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Chaperone-mediated autophagy (CMA) is involved in wild-type α-synuclein degradation in Parkinson’s disease (PD), and LAMP2A and Hsc 70 have recently been indicated to be deregulated by microRNAs. To recognize the regularory role of miR-320a in CMA and the possible role in α-synuclein degradation, in the present study, we examined the targeting and regulating role of miR-320 in Hsc 70 expression. We first constructed an α-synuclein-overexpressed human neuroblastoma cell line, SH-SY5Y-Syn(+), stably over-expressing wild-type α-synuclein and sensitive to an autophagy inhibitor, which exerted no effect on the expression of LAMP2A and Hsc 70. Then we evaluated the influence on the CMA by miR-320a in the SH-SY5Y-Syn(+) cells. It was shown that miR-320a mimics transfection of specifically targeted Hsc 70 and reduced its expression at both mRNA and protein levels, however, the other key CMA molecule, LAMP2A was not regulated by miR-320a. Further, the reduced Hsc 70 attenuated the α-synuclein degradation in the SH-SY5Y-Syn(+) cells, and induced a significantly high level of α-synuclein accumulation. In conclusion, we demonstrate that miR-320a specifically targeted the 3' UTR of Hsc 70, decreased Hsc 70 expression at both protein and mRNA levels in α-synuclein-over-expressed SH-SY5Y cells, and resulted in significant α-synuclein intracellular accumulation. These results imply that miR-320a might be implicated in the α-synuclein aggravation in PD.

Within the last two decades, a series of novel therapeutic nucleic acids entered research and clinical evaluation. Their differences both in biophysical properties as well as in mode and site of biological action provide polymer-based carriers with new delivery challenges. Recent tailor-made designs of polymeric carriers are reviewed that were optimized for nucleic acid cargos such as plasmid DNA, siRNA, and micro RNA, mRNA, or genome-modifying nucleic acids. The specific requirements for the various therapeutic cargos are discussed. Future directions include dynamic bioresponsive polymers as components of nanomachines, multifunctional sequence-defined carriers for evolution-based selective optimization, and organic−inorganic multicomponent nanoassemblies.

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The programmable endonuclease activity and simple usage of CRISPR/Cas9 have revolutionized the field of genome editing. The binding of single guide RNA (sgRNA) by the Cas9 protein results in the formation of negatively charged ribonucleoprotein (RNP) complexes. The presence of this functional complex inside cells is imperative for the intended specific genome modifications. The direct intracellular delivery of Cas9/sgRNA RNP complexes is of great advantage. In this work, a compound library of sequence-defined oligo­(ethylenamino) amides containing structural motifs for stable nanoparticle formation, cellular uptake, and endosomal release was used for the screening and development of suitable Cas9 RNP delivery vehicles. Lipid-containing oligoaminoamides (lipo-OAAs) were identified as the most efficient carriers for intracellular Cas9/sgRNA delivery and gene disruption. Fluorescence correlation spectroscopy measurements indicated that the lipo-OAAs only interact with sgRNA-loaded Cas9 protein, which suggests exclusive ionic interaction with the negatively charged RNPs. The type of contained fatty acid turned out to have a critical impact on the knock out efficiency: the presence of one hydroxy group in the fatty acid dramatically changes the properties and performance of the resulting Cas9/sgRNA lipo-OAA complexes. The lipo-OAA-containing hydroxy-stearic acid (OHSteA) was superior to the analogues with saturated or unsaturated fatty acids without hydroxylation; it formed smaller and more defined nanoparticles with Cas9/sgRNA and improved the cellular uptake and endosomal release, which altogether resulted in an increased nuclear association and the highest gene knock out levels. The efficient and adaptable delivery platform has high potential for the future development of therapeutics based on precise genome modifications.

A novel strategy for preparing universal antifogging and antimicrobial coating is reported by the means of one-step coating and Ag nanoparticle (AgNP) formation in situ. A series of hydrophilic glycopolymers including poly(N-3,4-dihydroxybenzenethyl methacrylamide-co-2-deoxy-2-(methacrylamido)glucopyranose) (P1s) and poly(N-3,4-dihydroxybenzenethyl methacrylamide-co-methacrylic acid-co-2-deoxy-2-(methacrylamido)glucopyranose) (P2s) were synthesized by sunlight-induced reverse addition− fragmentation chain transfer (RAFT) polymerization. With the ability to strongly immobilize onto organic and inorganic surfaces (i.e., glass slide, silicon wafer, and polycarbonate) via catechol groups, P1s are very convenient to form superhydrophilic and transparent thin coatings, which result in a unique antifogging property. Additionally, the antimicrobial property is realized by in situ AgNPs forming P2 coatings, facilitated by the presence of carboxyl groups and catechol groups in the polymer chain, rendering it superior antimicrobial activity against both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus microorganisms. This antifogging and antimicrobial thin coating shows strong prospects in medical and optical devices, with the extra benefits of avoiding potential pathogen infection in vitro or while in storage.

Glycopolymers attached to a surface possess the ability to bind to certain carbohydrate binding proteins in a highly specific manner, and because of this, the fabrication of glycopolymer-modified surfaces has evolved as an effective route toward bioresponsive systems. Poly(N-3,4-dihydroxybenzenethyl methacrylamide-co-2-(methacrylamido) glucopyranose) copolymers, containing sugar and catechol functionalities, are for the first time successfully prepared in a well-controlled manner via room temperature single-electron transfer initiation and propagation through radical addition fragmentation chain transfer technique. The polymerization behavior is investigated and it presents controlled features with first-order kinetics and linear relationships between molecular weights and monomer conversions. Moreover, the copolymers are used to modify different types of surfaces (silicon, steel, and plastic), the properties of the surfaces and the specific lectin-binding abilities are investigated by a combination of water contact angle, Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectra, scanning electron microscopy with energy dispersive X-ray (SEM/EDX), atomic force microscopy, and confocal microscope measurements.

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