermatology, genetics, cardiology, ophthalmology, etc. Toxicological considerations of these INPs and INMs are also discussed.

scholarly journals Frontiers in Anti-cancer Drug Discovery: Challenges and Perspectives of Metformin as Anti-angiogenic Add-on Therapy in Glioblastoma

2021 ◽  
Author(s):  
Laura Guarnaccia ◽  
Stefania Elena Navone ◽  
Matteo Maria Masseroli ◽  
Melissa Balsamo ◽  
Manuela Caroli ◽  
...  
Keyword(s):  
Target Therapy ◽  
Cancer Drug ◽  
Cancer Drug Discovery ◽  
Average Survival ◽  
Anti Cancer ◽  
Tumor Neovascularization ◽  
Novel Therapeutic Strategies

Glioblastoma (GBM) is the most common primitive tumor in adult central nervous system (CNS), classified as grade IV according to WHO 2016 classification. GBM shows a poor prognosis with an average survival of approximately 15 months, representing an extreme therapeutic challenge. One of its distinctive and aggressive features is aberrant angiogenesis, which drives tumor neovascularization, representing a promising candidate for molecular target therapy. Although several pre-clinical studies and clinical trials have shown promising results, anti-angiogenic drugs have not led to a significant improvement in overall survival (OS), suggesting the necessity of identifying novel therapeutic strategies. Metformin, an anti-hyperglycemic drug of the Biguanides family, used as first line treatment in Type 2 Diabetes Mellitus (T2DM), demonstrated in vitro and in vivo antitumoral efficacy in many different tumors, including GBM. From this evidence, a process of repurposing of the drug has begun, leading to the demonstration of the inhibition of various oncopromoter mechanisms and, consequently, to the identification of the molecular pathways involved. Here, we review and discuss the potential metformin’s antitumoral effects on GBM, inspecting if it could properly act as an anti-angiogenic compound to be considered as a safely add-on therapy in the treatment and management of GBM patients.

scholarly journals Coherent Raman Scattering Microscopy in Oncology Pharmacokinetic Research

2021 ◽  
Vol 12 ◽  
Author(s):  
Junjie Zeng ◽  
Wenying Zhao ◽  
Shuhua Yue
Keyword(s):  
Raman Scattering ◽  
High Speed ◽  
Cancer Drug ◽  
Cancer Drugs ◽  
High Speed Imaging ◽  
Coherent Raman Scattering ◽  
Anti Cancer ◽  
Coherent Raman

The high attrition rates of anti-cancer drugs during clinical development remains a bottleneck problem in pharmaceutical industry. This is partially due to the lack of quantitative, selective, and rapid readouts of anti-cancer drug activity in situ with high resolution. Although fluorescence microscopy has been commonly used in oncology pharmacological research, fluorescent labels are often too large in size for small drug molecules, and thus may disturb the function or metabolism of these molecules. Such challenge can be overcome by coherent Raman scattering microscopy, which is capable of chemically selective, highly sensitive, high spatial resolution, and high-speed imaging, without the need of any labeling. Coherent Raman scattering microscopy has tremendously improved the understanding of pharmaceutical materials in the solid state, pharmacokinetics of anti-cancer drugs and nanocarriers in vitro and in vivo. This review focuses on the latest applications of coherent Raman scattering microscopy as a new emerging platform to facilitate oncology pharmacokinetic research.

scholarly journals Polymeric micelles from poly(ethylene glycol)–poly(amino acid) block copolymer for drug and gene delivery

2009 ◽  
Vol 6 (suppl_3) ◽  
Author(s):  
Kensuke Osada ◽  
R. James Christie ◽  
Kazunori Kataoka
Keyword(s):  
Gene Delivery ◽  
Polymeric Micelles ◽  
Genetic Diseases ◽  
Cancer Drug ◽  
Biological Research ◽  
Medical Treatments ◽  
Technical Problems ◽  
Anti Cancer ◽  
Poly Ethylene ◽  
Drug And Gene Delivery

Dramatic advances in biological research have revealed the mechanisms underlying many diseases at the molecular level. However, conventional techniques may be inadequate for direct application of this new knowledge to medical treatments. Nanobiotechnology, which integrates biology with the rapidly growing field of nanotechnology, has great potential to overcome many technical problems and lead to the development of effective therapies. The use of nanobiotechnology in drug delivery systems (DDS) is attractive for advanced treatment of conditions such as cancer and genetic diseases. In this review paper for a special issue on biomaterial research in Japan, we discuss the development of DDS based on polymeric micelles mainly in our group for anti-cancer drug and gene delivery, and also address our challenges associated with developing polymeric micelles as super-functionalized nanodevices with intelligent performance.

scholarly journals Histone demethylase JMJD2D promotes the self-renewal of liver cancer stem-like cells by enhancing EpCAM and Sox9 expression

2020 ◽  
pp. jbc.RA120.015335
Author(s):  
Yuan Deng ◽  
Ming Li ◽  
Minghui Zhuo ◽  
Peng Guo ◽  
Qiang Chen ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Cancer Progression ◽  
Liver Tumors ◽  
The Self ◽  
High Rate ◽  
Sox9 Expression ◽  
Self Renewal ◽  
Lysine Demethylase

Cancer stem-like cells (CSCs) contribute to the high rate of tumor heterogeneity, metastasis, therapeutic resistance, and recurrence. Histone lysine demethylase 4D (KDM4D or JMJD2D) is highly expressed in colon and liver tumors, where it promotes cancer progression; however, the role of JMJD2D in CSCs remains unclear. Here, we show that JMJD2D expression was increased in liver cancer stem-like cells (LCSCs); downregulation of JMJD2D inhibited the self-renewal of LCSCs in vitro and in vivo and inhibited the lung metastasis of LCSCs by reducing the survival and the early lung seeding of circulating LCSCs. Mechanistically, JMJD2D promoted LCSC self-renewal by enhancing the expression of CSC markers EpCAM and Sox9; JMJD2D reduced H3K9me3 levels on the promoters of EpCAM and Sox9 to enhance their transcription via interaction with β-catenin/TCF4 and Notch1 intracellular domain, respectively. Restoration of EpCAM and Sox9 expression in JMJD2D-knockdown liver cancer cells rescued the self-renewal of LCSCs. Pharmacological inhibition of JMJD2D using 5-c-8HQ reduced the self-renewal of LCSCs and liver cancer progression. Collectively, our findings suggest that JMJD2D promotes LCSC self-renewal by enhancing EpCAM and Sox9 expression via Wnt/β-catenin and Notch signaling pathways and is a potential therapeutic target for liver cancer.

scholarly journals New Anti-Cancer Strategy to Suppress Colorectal Cancer Growth Through Inhibition of ATG4B and Lysosome Function

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1523 ◽  
Author(s):  
Yuanyuan Fu ◽  
Qianqian Gu ◽  
Li Luo ◽  
Jiecheng Xu ◽  
Yuping Luo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Therapy ◽  
Therapeutic Strategy ◽  
Screening Method ◽  
Cancer Drug ◽  
Autophagic Flux ◽  
Single Target ◽  
Anti Cancer

Autophagy inhibition has been proposed to be a potential therapeutic strategy for cancer, however, few autophagy inhibitors have been developed. Recent studies have indicated that lysosome and autophagy related 4B cysteine peptidase (ATG4B) are two promising targets in autophagy for cancer therapy. Although some inhibitors of either lysosome or ATG4B were reported, there are limitations in the use of these single target compounds. Considering multi-functional drugs have advantages, such as high efficacy and low toxicity, we first screened and validated a batch of compounds designed and synthesized in our laboratory by combining the screening method of ATG4B inhibitors and the identification method of lysosome inhibitors. ATG4B activity was effectively inhibited in vitro. Moreover, 163N inhibited autophagic flux and caused the accumulation of autolysosomes. Further studies demonstrated that 163N could not affect the autophagosome-lysosome fusion but could cause lysosome dysfunction. In addition, 163N diminished tumor cell viability and impaired the development of colorectal cancer in vivo. The current study findings indicate that the dual effect inhibitor 163N offers an attractive new anti-cancer drug and compounds having a combination of lysosome inhibition and ATG4B inhibition are a promising therapeutic strategy for colorectal cancer therapy.

scholarly journals Targeted Protein Liposomes-Mediated AChE Gene Therapy for Effective Liver Cancer Treatment

2020 ◽  
Author(s):  
Kai Wang ◽  
Fusheng Shang ◽  
Dagui Chen ◽  
Jianpeng Jiao ◽  
Tieliu Cao ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Liver Cancer ◽  
Nude Mice ◽  
Transfection Efficiency ◽  
Tumor Therapy ◽  
Viral Gene ◽  
Therapeutic Gene ◽  
Vector Systems

Abstract The development of highly efficient non-viral gene vector systems has very important application value in the field of cancer therapy. The high protein content of proteolipids allows for high biocompatibility, low immunogenicity, and surface modification of proteins to confer more targeted drug/gene function. For the first time, this study selected transferrin, which has hepatocellular carcinoma cell targeting function, with a liposome backbone material to construct transferrin liposome (Tf-PL), and load acetylcholinesterase (AChE) therapeutic gene for in vitro and in vivo functions evaluation. The results showed that the Tf-PL transfection efficiency was higher than that of commercial Lipo 2000, low cytotoxicity and targeted ability to liver cancer SMMC-7721 cells. After tail vein injection, Tf-PL/AChE can effectively target to liver cancer, significantly inhibiting the growth of liver cancer xenografts in nude mice, prolonging the survival time of tumor-bearing nude mice, and also does not cause significant systemic toxicities. Our study provides a strategy for proteolipids targeting the transferrin receptor to carry therapeutic gene therapy for tumors. This method has strong tumor affinity and can provide an effective vector selection for precise tumor therapy.

scholarly journals Validation of a novel perfusion bioreactor system in cancer research

2020 ◽  
Vol 74 (3) ◽  
pp. 187-196
Author(s):  
Jasmina Stojkovska ◽  
Jovana Zvicer ◽  
Milena Milivojevic ◽  
Isidora Petrovic ◽  
Milena Stevanovic ◽  
...  
Keyword(s):  
Cancer Research ◽  
Drug Screening ◽  
Cancer Drug ◽  
Perfusion Bioreactor ◽  
Animal Testing ◽  
Anti Cancer ◽  
Medium Flow ◽  
Bioreactor System

Development of drugs is a complex, time- and cost-consuming process due to the lack of standardized and reliable characterization techniques and models. Traditionally, drug screening is based on in vitro analysis using two-dimensional (2D) cell cultures followed by in vivo animal testing. Unfortunately, application of the obtained results to humans in about 90 % of cases fails. Therefore, it is important to develop and improve cell-based systems that can mimic the in vivo-like conditions to provide more reliable results. In this paper, we present development and validation of a novel, user-friendly perfusion bioreactor system for single use aimed for cancer research, drug screening, anti-cancer drug response studies, biomaterial characterization, and tissue engineering. Simple design of the perfusion bioreactor provides direct medium flow at physiological velocities (100?250 ?m s-1) through samples of different sizes and shapes. Biocompatibility of the bioreactor was confirmed in short term cultivation studies of cervical carcinoma SiHa cells immobilized in alginate microfibers under continuous medium flow. The results have shown preserved cell viability indicating that the perfusion bioreactor in conjunction with alginate hydrogels as cell carriers could be potentially used as a tool for controlled anti-cancer drug screening in a 3D environment.

scholarly journals Scaffold-Mediated Gene Delivery for Osteochondral Repair

Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 930 ◽  
Author(s):  
Henning Madry ◽  
Jagadeesh Kumar Venkatesan ◽  
Natalia Carballo-Pedrares ◽  
Ana Rey-Rico ◽  
Magali Cucchiarini
Keyword(s):  
Gene Delivery ◽  
Viral Vectors ◽  
Viral Gene ◽  
Therapeutic Gene ◽  
Therapeutic Concept ◽  
Osteochondral Repair ◽  
Gene Vectors ◽  
A Site

Osteochondral defects involve both the articular cartilage and the underlying subchondral bone. If left untreated, they may lead to osteoarthritis. Advanced biomaterial-guided delivery of gene vectors has recently emerged as an attractive therapeutic concept for osteochondral repair. The goal of this review is to provide an overview of the variety of biomaterials employed as nonviral or viral gene carriers for osteochondral repair approaches both in vitro and in vivo, including hydrogels, solid scaffolds, and hybrid materials. The data show that a site-specific delivery of therapeutic gene vectors in the context of acellular or cellular strategies allows for a spatial and temporal control of osteochondral neotissue composition in vitro. In vivo, implantation of acellular hydrogels loaded with nonviral or viral vectors has been reported to significantly improve osteochondral repair in translational defect models. These advances support the concept of scaffold-mediated gene delivery for osteochondral repair.

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