Silencing RNA (siRNA) technologies emerge as a promising therapeutic tool for the treatment of multiple diseases. An ideal nanocarrier (NC) for siRNAs should be stable at physiological pH and release siRNAs in acidic endosomal pH, fulfilling siRNA delivery only inside cells. Here, we show a novel application of polyamine phosphate NCs (PANs) based on their capacity to load negatively charged nucleic acids and their pH stability. PANs are fabricated by complexation of phosphate anions from phosphate buffer solution (PB) with the amine groups of poly(allylamine) hydrochloride as carriers for siRNAs. PANs are stable in a narrow pH interval, from 7 to 9, and disassemble at pH's higher than 9 and lower than 6. siRNAs are encapsulated by complexation with poly(allylamine) hydrochloride before or after PAN formation. PANs with encapsulated siRNAs are stable in cell media. Once internalized in cells following endocytic pathways, PANs disassemble at the low endosomal pH and release the siRNAs into the cytoplasm. Confocal laser scanning microscopy (CLSM) images of Rhodamine Green labeled PANs (RG-PANs) with encapsulated Cy3-labeled siRNA in A549 cells show that siRNAs are released from the PANs. Colocalization experiments with labeled endosomes and either labeled siRNAs prove the translocation of siRNAs into the cytosol. As a proof of concept, it is shown that PANs with encapsulated green fluorescence protein (GFP) siRNAs silence GFP in A549 cells expressing this protein. Silencing efficacy was evaluated by flow cytometry, CLSM, and Western blot assays. These results open the way for the use of poly(allylamine) phosphate nanocarriers for the intracellular delivery of genetic materials.

BackgroundPhotodynamic therapy (PDT) combines light, molecular oxygen and a photosensitizer to induce oxidative stress in target cells. Certain hydrophobic photosensitizers, such as aluminium-phthalocyanine chloride (AlPc), have significant potential for antitumor PDT applications. However, hydrophobic molecules often require drug-delivery systems, such as nanostructures, to improve their pharmacokinetic properties and to prevent aggregation, which has a quenching effect on the photoemission properties in aqueous media. As a result, this work aims to develop and test the efficacy of an AlPc in the form of a nanoemulsion to enable its use in anticancer PDT.ResultsThe nanoemulsion was developed using castor oil and Cremophor ELP®, and a monodisperse population of nanodroplets with a hydrodynamic diameter of approximately 25 nm was obtained. While free AlPc failed to show significant activity against human breast adenocarcinoma MCF-7 cells in an in vitro PDT assay, the AlPc in the nanoemulsion showed intense photodynamic activity. Photoactivated AlPc exhibited a 50 % cytotoxicity concentration (CC50) of 6.0 nM when applied to MCF-7 cell monolayers and exerted a powerful cytotoxic effect on MCF-7 cell spheroids.ConclusionThrough the use of spontaneous emulsification, a stable AlPc nanoemulsion was developed that exhibits strong in vitro photodynamic activity on cancer cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-015-0095-3) contains supplementary material, which is available to authorized users.

No abstract

Taken together, these results indicate that SNEDDS-EPI is efficient in reducing worm burden in comparison to treatment with the free version of EPI. [Formula: see text].

No abstract