Giant amphiphiles encompassing a hydrophilic β-cyclodextrin (βCD) component and a hydrophobic calix[4]arene (CA4) module undergo self-assembly in aqueous media to afford core-shell nanospheres or nanocapsules, depending on the nanoprecipitation protocol, with high docetaxel (DTX) loading capacity. The blank and loaded nanoparticles have been fully characterized by dynamic light scattering (DLS), ζ-potential measurements and cryo-transmission electron microscopy (cryo-TEM). The data are compatible with the distribution of the drug between the nanoparticle core and the shell, where it is probably anchored by inclusion of the DTX aromatic moieties in βCD cavities. Indeed, the release kinetics profiles evidenced an initial fast release of the drug, which likely accounts for the fraction hosted on the surface, followed by a slow and sustained release rate, corresponding to diffusion of DTX in the core, which can be finely tuned by modification of the giant amphiphile chemical structure. The ability of the docetaxel-loaded nanoparticles to induce cellular death in different prostate (human LnCap and PC3) and glioblastoma (human U87 and rat C6) cells was also explored. Giant amphiphile-based DTX formulations surpassing or matching the antitumoral activity of the free DTX formulation were identified in all cases with no need to employ any organic co-solvent, thus overcoming the DTX water solubility problems. Moreover, the presence of the βCD shell at the surface of the assemblies is intended to impart stealth properties against serum proteins while permitting nanoparticle surface decoration by supramolecular approaches, paving the way for a new generation of molecularly well-defined antitumoral drug delivery systems with improved specificity and efficiency. Altogether, the results provide a proof of concept of the suitability of the approach based on βCD-CA4 giant amphiphiles to access DTX carriers with tunable properties.

Alzheimer’s disease (AD) is one of the main causes of disability and dependency among elderly people. AD is a neurodegenerative disorder characterized by a progressive and irreversible cognitive impairment, whose etiology is unclear because of the complex molecular mechanisms involved in its pathophysiology. A global view of the AD pathophysiology is described in order to understand the need for an effective treatment and why nanoparticles (NPs) could be an important weapon against neurodegenerative diseases by solving the general problem of poor delivery into the central nervous system (CNS) for many drugs. Drug delivery into the CNS is one of the most challenging objectives in pharmaceutical design, due to the limited access to the CNS imposed by the blood-brain barrier (BBB). The purpose of this review is to present a comprehensive overview of the use of NPs as delivery systems for therapeutic and diagnostic purposes in models of AD.

Synthetic double-stranded small interfering RNAs (siRNAs) mimic interference RNAs (RNAi) and can bind target mRNAs with a high degree of specificity, leading to selective knockdown of the proteins they encode. However, siRNAs are very labile and must be both protected and transported by nanoparticles to be efficiently delivered into cells. In this work, we used a Janus-type polycationic amphiphilic β-cyclodextrin derivative to efficiently transfect siRNAs targeting mRNAs encoding mitogen-activated protein kinase (p42-MAPK) or Ras homolog enriched in brain (Rheb) into different cancer cell lines as well as astrocytes. We took advantage of this high transfection efficiency to simultaneously knock down p42-MAPK and Rheb to boost docetaxel (DTX)-mediated toxicity in two human prostate cancer cell lines (LNCaP and PC3). We found that double knockdown of p42-MAPK and Rheb increased DTX-toxicity in LNCaP but not in PC3 cells. However, we also observed the same effect when scramble siRNA was used, therefore pointing to an off-target effect. Indeed, we found that the siRNA we used in this work induced toll-like receptor 3 activation, leading to β-interferon production and caspase activation. We believe that this mechanism could be very useful as a general strategy to elicit an immune response against prostate cancer cells.