Hyaluronic acid for anticancer drug and nucleic acid delivery.

This critical review covers the developments in anion recognition and sensing using Zn(II)–dipicolylamine functionalized receptors over the past decade with emphasis on recent rapid advances in the last five years.

Anion recognition and sensing with Zn(II)-dipicolylamine complexes.

Advances in bioinformatics, genomics, proteomics, and metabolomics have facilitated the development of novel anticancer agents that have decreased side effects and increased safety. Theranostics, systems that have combined therapeutic effects and diagnostic capabilities, have garnered increasing attention recently because of their potential use in personalized medicine, including cancer-targeting treatments for patients. One interesting approach to achieving this potential involves the development of cancer-associated, stimuli-driven, turn on theranostics. Multicomponent constructs of this type would have the capability of selectively delivering therapeutic reagents into cancer cells or tumor tissues while simultaneously generating unique signals that can be readily monitored under both in vitro and in vivo conditions. Specifically, their combined anticancer activities and selective visual signal respond to cancer-associated stimuli, would make these theranostic agents more highly efficient and specific for cancer treatment and diagnosis. This article focuses on the progress of stimuli-responsive turn on theranostics that activate diagnostic signals and release therapeutic reagents in response to the cancer-associated stimuli. The present article not only provides the fundamental backgrounds of diagnostic and therapeutic tools that have been widely utilized for developing theranostic agents, but also discusses the current approaches for developing stimuli-responsive turn on theranostics.

Cancer-Associated, Stimuli-Driven, Turn on Theranostics for Multimodality Imaging and Therapy.

The most notable role of small interfering RNA (siRNA) is in RNA interference (RNAi) and post-transcriptional gene silencing, which leads to a surge of interest in RNAi for both biomedical research and therapeutic applications. However, “naked” siRNA cannot cross cellular membranes freely because of highly negative charges which limits its utility for gene therapy. In this work, a system of near-infrared (NIR) light-induced siRNA release from silica coated upconversion nanoparticles (Si-UCNPs) is presented. These Si-UCNPs were functionalized with cationic photocaged linkers through covalent bonding, which could effectively adsorb anionic siRNA through electrostatic attractions and were easily internalized by living cells. Upon NIR light irradiation, the photocaged linker on the Si-UCNPs surface could be cleaved by the upconverted UV light and thus initiated the intracellular release of the siRNA. The in vitro agarose gel electrophoresis and intracellular imaging results indicated that the Si-UCNPs-based gene carrier system allowed effective siRNA delivery and the applications of NIR light instead of direct high energy UV irradiation may greatly guarantee less cell damage.

NIR light controlled photorelease of siRNA and its targeted intracellular delivery based on upconversion nanoparticles

In this paper, we present a facile strategy to synthesize hyaluronic acid (HA) conjugated mesoporous silica nanoparticles (MSP) for targeted enzyme responsive drug delivery, in which the anchored HA polysaccharides not only act as capping agents but also as targeting ligands without the need of additional modification. The nanoconjugates possess many attractive features including chemical simplicity, high colloidal stability, good biocompatibility, cell-targeting ability, and precise cargo release, making them promising agents for biomedical applications. As a proof-of-concept demonstration, the nanoconjugates are shown to release cargoes from the interior pores of MSPs upon HA degradation in response to hyaluronidase-1 (Hyal-1). Moreover, after receptor-mediated endocytosis into cancer cells, the anchored HA was degraded into small fragments, facilitating the release of drugs to kill the cancer cells. Overall, we envision that this system might open the door to a new generation of carrier system for site-selective, controlled-release delivery of anticancer drugs.

Bioresponsive Hyaluronic Acid‐Capped Mesoporous Silica Nanoparticles for Targeted Drug Delivery

Small interfering RNA (siRNA) has specific and effective gene silencing effects and has rapidly emerged as a potent strategy for cancer therapy[1] Naked siRNA cannot readily cross cellular membranes, and the delivery of siRNA to its target remains the biggest hurdle to clinical translation[2] Various types of synthetic nanovectors have been investigated for siRNA delivery[3] Although many promising systems for the delivery of siRNA have been reported, clinical translation of siRNA therapeutics remains a challenge Herein, we report a nanoparticle-based system for delivering siRNA into cells that uses a biodegradable conjugate with a high cell permeability for targeting tumors, and a universal phosphate-binding analogue for high siRNA binding affinity

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Sticky Nanoparticles: A Platform for siRNA Delivery by a Bis(zinc(II) dipicolylamine)‐Functionalized, Self‐Assembled Nanoconjugate

The mutation of C-24 reductase, a key enzyme involved in brassinolide biosynthesis, confers a novel compact plant architecture phenotype to cucumber

Back Cover: Sticky Nanoparticles: A Platform for siRNA Delivery by a Bis(zinc(II) dipicolylamine)‐Functionalized, Self‐Assembled Nanoconjugate (Angew. Chem. Int. Ed. 2/2012)

Juan Yin

Papers

Sticky Nanoparticles: A Platform for siRNA Delivery by a Bis(zinc(II) dipicolylamine)‐Functionalized, Self‐Assembled Nanoconjugate

The mutation of C-24 reductase, a key enzyme involved in brassinolide biosynthesis, confers a novel compact plant architecture phenotype to cucumber

Back Cover: Sticky Nanoparticles: A Platform for siRNA Delivery by a Bis(zinc(II) dipicolylamine)‐Functionalized, Self‐Assembled Nanoconjugate (Angew. Chem. Int. Ed. 2/2012)