Microfluidic preparation and optimization of sorafenib-loaded poly(ethylene glycol-block-caprolactone) nanoparticles for cancer therapy applications.

The use of amphiphilic block copolymers to generate colloidal delivery systems for hydrophobic drugs has been the subject of extensive research, with several formulations reaching the clinical development stages. However, to generate particles of uniform size and morphology, with high encapsulation efficiency, yield and batch-to-batch reproducibility remains a challenge, and various microfluidic technologies have been explored to tackle these issues. Herein, we report the development and optimization of poly(ethylene glycol)-block-(ε-caprolactone) (PEG-b-PCL) nanoparticles for intravenous delivery of a model drug, sorafenib.

Evaluation of the effects of nanoprecipitation process parameters on the size and morphology of poly(ethylene oxide)-block-polycaprolactone nanostructures.

Nanoprecipitation is a straightforward method for the production of block copolymer nanoparticles for drug delivery applications. However, the effects of process parameters need to be understood to optimize and control the particle size distribution (PSD). To this end, we investigated the effects of material and process factors on PSD and morphology of nanoparticles prepared from an amphiphilic diblock copolymer, poly(ethylene oxide)-block-polycaprolactone.

Dual-peptide functionalized acetalated dextran-based nanoparticles for sequential targeting of macrophages during myocardial infarction.

The advent of nanomedicine has recently started to innovate the treatment of cardiovascular diseases, in particular myocardial infarction. Although current approaches are very promising, there is still an urgent need for advanced targeting strategies. In this work, the exploitation of macrophage recruitment is proposed as a novel and synergistic approach to improve the addressability of the infarcted myocardium achieved by current peptide-based heart targeting strategies.

Engineered antibody-functionalized porous silicon nanoparticles for therapeutic targeting of pro-survival pathway in endogenous neuroblasts after stroke.

Generation of new neurons by utilizing the regenerative potential of adult neural stem cells (NSCs) and neuroblasts is an emerging therapeutic strategy to treat various neurodegenerative diseases, including neuronal loss after stroke. Committed to neuronal lineages, neuroblasts are differentiated from NSCs and have a lower proliferation rate. In stroke the proliferation of the neuroblasts in the neurogenic areas is increased, but the limiting factor for regeneration is the poor survival of migrating neuroblasts.

Lipid-polymer hybrid nanoparticles for controlled delivery of hydrophilic and lipophilic doxorubicin for breast cancer therapy.

Lipid polymer hybrid nanoparticles (LPHNPs) for the controlled delivery of hydrophilic doxorubicin hydrochloride (DOX.HCl) and lipophilic DOX base have been fabricated by the single step modified nanoprecipitation method. Poly (D, L-lactide-co-glicolide) (PLGA), lecithin, and 1,2-distearoyl-Sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000 (DSPE-PEG 2000) were selected as structural components.

Cell Membrane-Based Nanoreactor To Mimic the Bio-Compartmentalization Strategy of a Cell.

Organelles of eukaryotic cells are structures made up of membranes, which carry out a majority of functions necessary for the surviving of the cell itself. Organelles also differentiate the prokaryotic and eukaryotic cells, and are arranged to form different compartments guaranteeing the activities for which eukaryotic cells are programmed. Cell membranes, containing organelles, are isolated from cancer cells and erythrocytes and used to form biocompatible and long-circulating ghost nanoparticles delivering payloads or catalyzing enzymatic reactions as nanoreactors.

Development and optimization of methotrexate-loaded lipid-polymer hybrid nanoparticles for controlled drug delivery applications.

Lipid-polymer hybrid nanoparticles (LPHNPs) are emerging platforms for drug delivery applications. In the present study, methotrexate loaded LPHNPs consisted of PLGA and Lipoid S100 were fabricated by employing a single-step modified nanoprecipitation method combined with self-assembly. A three factor, three level Box Behnken design using Design-Expert software was employed to access the influence of three independent variables on the particle size, drug entrapment and percent drug release.

Drug-Loaded Multifunctional Nanoparticles Targeted to the Endocardial Layer of the Injured Heart Modulate Hypertrophic Signaling.

Ischemic heart disease is the leading cause of death globally. Severe myocardial ischemia results in a massive loss of myocytes and acute myocardial infarction, the endocardium being the most vulnerable region. At present, current therapeutic lines only ameliorate modestly the quality of life of these patients.

Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines.

Explosive growth of nanomedicines continues to significantly impact the therapeutic strategies for effective cancer treatment. Despite the significant progress in the development of advanced nanomedicines, successful clinical translation remains challenging. As cancer nanomedicine is a multidisciplinary field, the fundamental problem is that the knowledge gaps stem from different vantage points in the understanding of cancer nanomedicines.

Biomimetic Engineering Using Cancer Cell Membranes for Designing Compartmentalized Nanoreactors with Organelle-Like Functions.

A new biomimetic nanoreactor design is presented based on cancer cell membrane material in combination with porous silicon nanoparticles. This cellular nanoreactor features a biocompartment enclosed by a cell membrane and readily integrated with cells and supplementing the cellular functions under oxidative stress. The study demonstrates the impact of the nanoreactors on improving cellular functions with a potential to serve as artificial organelles.

Quercetin-Based Modified Porous Silicon Nanoparticles for Enhanced Inhibition of Doxorubicin-Resistant Cancer Cells.

One of the most challenging obstacles in nanoparticle's surface modification is to achieve the concept that one ligand can accomplish multiple purposes. Upon such consideration, 3-aminopropoxy-linked quercetin (AmQu), a derivative of a natural flavonoid inspired by the structure of dopamine, is designed and subsequently used to modify the surface of thermally hydrocarbonized porous silicon (PSi) nanoparticles. This nanosystem inherits several advanced properties in a single carrier, including promoted anticancer efficiency, multiple drug resistance (MDR) reversing, stimuli-responsive drug release, drug release monitoring, and enhanced particle-cell interactions.

Active diffusion of nanoparticles of maternal origin within the embryonic brain.

Aim: To investigate porous silicon (PSi) nanoparticles (NPs) behavior in the embryonic brain.

Materials & Methods: Fluorescently labeled PSi NPs were injected into the embryonic brains intraventricularly and to the mother intravenously (iv.).

Angiopep2-functionalized polymersomes for targeted doxorubicin delivery to glioblastoma cells.

A targeted drug delivery nanosystem for glioblastoma multiforme (GBM) based on polymersomes (Ps) made of poly(dimethylsiloxane)-poly(2-methyloxazoline) (PDMS-PMOXA) diblock copolymers was developed to evaluate their potential to actively target brain cancer cells and deliver anticancer drugs. Angiopep2 was conjugated to the surface of preformed Ps to target the low density lipoprotein receptor-related protein 1 that are overexpressed in blood brain barrier (BBB) and glioma cells. The conjugation efficiency yield for angiopep2 was estimated to be 24%.

pH-Switch Nanoprecipitation of Polymeric Nanoparticles for Multimodal Cancer Targeting and Intracellular Triggered Delivery of Doxorubicin.

Theranostic nanoparticles are emerging as potent tools for noninvasive diagnosis, treatment, and monitoring of solid tumors. Herein, an advanced targeted and multistimuli responsive theranostic platform is presented for the intracellular triggered delivery of doxorubicin. The system consists of a polymeric-drug conjugate solid nanoparticle containing encapsulated superparamagnetic iron oxide nanoparticles (IO@PNP) and decorated with a tumor homing peptide, iRGD.

Biocompatible polymer-Peptide hybrid-based DNA nanoparticles for gene delivery.

Currently, research on polymers to be used as gene delivery systems is one of the most important directions in both polymer science and biomedicine. In this report, we describe a five-step procedure to synthesize a novel polymer-peptide hybrid system for gene transfection. The block copolymer based on the biocompatible polymer poly(2-methyl-2-oxazoline) (PMOXA) was combined with the biocleavable peptide block poly(aspartic acid) (PASP) and finally modified with diethylenetriamine (DET).

Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications.

Cancer is a leading cause of death worldwide. Currently available therapies are inadequate and spur demand for improved technologies. Rapid growth in nanotechnology towards the development of nanomedicine products holds great promise to improve therapeutic strategies against cancer.

Advanced Nanomedicines for the Treatment and Diagnosis of Myocardial Infarction and Heart Failure.

Nanotechnology has impacted tremendously the medical research with increasing importance in the development of new therapeutic approaches and applications. Among these applications, the use of nanocarriers has gained particular interest in order to achieve successful delivery of therapeutics and imaging agents for the treatment and diagnostics of different diseases, such as cancer, infections, diabetes, lung, brain and cardiovascular diseases. Heart failure (HF) is a complex clinical syndrome derived from multiple causes that arise from secondary to inherited or acquired abnormalities of cardiac structure and/or function.

Polymersomes conjugated to 83-14 monoclonal antibodies: in vitro targeting of brain capillary endothelial cells.

The blood-brain barrier (BBB) remains an obstacle for many drugs to reach the brain. A strategy to cross the BBB is to modify nanocarrier systems with ligands that bind to endogenous receptors expressed at the BBB to induce receptor-mediated transport. The aim of the present study was to investigate the potential of polymersomes composed of the amphiphilic diblock copolymer poly(dimethylsiloxane)-block-poly(2-methyl-2-oxazoline), PDMS-b-PMOXA, for active targeting of brain capillary endothelial cells.

Polymersomes containing quantum dots for cellular imaging.

Quantum dots (QDs) are highly fluorescent and stable probes for cellular and molecular imaging. However, poor intracellular delivery, stability, and toxicity of QDs in biological compartments hamper their use in cellular imaging. To overcome these limitations, we developed a simple and effective method to load QDs into polymersomes (Ps) made of poly(dimethylsiloxane)-poly(2-methyloxazoline) (PDMS-PMOXA) diblock copolymers without compromising the characteristics of the QDs.

Water-soluble Co(III) complexes of substituted phenanthrolines with cell selective anticancer activity.

Transition metal complexes with substituted phenanthrolines as ligands represent potential anticancer products without the drawbacks of platinum complexes that are currently marketed. Here, we report the synthesis and cell selective anticancer activity of five new water-soluble Co(III) complexes with methyl substituted phenanthroline ligands. The complexes were characterized by elemental analysis, NMR, FAB-mass spectrometry, FTIR, electronic spectroscopy, and single crystal X-ray diffraction.

Aiding nature's organelles: artificial peroxisomes play their role.

A major goal in medical research is to develop artificial organelles that can implant in cells to treat pathological conditions or to support the design of artificial cells. Several attempts have been made to encapsulate or entrap enzymes, proteins, or mimics in polymer compartments, but only few of these nanoreactors were active in cells, and none was proven to mimic a specific natural organelle. Here, we show the necessary steps for the development of an artificial organelle mimicking a natural organelle, the peroxisome.

Light-responsive polymer nanoreactors: a source of reactive oxygen species on demand.

Various domains present the challenges of responding to stimuli in a specific manner, with the desired sensitivity or functionality, and only when required. Stimuli-responsive systems that are appropriately designed can effectively meet these challenges. Here, we introduce nanoreactors that encapsulate photosensitizer-protein conjugates in polymer vesicles as a source of "on demand" reactive oxygen species.

Can polymeric vesicles that confine enzymatic reactions act as simplified organelles?

In various pathological conditions an advantage may be gained by reinforcing an intrinsic organismal response. This can be achieved, for example, by enzyme replacement therapy, which can amplify specific, intrinsic activities of the organelles. In this respect, polymeric nanoreactors composed of vesicles that encapsulate an enzyme or a combination of enzymes in their cavities represent a novel approach in therapeutic applications because they behave like simplified organelles.

Biocompatible functionalization of polymersome surfaces: a new approach to surface immobilization and cell targeting using polymersomes.

Vesicles assembled from amphiphilic block copolymers represent promising nanomaterials for applications that include drug delivery and surface functionalization. One essential requirement to guide such polymersomes to a desired site in vivo is conjugation of active, targeting ligands to the surface of preformed self-assemblies. Such conjugation chemistry must fulfill criteria of efficiency and selectivity, stability of the resulting bond, and biocompatibility.