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Neuroblastoma (NB) is a solid tumor occurring in infancy and childhood. Its high-risk form has currently a survival rate <50%, despite aggressive treatments. This worrying scenario is worsened by drug-induced secondary tumorigenesis and the emergency of drug resistance, calling for the urgent development of new extra-genomic treatments. Triphenyl phosphonium salts (TPPs) are mitochondria-targeting compounds that exert anticancer effects, impair mitochondria functions, and damage DNA at the same time. Despite several biochemical applications, TPP-based bola-amphiphiles self-assembling nanoparticles (NPs) in water have never been tested as antitumor agents. Here, with the aim of developing new antitumor devices to also counteract resistant forms of HR-NB, the anticancer effects of a TPP-based bola-amphiphile molecule have been investigated in vitro for the first time. To this end, we considered the previously synthesized and characterized sterically hindered quaternary phosphonium salt (BPPB). It embodies both the characteristics of mitochondria-targeting compounds and those of bola-amphiphiles. The anticancer effects of BPPB were assessed against HTLA-230 human stage-IV NB cells and their counterpart, which is resistant to etoposide (ETO), doxorubicin (DOX), and many other therapeutics (HTLA-ER). Very low IC50 values of 0.2 µM on HTLA-230 and 1.1 µM on HTLA-ER (538-fold lower than that of ETO) were already determined after 24 h of treatment. The very low cell viability observed after 24 h did not significantly differ from that observed for the longest exposure timing. The putative future inclusion of BPPB in a chemotherapeutic cocktail for HR-NB was assessed by investigating in vitro its cytotoxic effects against mammalian cell lines. These included monkey kidney cells (Cos-7, IC50 = 4.9 µM), human hepatic cells (HepG2, IC50 = 9.6 µM), a lung-derived fibroblast cell line (MRC-5, IC50 = 2.8 µM), and red blood cells (RBCs, IC50 = 14.9 µM). Appreciable to very high selectivity indexes (SIs) have been determined after 24 h treatments (SIs = 2.5–74.6), which provided evidence that both NB cell populations were already fully exterminated. These in vitro results pave the way for future investigations of BPPB on animal models and upon confirmation for the possible development of BPPB as a novel therapeutic to treat MDR HR-NB cells. [ABSTRACT FROM AUTHOR]

Dendrimers are appealing scaffolds for creating carbohydrate mimics with unique multivalent cooperativity. We report here novel bola‐amphiphilic glycodendrimers bearing mannose and glucose terminals, and a hydrophobic thioacetal core responsive to reactive oxygen species. The peculiar bola‐amphiphilic feature enabled stronger binding to lectin compared to conventional amphiphiles. In addition, these dendrimers are able to target mannose receptors and glucose transporters expressed at the surface of cells, thus allowing effective and specific cellular uptake. This highlights their great promise for targeted delivery. [ABSTRACT FROM AUTHOR]

A facile and flexible chemoenzymatic route for the preparation of a variety of amino acid-based surfactants ranging from simple monoesters to more complex bola- and gemini-amphiphiles is described. The methodology is based on the observation that some lipases, notably immobilized Candida antarctica and Rhizomucor miehei, readily accept N-Cbzamino acids as substrates and catalyze their esterification/amidation with long-chain alcohols and α,ω-diols/α,ω-diamines in excellent yield. The resulting alkanediyl-α,ω-bis-( N-Cbz-amino acid) can be either deprotected using conventional procedures to attain a number of multifunctional bola-amphiphiles or further modified to obtain a range of amino acid-based gemini surfactants. [ABSTRACT FROM AUTHOR]

The architecture of Zn-Al layered double hydroxides (LDHs), organo-modified with bola-amphiphiles molecules, is matching its interlayer space to the size of narrow-band red-emitting InP/ZnS core-shell quantum dots (QDs) to form original high-performance functional organic-inorganic QD-bola-LDH hybrids. The success of size-matching interlayer space (SMIS) approach is confirmed by X-ray diffraction, small angle X-ray scattering (SAXS), TEM, STEM-HAADF, and photoluminescence investigations. The QD-Bola-LDH hybrid exhibits a photoluminescence quantum yield three times higher than that of pristine InP/ZnS QDs and provides an easy dispersion into silicone-based resins, what makes the SMIS approach a change of paradigm compared to intercalation chemistry using common host structures. Moreover, this novel hybrid presents low QD-QD energy transfer comparable to that obtained for QDs in suspension. Composite silicone films incorporating InP/ZnS (0.27 wt%) QD-bola-LDH hybrids further show remarkable improved photostability relative to pristine QDs. An LED overlay consisting of a blue LED chip and silicone films loaded with QD-bola-LDH hybrids and YAG:Ce phosphors exhibits a color rendering index close to 94., (© 2021 Wiley-VCH GmbH.)

The development of new nonviral vectors with high transfection efficiency and low cyto-toxicity remains a great challenge in the field of small interfering RNA delivery. To address the challenge, we developed two cationic amphiphilic carriers, octa-arginine double-substituted (R8-bibola) and octa-arginine monosubstituted (R8-monobola), based on transmembrane peptide-octa-arginine (R8) for complexing siRNA (R8-bola/siRNA). To further improve the stability of the nanocomplexes and tumor targeting, HA-R8-bola/siRNA nanocomplexes were prepared by surface modification of R8-bola/siRNA with hyaluronic acid (HA). In vitro experiments showed that R8-bibola has better biocompatibility than R8-monobola, which effectively increased the cell uptake of siRNA and improved the Bcl-2 protein silencing efficiency. In vivo antitumor experiments confirmed that the HA-modified nanocomplexes effectively inhibited tumor growth by silencing Bcl-2 protein expression. The new bola-type nanoparticles provide a new strategy to improve the delivery efficiency of siRNA for tumor treatment.