Synthesis and characterization of transferrin-targeted chemotherapeutic delivery systems prepared via RAFT copolymerization of high molecular weight PEG macromonomers.

Reversible addition-fragmentation chain transfer (RAFT) polymerization was employed to prepare a nanoparticulate drug delivery system for chemotherapeutics. The nanoparticles contain a PEG "stealth" corona as well as reactive anhydride functionality designed for conjugating targeting proteins. The multifunctional carrier functionality was achieved by controlling the copolymerization of the hydrophobic monomer lauryl methacrylate (LMA), with a reactive anhydride functional methacrylate (TMA), and a large polyethyleneglycol methacrylate monomer (M~950 Da) (O950).

In vivo targeting of alveolar macrophages via RAFT-based glycopolymers.

Targeting cell populations via endogenous carbohydrate receptors is an appealing approach for drug delivery. However, to be effective, this strategy requires the production of high affinity carbohydrate ligands capable of engaging with specific cell-surface lectins. To develop materials that exhibit high affinity towards these receptors, we synthesized glycopolymers displaying pendent carbohydrate moieties from carbohydrate-functionalized monomer precursors via reversible addition-fragmentation chain transfer (RAFT) polymerization.

Efficient gene silencing in lungs and liver using imidazole-modified chitosan as a nanocarrier for small interfering RNA.

Despite high specificity and potency, small interfering RNA (siRNA)-based therapeutics have been limited by their poor biostability and intracellular penetration. Thus, effective nanocarriers that can protect and efficiently deliver siRNA to target cells in vivo are needed. Here we report on the efficiency of imidazole-modified chitosan (chitosan-imidazole-4-acetic acid [IAA])-siRNA nanoparticles to mediate gene silencing after administration via either intravenous (i.

Efficient mucosal delivery of optical contrast agents using imidazole-modified chitosan.

The clinical applicability of antibodies and plasmonic nanosensors as topically applied, molecule-specific optical diagnostic agents for noninvasive early detection of cancer and precancer is severely limited by our inability to efficiently deliver macromolecules and nanoparticles through mucosal tissues. We have developed an imidazole-functionalized conjugate of the polysaccharide chitosan (chitosan-IAA) to enhance topical delivery of contrast agents, ranging from small molecules and antibodies to gold nanoparticles up to 44 nm in average diameter. Contrast agent uptake and localization in freshly resected mucosal tissues was monitored using confocal microscopy.

Efficient modulation of T-cell response by dual-mode, single-carrier delivery of cytokine-targeted siRNA and DNA vaccine to antigen-presenting cells.

Controlled modulation of T-cell response during immunotherapy, especially the balance between T helper 1 (Th1) and Th2 responses, is critical for generating effective immune response. Here we report that dual delivery of interleukin 10 (IL-10)-targeted small interfering RNA (siRNA) and DNA vaccines to dendritic cells (DCs), using a single particle carrier, efficiently enhances immune response and modulates it toward a stronger Th1 phenotype. Surface-functionalized polymer microparticles (MPs) carrying both IL-10-targeted siRNA and DNA antigens exhibited effective gene silencing, DNA transfection, and synergistically enhanced upregulation of maturation markers in primary DCs leading to increased T-cell proliferation, in vitro.

Enhancing polysaccharide-mediated delivery of nucleic acids through functionalization with secondary and tertiary amines.

Chitosan is a polysaccharide that has generated significant interest as a non-viral gene delivery vehicle due to its cationic and biocompatible characteristics. However, transfection efficiency of chitosan is significantly lower compared to other cationic gene delivery agents, e.g.

Encapsulation of nucleic acids and opportunities for cancer treatment.

The development of nucleic acid drugs for the treatment of various cancers has shown great promise in recent years. However, efficient delivery of these drugs to target cells remains a significant challenge towards the successful development of such therapies. This review provides a comprehensive overview of encapsulation technologies being developed for the delivery of nucleic acid-based anti-cancer agents.

Control of DNA hybridization with photocleavable adducts.

Previous reports have shown that 1-(4,5-dimethoxy-2-nitrophenyl)ethyl ester (DMNPE) adducts coupled to DNA plasmids block transcription in vitro and in vivo until removed with light. In this report, we explore the use of DMNPE to control DNA hybridization. We found that DMNPE-caged oligonucleotides have changed spectrophotometric and electrophoretic properties that can be restored with light exposure.