The intracellular fate of an amphipathic pH-responsive polymer: Key characteristics towards drug delivery.

Biopolymers have become important drug delivery systems for therapeutic molecules by enhancing their accessibility and efficacy intracellularly. However, the transport of these drugs across the cell membrane and their release into the cytosol remain a challenge. The trafficking of poly (l-lysine iso-phthalamide) grafted with phenylalanine (PP-50) was investigated using an osteosarcoma cell line (SAOS-2). Colocalisation of this amphipathic biopolymer with endocytosis tracers, such as transferrin and lactosylceramide, suggested that PP-50 is partially internalised by both clathrin and caveolin-mediated endocytosis. Macropinocytosis was also investigated, but a smaller correlation was found between this mechanism and PP-50 transport. A significant decrease in polymer-mediated calcein uptake was found when cells were pre-incubated with endocytosis inhibitors, suggesting also the use of a combination of mechanisms for cell internalisation. In addition, PP-50 colocalisation with endosome and lysosome pathway markers showed that the polymer was able to escape the endolysosomal compartment before maturation. This is a critical characteristic of a biopolymer towards use as drug delivery systems and biomedical applications.Agency for Science and Technology Research, CONICYT (Chile) (Studentship)This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.msec.2016.08.00

Tuning the Endocytosis Mechanism of Zr-Based Metal–Organic Frameworks through Linker Functionalization

A critical bottleneck for the use of metal-organic frameworks (MOFs) as drug delivery systems has been allowing them to reach their intracellular targets without being degraded in the acidic environment of the lysosomes. Cells take up particles by endocytosis through multiple biochemical pathways, and the fate of these particles depends on these routes of entry. Here, we show the effect of functional group incorporation into a series of Zr-based MOFs on their endocytosis mechanisms, allowing us to design an effi-cient drug delivery system. In particular, naphthalene-2,6-dicarboxylic acid and 4,4'-biphenyldicarboxylic acid ligands promote entry through the caveolin-pathway, allowing the particles to avoid lysosomal degradation and be delivered into the cytosol, en-hancing their therapeutic activity when loaded with drugs.C.A.O. thanks Becas Chile and the Cambridge Trust for funding. S.H. thanks the Cambridge Trust for funding. R.S.F. and D.F.-J. thank the Royal Society for the receipt of University Research Fellowships. D.F.-J. thanks financial support from ERC-2016-COG 726380. R.S.F., R.J.M., and I.A.L. thank the University of Glasgow and the EPSRC (EP/L004461/1) for funding. G.B., I.I., and D.M. acknowledge the financial support from 2014-SGR-80, MAT2015-65354-C2-1-R and EU FP7 ERC-Co 615954. ICN2 received support from the Spanish MINECO through the Severo Ochoa Centers of Excellence Program, under Grant No. SEV-2013-0295

Current trend in synthesis, Post-Synthetic modifications and biological applications of Nanometal-Organic frameworks (NMOFs)

Since the early reports of MOFs and their interesting properties, research involving these materials has grown wide in scope and applications. Various synthetic approaches have ensued in view of obtaining materials with optimised properties, the extensive scope of application spanning from energy, gas sorption, catalysis biological applications has meant exponentially evolved over the years. The far‐reaching synthetic and PSM approaches and porosity control possibilities have continued to serve as a motivation for research on these materials. With respect to the biological applications, MOFs have shown promise as good candidates in applications involving drug delivery, BioMOFs, sensing, imaging amongst others. Despite being a while away from successful entry into the market, observed results in sensing, drug delivery, and imaging put these materials on the spot light as candidates poised to usher in a revolution in biology. In this regard, this review article focuses current approaches in synthesis, post functionalization and biological applications of these materials with particular attention on drug delivery, imaging, sensing and BioMOFs