Targeted siRNA nanotherapeutics against breast and ovarian metastatic cancer: a comprehensive review of the literature.

Metastasis is considered the major cause of unsuccessful cancer therapy. The metastatic development requires tumor cells to leave their initial site, circulate in the blood stream, acclimate to new cellular environments at a remote secondary site and endure there. There are several steps in metastasis, including invasion, intravasation, circulation, extravasation, premetastatic niche formation, micrometastasis and metastatic colonization.

Effect of Cryo-Processing on Platelet-Rich Autoplasma Preparations.

Unlabelled: Platelet-derived growth factor (PDGF) plays an important role in angiogenesis, affects activation of migration and proliferation of mesenchymal stem cells, fibroblasts, smooth muscle cells, osteoblasts; activation of migration of monocytes, macrophages, and neutrophils. was to study the effect of cryo-processing on the qualitative properties of platelet-rich autoplasma (PRP) at different time intervals.

Materials And Methods: Autologous plasma preparations were obtained from the blood of 31 donors.

Neutrophils as an emerging therapeutic target and tool for cancer therapy.

Activation of neutrophils is necessary for the protection of the host against microbial infection. This property can be used as mode of therapy for cancer treatment. Neutrophils have conflicting dual functions in cancer as either a tumor promoter or inhibitor.

Modification of Nanoparticles with Transferrin for Targeting Brain Tissues.

The delivery of therapeutics to brain tissues is one of the main challenges in neuropathology. For the past two decades, a variety of drug delivery systems has been designed to target components of the blood-brain barrier, including the transferrin receptor, a transmembrane glycoprotein highly expressed in the brain endothelium.In this protocol, we describe the use of transferrin protein to activate the surface of nanoparticles with the aim to direct their uptake in the brain.

Recent Advances in Tumor Targeting via EPR Effect for Cancer Treatment.

Cancer causes the second-highest rate of death world-wide. A major shortcoming inherent in most of anticancer drugs is their lack of tumor selectivity. Nanodrugs for cancer therapy administered intravenously escape renal clearance, are unable to penetrate through tight endothelial junctions of normal blood vessels and remain at a high level in plasma.

Multifunctional polymeric micellar nanomedicine in the diagnosis and treatment of cancer.

Polymeric micelles are a prevalent topic of research for the past decade, especially concerning their fitting ability to deliver drug and diagnostic agents. This delivery system offers outstanding advantages, such as biocompatibility, high loading efficiency, water-solubility, and good stability in biological fluids, to name a few. The multifunctional polymeric micellar architect offers the added capability to adapt its surface to meet the looked-for clinical needs.

Developments in Treatment Methodologies Using Dendrimers for Infectious Diseases.

Dendrimers comprise a specific group of macromolecules, which combine structural properties of both single molecules and long expanded polymers. The three-dimensional form of dendrimers and the extensive possibilities for use of additional substrates for their construction creates a multivalent potential and a wide possibility for medical, diagnostic and environmental purposes. Depending on their composition and structure, dendrimers have been of interest in many fields of science, ranging from chemistry, biotechnology to biochemical applications.

Advances in siRNA delivery strategies for the treatment of MDR cancer.

RNA interference (RNAi) represents a promising therapeutic method that uses siRNA for cancer treatment. Although the RNAi technique has been increasingly used for clinical trials, systemic siRNA delivery into targeted cells is still challenging. The barriers impeding siRNA therapeutics delivery and impacting the treatment outcome must overcome with negligible systemic toxicity for a desirable and successful delivery of siRNA to MDR cancer cells.

Targeted Delivery of Combination Therapeutics Using Monoclonal Antibody 2C5-Modified Immunoliposomes for Cancer Therapy.

Purpose: To develop immunoliposomes modified with monoclonal cancer-specific antibody (mAb) 2C5 and co-loaded with a combination of two chemotherapeutics, in order to simultaneously target bulk cancer cells using paclitaxel and cancer stem cells (CSCs) using salinomycin to prevent cancer growth and metastases.

Methods: Breast cancer cells (MDA-MB-231 and/or SK-BR-3) were chosen as models for all in vitro testing. Liposomes composed of natural phospholipids co-loaded with salinomycin and paclitaxel were prepared and physically characterized.

Monoclonal antibody 2C5 specifically targets neutrophil extracellular traps.

Neutrophils can release DNA and granular cytoplasmic proteins that form smooth filaments of stacked nucleosomes (NS). These structures, called neutrophil extracellular traps (NETs), are involved in multiple pathological processes, and NET formation and removal are clinically significant. The monoclonal antibody 2C5 has strong specificity toward intact NS but not to individual NS components, indicating that 2C5 could potentially target NS in NETs.

Cell penetrating peptides: A versatile vector for co-delivery of drug and genes in cancer.

Biological barriers hamper the efficient delivery of drugs and genes to targeted sites. Cell penetrating peptides (CPP) have the ability to rapidly internalize across biological membranes. CPP have been effective for delivery of various chemotherapeutic agents used to combat cancer.

"Smart" self-assembled structures: toward intelligent dual responsive drug delivery systems.

Combination of various polymeric blocks with distinct characteristics such as thermo-responsiveness, non-ionic nature and zwitterionic properties is an interesting approach toward fabricating copolymers undergoing a smart self-assembly process in an aqueous environment. In some cases, through a so-called "schizophrenic" self-assembly process, stimuli-induced self-assembly can occur from either double-hydrophilic or double hydrophobic polymers. In this process, the roles of the blocks forming the hydrophobic core and hydrophilic shell can be switched by changing the external conditions.

Hypoxia-sensitive micellar nanoparticles for co-delivery of siRNA and chemotherapeutics to overcome multi-drug resistance in tumor cells.

Recently, it has been discovered that the PEG layer on nanoparticle surface can create steric hindrance, preventing efficient cellular uptake of PEGylated nanoparticles. Thus, it would be ideal to have a nanoparticle system that sheds the PEG layer upon reaching the tumor microenvironment. Hypoxia, which is a hallmark of cancerous tumors, can be used as a trigger to shed the PEG layer from the nanoparticle surface.

Charge reversible hyaluronic acid-modified dendrimer-based nanoparticles for siMDR-1 and doxorubicin co-delivery.

Dendrimer-based nanoparticles have shown promising applications in delivery of small interference RNA (siRNA) to downregulate proteins that contribute to multidrug resistance (MDR). Various types of modification can further enhance the anti-tumor efficacy of dendrimer-based nanoparticles. In this study, generation 4 polyamodoamine (PAMAM) was conjugated with PEG-DOPE.

Recent advancements in liposome technology.

The liposomes have continued to be well-recognized as an important nano-sized drug delivery system with attractive properties, such a characteristic bilayer structure assembling the cellular membrane, easy-to-prepare and high bio-compatibility. Extensive effort has been devoted to the development of liposome-based drug delivery systems during the past few decades. Many drug candidates have been encapsulated in liposomes and investigated for reduced toxicity and extended duration of therapeutic effect.

siRNA based drug design, quality, delivery and clinical translation.

Gene silencing by RNA interference represents a promising therapeutic approach. The development of carriers, e.g.

Folate targeted lipid chitosan hybrid nanoparticles for enhanced anti-tumor efficacy.

Folic acid is often used for active targeting of tumor cells to enhance therapeutic outcomes. Here, folic acid was conjugated with chitosan and folate-conjugated chitosan-lipid hybrid nanoparticles were prepared by ionic gelation method using anionic lipid. These nanoparticles were in size range of 200 to 400 nm with spherical shape.

Monoclonal Antibody 2C5-Modified Mixed Dendrimer Micelles for Tumor-Targeted Codelivery of Chemotherapeutics and siRNA.

Targeted delivery of chemotherapeutics to tumors has the potential to reach a high dose at the tumor while minimizing systemic exposure. Incorporation of antibody within a micellar platform represents a drug delivery system for tumor-targeted delivery of antitumor agents. Such modified immunomicelles can result in an increased accumulation of antitumor agents and enhanced cytotoxicity toward cancer cells.

Cytotoxicity of Novel Redox Sensitive PEG-S-S-PTX Micelles against Drug-Resistant Ovarian and Breast Cancer Cells.

Purpose: Since the last decade, it is established that nonspecific delivery of chemotherapeutics fails to effectively treat cancer due to systemic cytotoxicity, poor biodistribution at tumor site and most importantly the development of drug resistance (MDR). Stimuli-sensitive drug delivery systems gained significant attention in recent years for effective tumor therapy and reversal of MDR. The aim of this study was developing a redox sensitive micellar prodrug system, by taking the advantage of the significant difference in GSH levels between extracellular and intracellular environments, but more importantly in healthy and tumor tissues.

A Triple Co-Delivery Liposomal Carrier That Enhances Apoptosis via an Intrinsic Pathway in Melanoma Cells.

The effectiveness of existing anti-cancer therapies is based mainly on the stimulation of apoptosis of cancer cells. Most of the existing therapies are somewhat toxic to normal cells. Therefore, the quest for nontoxic, cancer-specific therapies remains.