Chemical and Biomolecular Engineering - Research Publications
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ItemNo Preview AvailableImmobilization and Intracellular Delivery of an Anticancer Drug Using Mussel-Inspired Polydopamine Capsules(AMER CHEMICAL SOC, 2012-08)We report a facile approach to immobilize pH-cleavable polymer-drug conjugates in mussel-inspired polydopamine (PDA) capsules for intracellular drug delivery. Our design takes advantage of the facile PDA coating to form capsules, the chemical reactivity of PDA films, and the acid-labile groups in polymer side chains for sustained pH-induced drug release. The anticancer drug doxorubicin (Dox) was conjugated to thiolated poly(methacrylic acid) (PMA(SH)) with a pH-cleavable hydrazone bond, and then immobilized in PDA capsules via robust thiol-catechol reactions between the polymer-drug conjugate and capsule walls. The loaded Dox showed limited release at physiological pH but significant release (over 85%) at endosomal/lysosomal pH. Cell viability assays showed that Dox-loaded PDA capsules enhanced the efficacy of eradicating HeLa cancer cells compared with free drug under the same assay conditions. The reported method provides a new platform for the application of stimuli-responsive PDA capsules as drug delivery systems.
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ItemThe Role of Particle Geometry and Mechanics in the Biological Domain(WILEY, 2012-01-11)Nanostructured particulate materials are expected to revolutionize diagnostics and the delivery of therapeutics for healthcare. To date, chemistry-derived solutions have been the major focus in the design of materials to control interactions with biological systems. Only recently has control over a new set of physical parameters, including size, shape, and rigidity, been explored to optimize the biological response and the in vivo performance of nanoengineered delivery vectors. This Review highlights the methods used to manipulate the physical properties of particles and the relevance of these physical properties to cellular and circulatory interactions. Finally, the importance of future work to synergistically tailor both physical and chemical properties of particulate materials is discussed, with the aim of improving control over particle interactions in the biological domain.
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ItemTemplated Assembly of pH-Labile Polymer-Drug Particles for Intracellular Drug Delivery(WILEY-V C H VERLAG GMBH, 2012-11-21)Abstract The preparation of pH‐labile polymer‐drug particles via mesoporous silica‐templated assembly for anticancer drug delivery into cancer cells is reported. The polymer‐drug conjugate is synthesized via thiol‐maleimide click chemistry using thiolated poly(methacrylic acid) (PMASH) and a pH‐labile doxorubicin (Dox) derivative. Drug‐loaded polymer particles that are stable under physiological conditions are obtained through infiltration of the conjugates into mesoporous silica particles, followed by cross‐linking the PMASH chains, and subsequent removal of the porous silica templates. The encapsulated Dox is released from the particles through cleavage of the hydrazone bonds between Dox and PMASH at endosomal/lysosomal pH. Cell viability assays show that the assembled PMASH particles have negligible cytotoxicity to LIM1899 human colorectal cancer cells. In comparison, Dox‐loaded PMASH particles cause significant cell death following internalization. The reported particles represent a novel and versatile class of stimuli‐responsive carriers for controlled drug delivery.
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ItemMacromolecule Functionalization of Disulfide-Bonded Polymer Hydrogel Capsules and Cancer Cell Targeting(AMER CHEMICAL SOC, 2012-02)We present a generic and versatile method for functionalization of disulfide-stabilized PMA hydrogel capsules (HCs) with macromolecules, including a number of specific antibodies to cancer cells. Functionalization was achieved by reversible addition-fragmentation chain transfer (RAFT) polymerization of poly(N-vinyl pyrrolidone) (PVPON), which introduced biorelevant heterotelechelic end groups (thiol and amine) to the polymer chain. The PVPON with heterotelechelic end groups was conjugated to the outermost layer of PMA HCs through the thiol groups and reacted with biotin via the amine groups to generate PMA/PVPON(biotin) HCs. On the basis of the high specific interaction and high affinity between biotin and avidin, and its derivates, such as NeutrAvidin (NAv), we functionalized the PMA HCs with biotinylated antibodies. We demonstrate significantly enhanced cellular binding and internalization of the antibody (Ab)-functionalized capsules compared with control human immunoglobulin (IgG)-functionalized capsules, suggesting these capsules can specifically interact with cells through antibody/antigen recognition. We anticipate that the versatility of the functionalization approach reported in this study will assist in targeted therapeutic delivery applications.
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ItemEngineering Particles for Therapeutic Delivery: Prospects and Challenges(AMER CHEMICAL SOC, 2012-05)Nanoengineered particles that can facilitate drug formulation and passively target tumors have reached the clinic in recent years. These early successes have driven a new wave of significant innovation in the generation of advanced particles. Recent developments in enabling technologies and chemistries have led to control over key particle properties, including surface functionality, size, shape, and rigidity. Combining these advances with the rapid developments in the discovery of many disease-related characteristics now offers new opportunities for improving particle specificity for targeted therapy. In this Perspective, we summarize recent progress in particle-based therapeutic delivery and discuss important concepts in particle design and biological barriers for developing the next generation of particles.
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ItemEmerging Techniques in Proteomics for Probing Nano-Bio Interactions(AMER CHEMICAL SOC, 2012-12)Nanoengineered particles that can facilitate drug formulation and improve specificity of delivery afford exciting opportunities for improved lesion-specific therapy. Understanding and controlling the nano-bio interactions of these materials is central to future developments in this area. Mass-spectrometry-based proteomics techniques, in conjunction with other emerging technologies, are enabling novel insights into the modulation of particle surfaces by biological fluids (formation of the protein corona) and subsequent particle-induced cellular responses. In this Perspective, we summarize important recent developments using proteomics-based techniques to understand nano-bio interactions and discuss the impact of such knowledge on improving particle design.