Efficient cellular delivery of biologically active molecules is one of the key factors that affect the discovery and development of novel drugs. The plasma membrane is the first barrier that prevents direct translocation of chemic entities, and thus obstructs their efficient intracellular delivery. Generally, hydrophilic small molecule drugs are poor permeability that reduce bioavailability and thus limit the clinic application. The cellular uptake of macromolecules and drug carriers is very inefficient without external assistance. Therefore, it is desirable to develop potent delivery systems for achieving effective intracellular delivery of chemic entities. Apart from of the types of delivery strategies, the composition of the cell membrane is critical for delivery efficiency due to the fact that cellular uptake is affected by the interaction between the chemical entity and the plasma membrane. In this review, we aimed to develop a profound understanding of the interactions between delivery systems and components of the plasma membrane. For the purpose, we attempt to present a broad overview of what delivery systems can be used to enhance the intracellular delivery of poorly permeable chemic entities, and how various delivery strategies are applied according to the components of plasma membrane.

Protein/antibody therapeutics have exhibited the advantages of high specificity and activity even at an extremely low concentration compared to small molecule drugs. However, they are accompanied by unfavorable physicochemical properties such as fragile tertiary structure, large molecular size, and poor penetration of the membrane, and thus the clinical use of protein drugs is hindered by inefficient delivery of proteins into the host cells. To overcome the challenges associated with protein therapeutics and enhance their biopharmaceutical applications, various protein‐loaded nanocarriers with desired functions, such as lipid nanocapsules, polymeric nanoparticles, inorganic nanoparticles, and peptides, are developed. In this review, the different strategies for intracellular delivery of proteins are comprehensively summarized. Their designed routes, mechanisms of action, and potential therapeutics in live cells or in vivo are discussed in detail. Furthermore, the perspective on the new generation of delivery systems toward the emerging area of protein‐based therapeutics is presented as well.

Mitochondria are the powerhouse of cells. They are vital organelles that maintain cellular function and metabolism. Dysfunction of mitochondria results in various diseases with a great diversity of clinical appearances. In the past, strategies have been developed for fabricating subcellular‐targeting drug‐delivery nanocarriers, enabling cellular internalization and subsequent organelle localization. Of late, innovative strategies have emerged for the smart design of multifunctional nanocarriers. Hierarchical targeting enables nanocarriers to evade and overcome various barriers encountered upon in vivo administration to reach the organelle with good bioavailability. Stimuli‐responsive nanocarriers allow controlled release of therapeutics to occur at the desired target site. Synergistic therapy can be achieved using a combination of approaches such as chemotherapy, gene and phototherapy. In this Review, we survey the field for recent developments and strategies used in the smart design of nanocarriers for mitochondria‐targeted therapeutics. Existing challenges and unexplored therapeutic opportunities are also highlighted and discussed to inspire the next generation of mitochondrial‐targeting nanotherapeutics.

MicroRNAs are small regulatory noncoding RNAs that regulate various biological processes. Herein, we will present the development of the strategies for intracellular miRNAs delivery, and specially focus on the rational designed routes, their mechanisms of action, as well as potential therapeutics used in the host cells or in vivo studies.

Highlights Chitosan-coated nanocapsules, but not nanoemulsions, influence the -potential of E.coli  A fixed number of nanocapsules binds and promotes aggregation of bacteria  In silico simulations agree closely with experimental results  Chitosan-coated nanocapsules attenuate the bacterial quorum sensing response § These authors contributed equally to this publication * Author for correspondence Colloids and Surfaces B: Biointerfaces 149 (2017) 358-368 AbstractWe examined the interaction between chitosan-based nanocapsules (NC), with average hydrodynamic diameter ~114-155 nm, polydispersity ~0.127, and -potential ~+50 mV, and an E. coli bacterial quorum sensing reporter strain. Dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) allowed full characterization and assessment of the absolute concentration of NC per unit volume in suspension. By centrifugation, DLS, and NTA, we determined experimentally a "stoichiometric" ratio of ~80 NC/bacterium. By SEM it was possible to image the aggregation between NC and bacteria. Moreover, we developed a custom in silico platform to simulate the behavior of particles with diameters of 150 nm and -potential of +50 mV on the bacterial surface. We computed the detailed force interactions between NC-NC and NC-bacteria and found that a maximum number of 145 particles might interact at the bacterial surface. Additionally, we found that the "stoichiometric" ratio of NC and bacteria has a strong influence on the bacterial behavior and influences the quorum sensing response, particularly due to the aggregation driven by NC.

Decellularized human dermis has been used for a number of clinical applications including wound healing, soft tissue reconstruction, and sports medicine procedures. A variety of methods exist to prepare this useful class of biomaterial. Here, we describe a decellularization technology (MatrACELL®) utilizing a non-denaturing anionic detergent, N-Lauroyl sarcosinate, and endonuclease, which was developed to remove potentially immunogenic material while retaining biomechanical properties. Effective decellularization was demonstrated by a residual DNA content of ≤4 ng/mg of wet weight which represented >97 % DNA removal compared to unprocessed dermis. Two millimeter thick MatrACELL processed human acellular dermal matrix (MH-ADM) exhibited average ultimate tensile load to failure of 635.4 ± 199.9 N and average suture retention strength of 134.9 ± 55.1 N. Using an in vivo mouse skin excisional model, MH-ADM was shown to be biocompatible and capable of supporting cellular and vascular in-growth. Finally, clinical studies of MH-ADM in variety of applications suggest it can be an appropriate scaffold for wound healing, soft tissue reconstruction, and soft tissue augmentation.

The objective of this study was to delay the rate and extent of gastric destabilization of emulsions using composite particle-particle layers at the O/W interface. Pickering emulsions (20 wt% oil) were prepared using lactoferrin nanogel particles (LFN, Dh=100 nm) (1 wt%) or a composite layer of LFN and inulin nanoparticles, latter was enzymatically synthetized by inulosucrase IslA from Leuconostoc citreum (INP) (Dh=116±1 nm) (1 wt% LFN 3 wt% INP). The hypothesis was that creating a secondary layer of biopolymeric particles might act as a barrier to pepsin to access the underlying proteinaceous particles. Droplet size, microscopy (optical and transmission electron microscopy (TEM)),-potential and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) were used to understand the colloidal fate of these Pickering emulsions in an in vitro gastric model (pH 3, 37 C, pepsin). The-potential measurements and TEM images confirmed that LFN and INP were at the O/W interface, owing to the electrostatic attraction between oppositely charged LFN (+29.3±0.7 mV) and INP (-10±1.8 mV) at both neutral and gastric pH. The SDS-PAGE results revealed that adsorbed LFN was less prone to pepsinolysis as compared to a typical protein monolayer at the interface. Presence of INP further decreased the rate and degree of hydrolysis of the LFN (>65% intact protein remaining after 60 min of digestion) by acting as a steric barrier to the diffusion of pepsin and inhibited droplet coalescence. Thus, composite particle-particle layers (LFN + INP) at droplet surface shows potential for rational designing of gastric-stable food and pharmaceutical applications.

Special AT-rich sequence-binding protein 1 (SATB1) is a global chromatin organizer and gene regulator, and high expression of SATB1 is associated with progression and poor prognosis in several malignancies. Here, we examine the expression pattern of SATB1 in glioma. Microarray analysis of 127 clinical samples showed that SATB1 mRNA was expressed at lower levels in highly malignant glioblastoma multiforme (GBM) than in low-grade glioma and normal brain tissue. This result was further confirmed by real-time RT-PCR in the clinical samples, three GBM cell lines, primary SU3 glioma cells and tumor cells harvested by laser-capture microdissection. Consistent with the mRNA levels, SATB1 protein expression was downregulated in high-grade glioma, as shown by western blotting. However, phospho-SATB1 levels showed an opposite pattern, with a significant increase in these tumors. Immunohistochemical analysis of phospho-SATB1 expression in tissue microarrays with tumors from 122 glioma cases showed that phospho-SATB1 expression was significantly associated with high histological grade and poor survival by Kaplan–Meier analysis. In vitro transfection analysis showed that phospho-SATB1 DNA binding has a key role in regulating the proliferation and invasion of glioma cells. The effect of SATB1 in glioma cell is mainly histone deacetylase (HDAC1)-dependent. We conclude that phospho-SATB1, but not SATB1 mRNA expression, is associated with the progression and prognosis of glioma. By interaction with HDAC1, phospho-SATB1 contributes to the invasive and proliferative phenotype of GBM cells.