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There is considerable interest in developing a common, universal platform for delivering biomacromolecules such as proteins and RNAs into diverse cells with high efficiency. Here, it is shown that carbon nanosyringe arrays (CNSAs) under an applied centrifugal g-force (cf-CNSAs) can deliver diverse bioactive cargos directly into the cytosol of hard-to-transfect cells with relatively high efficiency and reproducibility. The cf-CNSA platform, an optimized version of a previous CNSA-mediated intracellular delivery platform that adds a g-force feature, exhibits more rapid and superior delivery of cargos to various hard-to-transfect cells than is the case in the absence of g-force. Active species, including small interfering RNAs, plasmids, and proteins are successfully transported across plasma membrane barriers into various cells. By overcoming the limitations of currently available transfection methods, the cf-CNSA platform paves the way to universal delivery of a variety of cargos, facilitating the analysis of cellular responses in diverse cell types., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A new oral delivery system for insulin was developed aiming to improve bioavailability based on a conjugate between insulin and low molecular weight chitosan (LMWC) of narrow molecular weight distribution. The conjugate was synthesized from the reaction between site-specifically modified insulin at the lysine residue of the B-chain and sulfhydryl-modified LMWC. To investigate the effect of MWs of LMWC on oral bioavailability of insulin, various LMWCs (3, 6, 9, and 13k average MW) with narrow MW distribution were used to synthesize LMWC-insulin conjugates. The content of insulin in the LMWC-insulin conjugates was calculated by UV spectrophotometer: 62%, 44%, 38%, and 29% for 3, 6, 9, and 13 kDa LMWC, respectively. The biological activity of insulin in LMWC(6k)-insulin conjugate in vivo was 43 ± 0.7%. LMWC-insulin conjugates after oral administration to diabetic rat models could control blood glucose levels effectively for several hours. Of those conjugates, LMWC(9k)-insulin exhibited the highest pharmacodynamic bioavailability of 3.7 ± 0.3% relative to that of subcutaneously (s.c.) injected insulin (100%).

Theranostic systems are receiving ever-increasing attention due to their potential therapeutic utility, imaging enhancement capability, and promise for advancing the field of personalized medicine, particularly as it relates to the diagnosis, staging, and treatment of cancer. In this Tutorial Review, we provide an introduction to the concepts of theranostic drug delivery effected via use of conjugates that are able to target cancer cells selectively, provide cytotoxic chemotherapeutics, and produce readily monitored imaging signals in vitro and in vivo. The underlying design concepts, requiring the synthesis of conjugates composed of imaging reporters, masked chemotherapeutic drugs, cleavable linkers, and cancer targeting ligands, are discussed. Particular emphasis is placed on highlighting the potential benefits of fluorogenic reaction-based targeted systems that are activated for both imaging and therapy by cellular entities, e.g., thiols, reactive oxygen species and enzymes, which are present at relatively elevated levels in tumour environments, physiological characteristics of cancer, e.g., hypoxia and acidic pH. Also discussed are systems activated by an external stimulus, such as light. The work summarized in this Tutorial Review will help define the role fluorogenic reaction-based, cancer-targeting theranostics may have in advancing drug discovery efforts, as well as improving our understanding of cellular uptake and drug release mechanisms. [ABSTRACT FROM AUTHOR]

Abstract: Targeted delivery of anticancer drugs to tumors has attracted considerable research interest because of its potential to reduce adverse toxicity while improving therapeutic efficacy. In this study, we synthesized and evaluated the therapeutic efficacy of a conjugate of a high-affinity peptide (aptide) and the anticancer drug docetaxel (DTX). A fibronectin extra domain B (EDB)-specific aptide (APTEDB) was used as a cancer-specific targeting ligand. An APTEDB–DTX conjugate was synthesized from an alkyne-modified aptide and azide-modified DTX via click chemistry. A microscopy study revealed selective binding of dye-labeled APTEDB to EDB-overexpressing cancer cells. The cytotoxicity of the conjugate toward EDB-overexpressing murine lung carcinoma (LLC) and human glioblastoma (U87MG) was similar to that of free DTX. In a pharmacokinetic study, APTEDB–DTX formulated with PEG400/ethanol(5%) exhibited a circulation half-life similar to that of a Tween-80/ethanol formulation of parent DTX. Finally, an evaluation of intravenously injected APTEDB–DTX in mice bearing EDB-positive tumors showed that APTEDB–DTX inhibited the growth of both LLC allograft and U87MG xenograft tumors with an efficacy better than the parent-DTX formulation but with much lower toxicity, as evidenced by reduced body weight loss. Taken together, these results indicate that the aptide–drug conjugate system described here may hold potential as a targeted therapy regimen. [Copyright &y& Elsevier]