Single-molecule mechanical unfolding experiments reveal a critical length for the formation of α-helices in peptides.

α-Helix is the most predominant secondary structure in proteins and supports many functions in biological machineries. The conformation of the helix is dictated by many factors such as its primary sequence, intramolecular interactions, or the effect of the close environment. Several computational studies have proposed that there is a critical maximum length for the formation of intact compact helical structures, supporting the fact that most intact α-helices in proteins are constituted of a small number of amino acids.

Cellular Uptake and Cytotoxic Effect of Epidermal Growth Factor Receptor Targeted and Plitidepsin Loaded Co-Polymeric Polymersomes on Colorectal Cancer Cell Lines.

Encapsulating chemotherapy drugs in targeted nanodelivery systems is one of the most promising approaches to tackle cancer disease, avoiding side effects of common treatment. In the last decade, several nanocarriers with different nature have been tested, but polypeptide-based copolymers have attracted considerable attention for their biocompatibility, controlled and slow biodegradability as well as their low toxicity. In this work, we synthesized, characterized and evaluated poly(trimethylene carbonate)-bock-poly(L-glutamic acid) derived polymersomes, targeted to epidermal growth factor receptor (EGFR), loaded with plitidepsin and ultimately tested in HT29 and LS174T colorectal cancer cell lines for specificity and efficacy.

Nano-thermometers with thermo-sensitive polymer grafted USPIOs behaving as positive contrast agents in low-field MRI.

Two commercial statistical copolymers of ethylene oxide and propylene oxide, Jeffamine® M-2005 (PEO5-st-PPO37) and M-2070 (PEO46-st-PPO13), exhibiting lower critical solution temperature (LCST) in water, were grafted onto the surface of ultra-small superparamagnetic iron oxide nanoparticles (USPIOs) using silanization and amide-bond coupling reactions. The LCSTs of the polymers in solution were measured by dynamic light scattering (DLS) and nuclear magnetic resonance (NMR). In accordance with the compositions of EO vs.

Amphiphilic PEO-b-PBLG diblock and PBLG-b-PEO-b-PBLG triblock copolymer based nanoparticles: doxorubicin loading and in vitro evaluation.

Huisgen's 1,3-dipolar cycloaddition ("Click Chemestry") has been used to prepare amphiphilic PEO-b-PBLG diblock and PBLG-b-PEO-b-PBLG triblock copolymers as potential carriers of anticancer drugs. Spherical and flower shaped micelles (D ≈ 100 nm) were obtained from diblock and triblock copolymers respectively. DOX was effectively encapsulated up to 18 wt.

Nano-encapsulation of plitidepsin: in vivo pharmacokinetics, biodistribution, and efficacy in a renal xenograft tumor model.

Purpose: Plitidepsin is an antineoplasic currently in clinical evaluation in a phase III trial in multiple myeloma (ADMYRE). Presently, the hydrophobic drug plitidepsin is formulated using Cremophor®, an adjuvant associated with unwanted hypersensitivity reactions. In search of alternatives, we developed and tested two nanoparticle-based formulations of plitidepsin, aiming to modify/improve drug biodistribution and efficacy.

Hybrid iron oxide-copolymer micelles and vesicles as contrast agents for MRI: impact of the nanostructure on the relaxometric properties.

Magnetic resonance imaging (MRI) is at the forefront of non-invasive medical imaging techniques. It provides good spatial and temporal resolution that can be further improved by the use of contrast agents (CAs), providing a valuable tool for diagnostic purposes. Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are attractive MRI contrast agents due to their negative (T) contrast enhancement capability and biocompatibility.

Magnetic responsive polymer composite materials.

Magnetic responsive materials are the topic of intense research due to their potential breakthrough applications in the biomedical, coatings, microfluidics and microelectronics fields. By merging magnetic and polymer materials one can obtain composites with exceptional magnetic responsive features. Magnetic actuation provides unique capabilities as it can be spatially and temporally controlled, and can additionally be operated externally to the system, providing a non-invasive approach to remote control.

Antibody-functionalized magnetic polymersomes: in vivo targeting and imaging of bone metastases using high resolution MRI.

Multifunctional polymersomes loaded with maghemite nanoparticles and grafted with an antibody, directed against human endothelial receptor 2, are developed as novel MRI contrast agents for bone metastasis imaging. Upon administration in mice bearing bone tumor grown from human breast cancer cells, MR images show targeting and enhanced retention of antibody-labeled polymersomes at the tumor site.

Polymeric micelles and vesicles: biological behavior evaluation using radiolabeling techniques.

The application of combined diagnosis and therapy through nanotechnology applications is attracting increasing attention worldwide. Polymeric self-assembled nanoparticles (NPs) have been studied for this purpose. Micelles and vesicles with or without a magnetic core can efficiently carry diagnostic and/or therapeutic agents to a desired target.

Magnetic field triggered drug release from polymersomes for cancer therapeutics.

Local and temporal control of drug release has for long been a main focus in the development of novel drug carriers. Polymersomes, which can load both hydrophilic and hydrophobic species and, at the same time, be tailored to respond to a desired stimulus, have drawn much attention over the last decade. Here we describe polymersomes able to encapsulate up to 6% (w/w) of doxorubicin (DOX) together with 30% (w/w) of superparamagnetic iron oxide nanoparticles (USPIO; γ-Fe2O3).

Smart polymersomes for therapy and diagnosis: fast progress toward multifunctional biomimetic nanomedicines.

Rising from the shortcomings of modern day therapeutics there is a need for a controlled approach in carrier-mediated drug delivery. Polymeric vesicles, also called polymersomes, are powerful tools to address issues of efficacy, specificity, and controlled release of drugs to diseased tissues. These recent, biomimetic structures are able to overcome the body's natural defences, remaining stable for extended time in circulation, have tuneable membrane properties, allowing the control of membrane permeability and therefore of drug release, and have the potential to be functionalized for active targeting of specific tissues, reducing undesirable side effects.

Biologically active polymersomes from amphiphilic glycopeptides.

Polypeptide block copolymers with different block length ratios were obtained by sequential ring-opening polymerization of benzyl-L-glutamate and propargylglycine (PG) N-carboxyanhydrides. Glycosylation of the poly(PG) block was obtained by Huisgens cycloaddition "click" reaction using azide-functionalized galactose. All copolymers were self-assembled using the nanoprecipitation method to obtain spherical and wormlike micelles as well as polymersomes depending on the block length ratio and the nanoprecipitation conditions.

Doxorubicin loaded magnetic polymersomes: theranostic nanocarriers for MR imaging and magneto-chemotherapy.

Hydrophobically modified maghemite (γ-Fe(2)O(3)) nanoparticles were encapsulated within the membrane of poly(trimethylene carbonate)-b-poly(l-glutamic acid) (PTMC-b-PGA) block copolymer vesicles using a nanoprecipitation process. This formation method gives simple access to highly magnetic nanoparticles (MNPs) (loaded up to 70 wt %) together with good control over the vesicles size (100-400 nm). The simultaneous loading of maghemite nanoparticles and doxorubicin was also achieved by nanoprecipitation.

A simple method to achieve high doxorubicin loading in biodegradable polymersomes.

Doxorubicin (Dox), an anthracycline anticancer drug, was successfully incorporated into block copolymer vesicles of poly(trimethylene carbonate)-b-poly(L-glutamic acid) (PTMC-b-PGA) by a solvent-displacement (nanoprecipitation) method. pH conditions were shown to have a strong influence on loading capacity and release profiles. Substantial drug loading (47% w/w) was achieved at pH 10.

Effect of the polymer nature on the structural organization of lipid/polymer particle assemblies.

The nano-organized LipoParticle assemblies, consisting of polymer particles coated with lipid layers, are investigated with the aim of evidencing the impact of the particle chemical nature on their physicochemical behavior. To this end, these colloidal systems are elaborated from anionic submicrometer poly(styrene) (P(St)) or poly(lactic acid) (PLA) particles, and lipid mixtures composed of zwitterionic 1,2-dipalmitoyl- sn-glycero-3-phosphocholine (DPPC) and cationic 1,2-dipalmitoyl-3-trimethylammonium-propane (DPTAP). As revealed by various experimental techniques, such as quasielastic light scattering, zeta potential measurements, transmission electron microscopy, and 1H NMR spectroscopy, the features of both LipoParticle systems are similar when cationic lipid formulations (DPPC/DPTAP mixtures) are used.

Steric stabilization of lipid/polymer particle assemblies by poly(ethylene glycol)-lipids.

Biocompatible and biodegradable assemblies consisting of spherical particles coated with lipid layers were prepared from sub-micrometer poly(lactic acid) particles and lipid mixtures composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-dipalmitoyl-3-trimethylammonium-propane. These original colloidal assemblies, named LipoParticles, are of a great interest in biotechnology and biomedicine. Nevertheless, a major limitation of their use is their poor colloidal stability toward ionic strength.