Nowadays, magnetic hyperthermia constitutes a complementary approach to cancer treatment. The use of magnetic particles as heating mediators, proposed in the 1950s, provides a novel strategy for improving tumor treatment and, consequently, patient quality of life. This review reports a broad overview about several aspects of magnetic hyperthermia addressing new perspectives and the progress on relevant features such as the ad hoc preparation of magnetic nanoparticles, physical modeling of magnetic heating, methods to determine the heat dissipation power of magnetic colloids including the development of experimental apparatus and the influence of biological matrices on the heating efficiency.Comment: 104 pages, 28 figures. Manuscript accepted for publication in Applied Physics Review

Under ordinary circumstances, the membrane tension of a giant unilamellar vesicle is essentially nil. Using visible light, we stretch the vesicles, increasing the membrane tension until the membrane responds by the sudden opening of a large pore (several micrometers in size). Only a single pore is observed at a time in a given vesicle. However, a cascade of transient pores appear, up to 30-40 in succession, in the same vesicle. These pores are transient: they reseal within a few seconds as the inner liquid leaks out. The membrane tension, which is the driving force for pore opening, is relaxed with the opening of a pore and the leakage of the inner liquid; the line tension of the pore's edge is then able to drive the closure of a pore. We use fluorescent membrane probes and real-time videomicroscopy to study the dynamics of the pores. These can be visualized only if the vesicles are prepared in a viscous solution to slow down the leakout of the internal liquid. From measurements of the closure velocity of the pores, we are able to infer the line tension,. We have studied the effect of the shape of inclusion molecules on. Cholesterol, which can be modeled as an inverted cone-shaped molecule, increases the line tension when incorporated into the bilayers. Conversely, addition of cone-shaped detergents reduces. The effect of some detergents can be dramatic, reducing by two orders of magnitude, and increasing pore lifetimes up to several minutes. We give some examples of transport through transient pores and present a rough measurement of the leakout velocity of the inner liquid through a pore. We discuss how our results can be extended to less viscous aqueous solutions which are more relevant for biological systems and biotechnological applications.

We image macroscopic transient pores in mechanically stretched giant vesicles. Holes open above a critical radius r c1 , grow up to a radius r c2 , and close. We interpret the upper limit r c2 by a relaxation of the membrane tension as the holes expand. The closing of the holes is caused by a further relaxation of the surface tension when the internal liquid leaks out. A dynamic model fits our data for the growth and closure of pores.Opening a hole in a biological membrane has been a challenge for drug delivery and gene therapy. Chemical strategies, based on the addition of a suitable agent (1, 2) [detergent proteins such as talin (3)] and physical means (4) [electroporation (5), osmotic shock (6), temperature jump (4), and adhesion on porous (7) or decorated substrates (8) (A. L. Bernard, M. A. GuedeauBoudeville, O.S., S. Palacin, J. M. diMiglio, and L. Jullien, unpublished data), have been developed to increase membrane permeability.Our approach is to stretch the vesicle membrane: even a weak adhesion or an intense light provides a tension , which relaxes by the formation of transient macroscopic pores. The standard difficulty of visualizing directly at video rate the fast dynamics of pore openings and closings is overcome here by the use of a viscous solvent. The role of solvent viscosity is surprising: under tension, vesicles start to burst, very much like viscous bubbles (9), and this is controlled by lipid viscosity. However, as we shall see, there is a leak-out of the internal liquid, which relaxes the tension and induces the closure of the pore. In a solution of low viscosity (like water), leak-out is fast: the pores close before reaching a visible size. If we make the solvent more viscous, leak-out is slowed down: the pores reach sizes up to 10 m. The immersion of vesicles in a viscous environment allows visualization of transient pores in a membrane stretched by either intense illumination or weak adhesion on a solid substrate.For clarity, we begin by presenting in the next section a simple theoretical picture of the pore's dynamics. After that, we describe the experiments.Model of the Opening and Closing of Pores. Closed membranes, such as red blood cells or vesicles, are under zero surface tension in their equilibrium unswollen phase (10). They undulate by thermal fluctuations. The resistance to deformations of the membrane is mainly caused by curvature energy. The surface is crumpled, as shown in Fig. 5a. An excess area ⌬A ϭ A Ϫ A p Ͼ 0 (where A is the total area and A p the projected area) is required to maintain the zero surface-tension state (11-13). When a vesicle adheres to a substrate or is sucked in a glass micropipette, the surface cannot adjust to its optimal value, and a surface tension of is created. The fluctuations of the membrane are strongly reduced, and the shape of the vesicle becomes spherical (Fig. 5b). The micropipette technique allows one to measure the relation between the tension (over four decades, 10 Ϫ3 -10 mN͞m) and the increase of the projected area A p (14). Two r...

When polyelectrolyte-neutral block copolymers are mixed in aqueous solutions with oppositely charged species, stable complexes are found to form spontaneously. The mechanism is based on electrostatics and on the compensation between the opposite charges. Electrostatic complexes exhibit a core-shell microstructure. In the core, the polyelectrolyte blocks and the oppositely charged species are tightly bound and form a dense coacervate microphase. The shell is made of the neutral chains and surrounds the core. In this paper, we report on the structural and magnetic properties of such complexes made from 6.3 nm diameter superparamagnetic nanoparticles (maghemite gamma-Fe(2)O(3)) and cationic-neutral copolymers. The copolymers investigated are poly(trimethylammonium ethylacrylate methyl sulfate)-b-poly(acrylamide), with molecular weights 5000-b-30000 g mol(-)(1) and 110000-b-30000 g mol(-)(1). The mixed copolymer-nanoparticle aggregates were characterized by a combination of light scattering and cryo-transmission electron microscopy. Their hydrodynamic diameters were found in the range 70-150 nm, and their aggregation numbers (number of nanoparticles per aggregate) from tens to hundreds. In addition, Magnetic Resonance Spin-Echo measurements show that the complexes have a better contrast in Magnetic Resonance Imaging than single nanoparticles and that these complexes could be used for biomedical applications.

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. We identified three classes of magnetic responsive composite materials, according to their activation mode and intended applications, which can be defined by the following aspects. (A) Their ability to be deformed (stretching, bending, rotation) upon exposure to a magnetic field. (B) The possibility of remotely dragging them to a targeted area, called magnetic guidance, which is particularly interesting for biomedical applications, including cell and biomolecule guidance and separation. (C) The opportunity to use magnetic induction for thermoresponsive polymer materials actuation, which has shown promising results for controlled drug release and shape memory devices. For each category, essential design parameters that allow fine-tuning of the properties of these magnetic responsive composites are presented using key examples.

International audienceHydrophobically modified maghemite (γ-Fe2O3) 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 a simple access to highly magnetic nanoparticles (MNPs) (loaded up to 70 wt %) together with a good control over the vesicles size (100 to 400 nm). The simultaneous loading of maghemite nanoparticles and doxorubicin was also achieved by nanoprecipitation. The deformation of the vesicle membrane under an applied magnetic field has been evidenced by small angle neutron scattering. These superparamagnetic hybrid self-assemblies display enhanced contrast properties that open potential applications for Magnetic Resonance Imaging. They can also be guided in a magnetic field gradient. The feasibility of controlled drug release by radio-frequency magnetic hyperthermia was demonstrated in the case of encapsulated doxorubicin molecules, showing the viability of the concept of magneto-chemotherapy. These magnetic polymersomes can be used as efficient multifunctional nano-carriers for combined therapy and imaging

We present a detailed analysis of the generation of second-harmonic radiation from biological membranes labeled with a styryl dye. In particular, we consider the high-numerical-aperture limit appropriate to highresolution microscopy in which an excitation beam is tightly focused from the side onto a membrane surface. In this limit the active surface area that contributes to second-harmonic generation (SHG) depends only on the tightness of the beam focus and the SHG radiation is confined by phase matching into two well-defined off-axis lobes. We derive expressions for the SHG radiation power, angular distribution, and polarization dependence in the cases of ideal or nonideal molecular alignment in the membrane and uniaxiality of the molecular hyperpolarizability. We define an SHG cross section similar to that used in two-photon-excited fluorescence (TPEF) to permit direct comparison of the two imaging modalities. Finally, we corroborate our results with experiments based on the excitation of a styryl dye in giant unilamellar vesicles with a mode-locked Ti:sapphire laser.

Magnetic particles are very efficient magnetic resonance imaging (MRI) contrast agents. In recent years, chemists have unleashed their imagination to design multi-functional nanoprobes for biomedical applications including MRI contrast enhancement. This study is focused on the direct relationship between the size and magnetization of the particles and their nuclear magnetic resonance relaxation properties, which condition their efficiency. Experimental relaxation results with maghemite particles exhibiting a wide range of sizes and magnetizations are compared to previously published data and to well-established relaxation theories with a good agreement. This allows deriving the experimental master curve of the transverse relaxivity versus particle size and to predict the MRI contrast efficiency of any type of magnetic nanoparticles. This prediction only requires the knowledge of the size of the particles impermeable to water protons and the saturation magnetization of the corresponding volume. To predict the T(2) relaxation efficiency of magnetic single crystals, the crystal size and magnetization - obtained through a single Langevin fit of a magnetization curve - is the only information needed. For contrast agents made of several magnetic cores assembled into various geometries (dilute fractal aggregates, dense spherical clusters, core-shell micelles, hollow vesicles…), one needs to know a third parameter, namely the intra-aggregate volume fraction occupied by the magnetic materials relatively to the whole (hydrodynamic) sphere. Finally a calculation of the maximum achievable relaxation effect - and the size needed to reach this maximum - is performed for different cases: maghemite single crystals and dense clusters, core-shell particles (oxide layer around a metallic core) and zinc-manganese ferrite crystals.