Protein-based targeted toxins play an increasingly important role in targeted tumor therapies. In spite of their high intrinsic toxicity, their efficacy in animal models is low. A major reason for this is the limited entry of the toxin into the cytosol of the target cell, which is required to mediate the fatal effect. Target receptor bound and internalized toxins are mostly either recycled back to the cell surface or lysosomally degraded. This might explain why no antibody-targeted protein toxin has been approved for tumor therapeutic applications by the authorities to date although more than 500 targeted toxins have been developed within the last decades. To overcome the problem of insufficient endosomal escape, a number of strategies that make use of diverse chemicals, cell-penetrating or fusogenic peptides, and light-induced techniques were designed to weaken the membrane integrity of endosomes. This review focuses on glycosylated triterpenoids as endosomal escape enhancers and throws light on their structure, the mechanism of action, and on their efficacy in cell culture and animal models. Obstacles, challenges, opportunities, and future prospects are discussed.

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Polymers occupy an important and omnipresent role in our current society. Because of the large-scale access and the straightforward adjustability of the properties of polymeric materials, countless applications have been realized in the past and an increased demand is proposed for the future. [1][2][3][4][5] Although there has been great success in polymer chemistry, the origin of the monomers remains a major issue as polymers are currently based on the steadily decreasing fossil fuel feedstock. [6][7][8][9][10] Moreover, huge amounts of end-of-life polymeric materials are produced every year in a multi-ton scale. The current waste management system is based mainly on landfill storage, thermal recycling (thermal decomposition for energy purposes), and down-cycling to produce low-quality materials. [11][12][13][14] Noteworthy, only a small fraction is recycled through depolymerization to obtain monomers or suitable synthons, which can later be polymerized to high-quality materials to close the cycle.End-of-life polymers can be a potential feedstock for new polymers. To realize such recycling systems, the application of catalysis offers the possibility to perform depolymerization procedures in an efficient and sustainable manner, to reduce energy costs, and to create economic advantages (Scheme 1). [15, 16] Recently, we reported on a low-temperature depolymerization process of manmade polyethers [e.g., polytetrahydrofuran (polyTHF), polyethylene oxide, and polypropylene oxide] to produce suitable compounds as potential starting materials for polymerization chemistry. In the presence of catalytic amounts of zinc or iron salts, polyethers were easily converted with acid chlorides under non-inert and solvent-free conditions. [17][18][19] However, stoichiometric amounts of acid chlorides were necessary to perform the depolymerization, and a protocol without additional reagents would be more beneficial with respect to energy consumption and cost. In this regard, polyTHF can be easily synthesized through ring-opening polymerization (ROP) of tetrahydrofuran (THF), potentially via tetrahydrofuranium ions, in the presence of suitable catalysts (e.g., Brønsted or Lewis acids). [20,21] Interestingly, an equilibrium between ROP and ring-closing depolymerization has been discussed. Based on that, we wondered if it was possible to perform the ring-closing depolymerization to produce THF as only product, which could then be reused as a monomer in polymerization chemistry (Scheme 1). Interestingly, in patent literature a few processes for the depolymerization of polyTHF to produce THF have been accounted, for example by applying yttrium triflate, ytterbium triflate supported on silica-alumina, Kaolin, zeolite, aluminum silicate, or sulfuric acid as pre-catalysts. [22][23][24][25][26][27][28] Based on the reported protocols, the selection of the catalyst was of great importance to perform the reaction with high activity and suitable conditions. Moreover, the availability and the cost of the catalyst materials were of significance....

Targeted tumor therapy can provide the basis for the inhibition of tumor growth. However, a number of toxin-based therapeutics lack efficacy because of insufficient endosomal escape after being internalized by endocytosis. To address this problem, the potential of glycosylated triterpenoids, such as SO1861, as endosomal escape enhancers (EEE) for superparamagnetic iron oxide nanoparticle (SPION)-based toxin therapy was investigated. Herein, two different SPION-based particle systems were synthesized, each selectively functionalized with either the targeted toxin, dianthin-epidermal growth factor (DiaEGF), or the EEE, SO1861. After applying both particle systems in vitro, an almost 2000-fold enhancement in tumor cell cytotoxicity compared to the monotherapy with SPION-DiaEGF and a 6.7-fold gain in specificity was observed. Thus, the required dose of the formulation was appreciably reduced, and the therapeutic window widened.