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Abstract Nucleic acids (NAs) have been considered as promising therapeutic agents for various types of diseases. However, their clinical applications still face many limitations due to their charge, high molecular weight, instability in biological environment and low levels of transfection. To overcome these drawbacks, therapeutic NAs should be carried in a stable nanocarrier, which can be viral or non-viral vectors, and released at specific target site. Various controllable gene release strategies are currently being evaluated with interesting results. Endogenous stimuli-responsive systems, for example pH-, redox reaction-, enzymatic-triggered approaches have been widely studied based on the physiological differences between pathological and normal tissues. Meanwhile, exogenous triggered release strategies require the use of externally non-invasive physical triggering signals such as light, heat, magnetic field and ultrasound. Compared to internal triggered strategies, external triggered gene release is time and site specifically controllable through active management of outside stimuli. The signal induces changes in the stability of the delivery system or some specific reactions which lead to endosomal escape and/or gene release. In the present review, the mechanisms and examples of exogenous triggered gene release approaches are detailed. Challenges and perspectives of such gene delivery systems are also discussed. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

Cationic liposomes have been considered as potential vectors for gene delivery thanks to their ability to transfect cells with high efficiency. Recently, the combination of diagnostic agent and therapeutic agents in the same particle to form a theranostic system has been reported. Magnetic liposomes are one of these examples. Due to the magnetic nanoparticles encapsulated in the liposomes, they can act as a drug delivery system and, at the same time, a magnetic resonance imaging contrast enhancement agent or hyperthermia. In this work, nucleic acid delivery systems based on magnetic cationic liposomes (MCLs) were developed. Two different techniques, reverse phase evaporation and cosolvent sonication, were employed for liposome preparation. Both strategies produced MCLs of less than 200 nm with highly positive charge. Enhancement of their transverse and longitudinal relaxivities r2 and r1 was obtained with both kinds of magnetic liposomes compared to free magnetic nanoparticles. Moreover, these MCLs showed high capacity to form complexes and transfect CT-26 cells using the antibiotic-free pFAR4-luc plasmid. The transfection enhancement with magnetofection was also carried out in CT26 cells. These results suggested that our MCLs could be a promising candidate for image-guided gene therapy. [ABSTRACT FROM AUTHOR]

The combination of magnetic fluid hyperthermia and magnetic resonance imaging is recently considered to be one of the most promising non-invasive cancer treatment. In this work, a highly stable ferrofluid based on magnetite nanoparticles with high magnetization and high specific absorption rate will be developed. The ferrofluid was synthesized by thermal decomposition using poly (maleic anhydride-alt-1-octadecene, noted as PMAO) as a phase transferring ligand. The results have demonstrated that the magnetic particles were fully covered at high coverage by long non-magnetic polymeric chains. The particle size was increased by 25–30% while the saturation magnetization was decreased approximately 7–9% after phase transfer process. Remarkably, the prepared ferrofluid revealed excellent colloidal stability over six months of storage with zeta potentials less than −40 mV. As consequently, a relatively high specific absorption rate of 66 W.g-1 was obtained at ferrofluid concentration of only 5 mg.mL-1. Additionally, high-resolution magnetic resonance images with improved transverse relaxation T2 were observed when using magnetite-based ferrofluid for both in-vitro and in-vivo tests. This study demonstrates a novel approach for tailoring magnetic nanoparticles applicable in magnetic fluid hyperthermia and imaging of tumor cells. Image 1 • Fe3O4 magnetic nanoparticles were synthesized by thermal decomposition method. • Fe3O4@PMAO ferrofluids revealed excellent colloidal stability over 6 storage months. • The SAR of 66.04 W.g-1 was obtained at ferrofluid concentration of only 5 mg.mL-1. • T2-weighted intensity in ferrofluid-injected tissues was increased by 5.85 times. [ABSTRACT FROM AUTHOR]

In this study, a multifunctional drug delivery nanosystem Fe3O4–CdTe–alginate (FAQ) was prepared by coating Fe3O4 nanoparticles and CdTe quantum dots (QDs) simultaneously with alginate. High luminescent CdTe QDs can help label the cells for diagnostics while the superparamagnetic Fe3O4 component endows the abilities of hyperthermia and magnetic targeting to the system for cancer treatment. Besides, polymeric alginate provides biocompatibility and high stability (Zeta potential of −49.1 mV) and makes it possible to encapsulate cancer drug Doxorubicin (Dox) in the system. The fluorescence spectra of blank FAQ and FAQ loading Dox (FAQD) were analysed and compared to those of pure CdTe or Dox to confirm the formation of the nanosystems. Next, the samples were applied to in vitro treatment with several human cell lines (Hep-G2, LU-1, RD and Vero cell lines) and showed positive results with low IC50 values for these cells and exhibited higher impact of apoptosis induction and MCF7 spheroid growth delay compared to pure Dox. In particular, FAQ and FAQD have high values of r2 and show contrast increment in the MRI images. The results indicate that FAQ and FAQD can serve as excellent candidates for both cancer therapy and diagnostics. [ABSTRACT FROM AUTHOR]

Since its discovery, evidence that siRNA was able to act as an RNA interference effector, led to its acceptation as a novel medicine. The siRNA approach is very effective, due to its catalytic mechanism, but still the limitations of its cellular delivery should be addressed. One promising form of non-viral gene delivery system is liposomes. The variable and versatile nature of the lipids keeps the possibility to upgrade the liposomal structure, which makes them suitable for encapsulation and delivery of drugs. However, to avoid the limitation of fast release for the hydrophilic drug, we previously designed viscous core liposomes. We aimed in this work to evaluate if these viscous core liposomes (NvcLs) could be of interest for siRNA encapsulation. Then, we sought to add a limited amount of positive charges to provide cell interaction and transfection. Cationic lipid dimyristoylaminopropylaminopropyl or the polymer poly(ethylenimine) were incorporated in NvcL to produce positively charged viscous core liposomes (PvcL) by a customized microfluidic device. We found that NvcLs increased the encapsulation efficiency and loading content with regards to the neutral liposome. Both PvcLPEI and PvcLDMAPAP exhibited transfection and GFP knock-down (≈40%) in both 2D and 3D cell cultures. Finally, the addition of slight positive charges did not induce cell toxicity. [ABSTRACT FROM AUTHOR]