Primitive selection of the fittest emerging through functional synergy in nucleopeptide networks

Many fundamental cellular and viral functions, including replication and translation, involve complex ensembles hosting synergistic activity between nucleic acids and proteins/peptides. There is ample evidence indicating that the chemical precursors of both nucleic acids and peptides could be efficiently formed in the prebiotic environment. Yet, studies on nonenzymatic replication, a central mechanism driving early chemical evolution, have focused largely on the activity of each class of these molecules separately. We show here that short nucleopeptide chimeras can replicate through autocatalytic and cross-catalytic processes, governed syn-ergistically by the hybridization of the nucleobase motifs and the assembly propensity of the peptide segments. Unequal assembly-dependent replication induces clear selectivity toward the formation of a certain species within small networks of complementary nucleopeptides. The selectivity pattern may be influenced and indeed maximized to the point of almost extinction of the weakest replicator when the system is studied far from equilibrium and manipulated through changes in the physical (flow) and chemical (template and inhibition) conditions. We postulate that similar processes may have led to the emergence of the first functional nucleic-acid-peptide assemblies prior to the origin of life. Furthermore, spontaneous formation of related replicating complexes could potentially mark the initiation point for information transfer and rapid progression in complexity within primitive environments, which would have facilitated the development of a variety of functions found in extant biological assembliesThe research was supported by the H2020 FET-Open (A.d.l.E and G.A.; CLASSY project, Grant Agreement Nº 862081), an NSF-BSF grant (GA; BSF-2015671), and the Spanish Ministry of Economy and Competitivity (A.d.l.E; MINECO: CTQ-2014-53673-P, CTQ-2017-89539-P, and EUIN2017-87022). The European COST Action CM1304 funded a Short-Term Scientific Mission of S.M.R. to BGU. A.K.B. received support from the BGU Kreitmann fellowships progra

Mesoporous Silica Particles as Drug Delivery Systems—The State of the Art in Loading Methods and the Recent Progress in Analytical Techniques for Monitoring These Processes

Conventional administration of drugs is limited by poor water solubility, low permeability, and mediocre targeting. Safe and effective delivery of drugs and therapeutic agents remains a challenge, especially for complex therapies, such as cancer treatment, pain management, heart failure medication, among several others. Thus, delivery systems designed to improve the pharmacokinetics of loaded molecules, and allowing controlled release and target specific delivery, have received considerable attention in recent years. The last two decades have seen a growing interest among scientists and the pharmaceutical industry in mesoporous silica nanoparticles (MSNs) as drug delivery systems (DDS). This interest is due to the unique physicochemical properties, including high loading capacity, excellent biocompatibility, and easy functionalization. In this review, we discuss the current state of the art related to the preparation of drug-loaded MSNs and their analysis, focusing on the newest advancements, and highlighting the advantages and disadvantages of different methods. Finally, we provide a concise outlook for the remaining challenges in the field