Exosome-mimetic nanoplatforms for targeted cancer drug delivery.

BACKGROUND: Lack of effective tumor-specific delivery systems remains an unmet clinical challenge for successful translation of innovative therapies, such as, therapeutic oligonucleotides. In the past decade, exosomes have been suggested to be ideal drug delivery systems with application in a broad range of pathologies including cancer, due to their organotropic properties. Tumor-derived exosomes, having tumor-homing properties, can efficiently reach cancer cells and therefore behave as carriers for improved drug delivery to the primary tumor and metastases. However, due to their complex composition, and still undefined biological functions, safety concerns arise hampering their translation to the clinics. RESULTS: We propose here the development of exosome-mimetic nanosystems (EMNs) that simulate natural tumor-derived exosomes with respect to their structure and functionality, but with a controlled composition, for the targeted delivery of therapeutic oligonucleotides to lung adenocarcinoma cells (microRNA-145 mimics). Making use of the well-known liposome technology, EMNs can be engineered, loaded with the therapeutic compounds, and tailored with specific proteins (integrin α6ß4) providing them organotropic properties. EMNs show great similarities to natural exosomes with respect to their physicochemical properties, drug loading capacity, and ability to interact with the cancer target cells in vitro and in vivo, but are easier to manufacture, can be produced at high yields, and are safer by definition. CONCLUSIONS: We have designed a multifunctional nanoplatform mimicking exosomes, EMNs, and proved their potential to reach cancer cells with a similar efficient that tumor-derived exosomes but providing important advantages in terms of production methodology and regulations. Additionally, EMNs are highly versatile systems that can be tunable for a broader range of applications.

Manganese Ferrite Nanoparticles Encapsulated into Vitamin E/Sphingomyelin Nanoemulsions as Contrast Agents for High-Sensitive Magnetic Resonance Imaging.

Magnetic resonance imaging (MRI) is one of the most powerful non-invasive imaging modalities used in clinics due to its great spatial resolution and excellent soft-tissue contrast, though still less sensitive than other techniques such as the nuclear imaging modalities. This lack of sensitivity can be improved with the use of contrast agents based on nanomaterials. In recent years, researchers have focused on the development of magnetic nanoparticles, given their role as enhancers of the contrast signal based on the magnetic resonance. Manganese ferrite nanoparticles stand out, given their high magnetic susceptibility and magnetic soft nature. Herein, 10 nm MnFe2 O4 nanoparticles, functionalized with the natural antioxidant vitamin E (VitE-MFO) are encapsulated into simple, biodegradable and non-toxic nanoemulsions (NEs), by a reproducible one-step method obtaining stable 150 nm-sized magnetic nanoemulsions (VitE-MFO-NEs). After encapsulation, the superparamagnetic properties of VitE-MFO are maintained and MR imaging studies reveal an extremely high transverse relaxivity for VitE-MFO-NEs (652.9 × 10-3  m-1  s-1 ), twofold higher than VitE-MFO value. Moreover, VitE-MFO-NEs show great in vivo biocompatibility and good signal in in vivo and ex vivo MRI, which indicates their great potential for biomedical imaging enhancing the negative MR contrast and significantly improving the sensitivity of MRI.