Publications (7)22.43 Total impact
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Article: Positively Charged Dendron Micelles Display Negligible Cellular Interactions.
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ABSTRACT: PEGylated dendron-based copolymers (PDC) with different end-group functionalities (-NH(2), -COOH, and -Ac) were synthesized and self-assembled into dendron micelles to investigate the effect of terminal surface charges on size, morphology, and cellular interactions of the micelles. All of the dendron micelles exhibited similar sizes (20-60 nm) and spherical morphologies, as measured using dynamic light scattering and transmission electron microscopy, respectively. The cellular interactions of dendron micelles were evaluated using confocal microscopy and flow cytometry. Surprisingly, although amine-terminated dendrimers are known to strongly interact with cells non-specifically, all of the surface-modified dendron micelles exhibited charge-independent low-levels of cellular interaction. The unexpected results, particularly from the amine-terminated dendron micelles, could be attributed to: i) minimal end-group effects, as each PDC has an approximately 10-fold lower charge-number-to-molecular-weight ratio compared to the dendrimer; and ii) intra- and intermolecular hydrogen bonding between positively charged terminal groups with poly(ethylene glycol) (PEG) backbones, which leads to the sequestration of the charges, as demonstrated by atomistic molecular dynamics simulations. With the narrow size distribution, uniform morphologies, and low levels of non-specific cellular interactions, the dendron micelles offer a promising drug delivery platform.ACS macro letters. 01/2013; 2(1):77-81. -
Article: Dendritic nanoparticles: the next generation of nanocarriers?
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ABSTRACT: Dendritic polymers have attracted a great deal of scientific interest due to their well-defined unique structure and capability to be multifunctionalized. Here we present a comprehensive overview of various dendrimer-based nanomaterials that are currently being investigated for therapeutic delivery and diagnostic applications. Through a critical review of the old and new dendritic designs, we highlight the advantages and disadvantages of these systems and their structure-biological property relationships. This article also focuses on the major challenges facing the clinical translation of these nanomaterials and how these challenges are being (or should be) addressed, which will greatly benefit the overall progress of dendritic materials for theranostics.Therapeutic delivery 08/2012; 3(8):941-59. -
Article: Temporal control over cellular targeting through hybridization of folate-targeted dendrimers and PEG-PLA nanoparticles.
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ABSTRACT: Polymeric nanoparticles (NPs) and dendrimers are two major classes of nanomaterials that have demonstrated great potential for targeted drug delivery. However, their targeting efficacy has not yet met clinical needs, largely because of a lack of control over their targeting kinetics, which often results in rapid clearance and off-target drug delivery. To address this issue, we have designed a novel hybrid NP (nanohybrid) platform that allows targeting kinetics to be effectively controlled through hybridization of targeted dendrimers with polymeric NPs. Folate (FA)-targeted generation 4 poly(amidoamine) dendrimers were encapsulated into poly(ethylene glycol)-b-poly(D,L-lactide) (PEG-PLA) NPs using a double emulsion method, forming nanohybrids with a uniform size (~100 nm in diameter) at high encapsulation efficiencies (69-85%). Targeted dendrimers encapsulated within the NPs selectively interacted with FA receptor (FR)-overexpressing KB cells upon release in a temporally controlled manner. The targeting kinetics of the nanohybrids were modulated using three different molecular weights (MW) of the PLA block (23, 30, and 45 kDa). The release rates of the dendrimers from the nanohybrids were inversely proportional to the MW of the PLA block, which dictated their binding and internalization kinetics with KB cells. Our results provide evidence that selective cellular interactions can be kinetically controlled by the nanohybrid design, which can potentially enhance targeting efficacy of nanocarriers.Biomacromolecules 03/2012; 13(4):1223-30. · 5.48 Impact Factor -
Article: Dendron-mediated self-assembly of highly PEGylated block copolymers: a modular nanocarrier platform.
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ABSTRACT: PEGylated dendron coils (PDCs) were investigated as a novel potential nanocarrier platform. PDCs self-assembled into micelles at lower CMCs than linear copolymer counterparts by 1-2 orders of magnitude, due to the unique architecture of dendrons. MD simulations also supported thermodynamically favourable self-assembly mediated by dendrons.Chemical Communications 08/2011; 47(37):10302-4. · 6.17 Impact Factor -
Article: Facilitated self-assembly of novel dendron-based copolymers.
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ABSTRACT: Self-assembly of newly synthesized dendron-based amphiphilic copolymers with controlled hydrophilic-lipophilic balances has been investigated to evaluate their potential as a novel nanocarrier. The hydroxyl-terminated polyester dendron (G3) bearing a focal alkyne moiety was used to mediate the combination of poly(s-caprolactone) (PCL) with multiple polyethylene glycol (PEG) moieties. Four types of PCL-G3-mPEG with different block lengths were prepared and their structures were confirmed by (1)H NMR, FT-IR, and GPC. Critical micelle concentration (CMC) values varied from 6.50 × 10(-8) to 3.52 × 10(-7) M, which were lower than those reported for linear PCL-mPEG. TEM revealed that all PCL-G3-mPEG micelles were spherical with an average diameter of 20 nm. The drug release profile for each PCL-G3-mPEG was investigated by loading indomethacin (IMC), as a model drug, within the micelles. IMC was released in a controlled manner over 72 hours. Synthesized copolymers used in this study were also found to be non-cytotoxic at concentrations up to 100 μM. The low CMC, along with the controlled morphology, release profile and biocompatibility, all demonstrate the potential of the dendron-based micelles as a novel nanocarrier.Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 08/2011; 2011:8334-6. -
Article: Kinetically controlled cellular interactions of polymer-polymer and polymer-liposome nanohybrid systems.
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ABSTRACT: Although bioactive polymers such as cationic polymers have demonstrated potential as drug carriers and nonviral gene delivery vectors, high toxicity and uncontrolled, instantaneous cellular interactions of those vectors have hindered the successful implementation In Vivo. Fine control over the cellular interactions of a potential drug/gene delivery vector would be thus desirable. Herein, we have designed nanohybrid systems (100-150 nm in diameter) that combine the polycations with protective outer layers consisting of biodegradable polymeric nanoparticles (NPs) or liposomes. A commonly used polycation polyethylenimine (PEI) was employed after conjugation with rhodamine (RITC). The PEI-RITC conjugates were then encapsulated into (i) polymeric NPs made of either poly(lactide-co-glycolide) (PLGA) or poly(ethylene glycol)-b-poly(lactide-co-glycolide) (PEG-PLGA); or (ii) PEGylated liposomes, resulting in three nanohybrid systems. Through the nanohybridization, both cellular uptake and cytotoxicity of the nanohybrids were kinetically controlled. The cytotoxicity assay using MCF-7 cells revealed that liposome-based nanohybrids exhibited the least toxicity, followed by PEG-PLGA- and PLGA-based NPs after 24 h incubation. The different kinetics of cellular uptake was also observed, the liposome-based systems being the fastest and PLGA-based systems being the slowest. The results present a potential delivery platform with enhanced control over its biological interaction kinetics and passive targeting capability through size control.Bioconjugate Chemistry 02/2011; 22(3):466-74. · 4.93 Impact Factor -
Article: Direct measurements on CD24-mediated rolling of human breast cancer MCF-7 cells on E-selectin.
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ABSTRACT: Tumor cell rolling on the endothelium plays a key role in the initial steps of cancer metastasis, i.e., extravasation of circulating tumor cells (CTCs). Identification of the ligands that induce the rolling of cells is thus critical to understanding how cancers metastasize. We have previously demonstrated that MCF-7 cells, human breast cancer cells, exhibit the rolling response selectively on E-selectin-immobilized surfaces. However, the ligand that induces rolling of MCF-7 cells on E-selectin has not yet been identified, as these cells lack commonly known E-selectin ligands. Here we report, for the first time to our knowledge, a set of quantitative and direct evidence demonstrating that CD24 expressed on MCF-7 cell membranes is responsible for rolling of the cells on E-selectin. The binding kinetics between CD24 and E-selectin was directly measured using surface plasmon resonance (SPR), which revealed that CD24 has a binding affinity against E-selectin (K(D) = 3.4 ± 0.7 nM). The involvement of CD24 in MCF-7 cell rolling was confirmed by the rolling behavior that was completely blocked when cells were treated with anti-CD24. A simulated study by flowing microspheres coated with CD24 onto E-selectin-immobilized surfaces further revealed that the binding is Ca(2+)-dependent. Additionally, we have found that actin filaments are involved in the CD24-mediated cell rolling, as observed by the decreased rolling velocities of the MCF-7 cells upon treatment with cytochalasin D (an inhibitor of actin-filament dynamics) and the stationary binding of CD24-coated microspheres (the lack of actins) on the E-selectin-immobilized slides. Given that CD24 is known to be directly related to enhanced invasiveness of cancer cells, our results imply that CD24-based cell rolling on E-selectin mediates, at least partially, cancer cell extravasation, resulting in metastasis.Analytical Chemistry 01/2011; 83(3):1078-83. · 5.86 Impact Factor
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Institutions
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2011–2013
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University of Illinois at Chicago
- Department of Biopharmaceutical Sciences
Chicago, IL, USA
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