Leaf Huang

..Rational designs that address safety concerns and ensure effective delivery will aid the translation of engineered lipid-based nanoparticles toward the clinic in the foreseeable future...

..The activity and the toxicity of LPD- and LPD-II-mediated therapy are compared...

..The untargeted NP showed a very low silencing effect. The new formulation improved the in vitro silencing effect 3-4 folds compared to the previous LPD formulation, but had a negligible immunotoxicity...

..Our data elucidated an important mechanism of adjuvant activity of cationic liposome and could facilitate rational design of synthetic lipid based adjuvants and vaccine formulation...

..In addition, MPS-cytC-NP treatment provoked a tumor growth retardation effect in H460 xenograft mice. We conclude that our NP enables targeted, efficacious therapeutic protein delivery for the treatment of lung cancer...

..The new nanomedicine formulations show clear potential for clinical development because of the excellent antitumor activity, low toxicity, and the ease of scale-up manufacture. The formulation method may apply to other hydrophobic drugs...

..15-1.2 mg siRNA/kg), while the previously published formulation, LPD-NP (liposome-protamine-DNA nanoparticle), had a much narrow therapeutic window (0.15-0.45 mg/kg)...

..At the therapeutic dose, the targeted NP showed little local and systemic immunotoxicity and did not decrease the body weight or damage the major organs...

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..Thus, the targeted nanoparticles containing c-Myc siRNA may serve as an effective therapeutic agent for melanoma...

..We envision that further development of this type of nanocrystal will provide a novel strategy for drug delivery and multidrug resistance treatment...

..Moreover, this targeted LCP NP significantly prolonged the mean survival time of the animals by 27.8% compared to control group without showing any toxicity at the therapeutic dose...

..The tumor appeared to be the major uptake organ for siRNA formulated in surface-modified LPD. Our encouraging results indicate that surface-modified LPD may be a potent carrier for RNAi-based tumor therapy...

..When doxorubicin (DOX) and siRNA were co-formulated in LPD-PEG-NGR, an enhanced therapeutic effect was observed...

..Thus, DSGLA served as both a formulation component as well as a therapeutic agent which synergistically enhanced the activity of siRNA...

..The serum level of liver enzymes and body weight monitoring during the treatment indicated a low level of toxicity of the formulation. The carrier itself also showed little immunotoxicity (IMT)...

..These results suggest that a combination of protein content and DNA placement within the structure is responsible for the significantly improved efficacy and decreased inflammatory toxicity of these modified non-viral vectors...

..Overall, the improved DOTAP/E7-lipopeptide vaccine described herein showed a significantly enhanced therapeutic effect for the treatment of a cervical cancer model...

..Bio-distribution study showed that LCP-II required more PEGylation for MPS evasion than the previous LPD, probably due to increased surface curvature in LCP-II...

..Our findings offer proof-of-concept for an intracellular peptide-mediated cancer therapy that is delivered by carefully designed nanoparticles...

..When miR-34a and siRNAs were co-formulated in GC4-targeted nanoparticles, an enhanced anticancer effect was observed...

..This review summarizes different signaling pathways inhibited by siRNA and the advantages of targeted siRNA as a delivery system...

..It resulted in 70-80% gene silencing in the metastasis model after a single i.v. injection (150 microg siRNA/kg). This effective formulation also showed very little immunotoxicity...

..We also underscore the value of sustained release of a nucleic acid in this endeavor; making vectors targeted to cells with sustained release in vivo should provide an interesting research challenge...

..The SDBPs with dysopsonin properties and DNA complexes may be further modified and ultimately be developed into a novel DNA carrier system favorable for systemic gene delivery...

..Furthermore, we have demonstrated that a higher heating temperature (45 degrees C vs. 37 degrees C) used in the incubation-sonication procedure was able to provide even better nanocrystal stability for long periods of incubation time...

..At the end, we discuss different strategies to overcome these barriers, especially focusing on the step of endosome escape. Toxicity issues and current successful examples for lipid-based delivery are also included in the review...

..Thus, (R)-DOTAP has shown the ability to break tolerance as an adjuvant. Its activity to enhance immunogenicity of other tumor associated antigens should be studied further...

..At the end, we show that multifunctional self-assembled lipid-based nanoparticles could also be versatile delivery vehicles for cancer molecular imaging probes...

..Overall, these results indicate that cationic lipid DOTAP alone serves as an efficient vaccine adjuvant for the induction of a therapeutic, antigen-specific anti-cancer activity...

..Naked DNA after intravenous (i.v.) injection will be taken up by the liver and depredated by serum nucleases...

..We also reprise several recent studies that have examined the inter-relationship of size and shape in influencing delivery...

..We hope that our findings would highlight certain issues to be aware of when conducting PK and biodistribution studies for nano-drug carriers...

..Our data elucidated one important mechanism of adjuvant activity of cationic liposome and could facilitate rational design of synthetic lipid based adjuvants...

..The results show the DOTAP enantiomers act differently as adjuvants in vivo, with (R)-DOTAP being more effective at stimulating a CD8(+) anti-tumor response...

..Significant biological effects were attained in the sub-100 nM concentration range...

..We see gene therapy as the most innovative and flexible method to lead the charge to specifically modifying the tumor microenvironment...

..In conclusion, for the first time, we demonstrated that Bryo-I induced chemokine release from dendritic cell and was an effective adjuvant for peptide cancer vaccine...

..This review will discuss the relationships between the tumor and the immune system, and also will include topics covering the strategies used in eliminating tumors by using nanomedicine...

..In this study, we have designed a device and experiments to test the hypothesis...

..Our findings demonstrate in vivo anti-tumor activity of SSOs that modulate Bcl-x pre-mRNA splicing...

..The biodistribution of Lipid/Calcium/Phosphate (LCP) nanoparticles (NPs) in tumor-bearing mice was investigated using fluorescence imaging. A quantitative validation of this method was done by (3)H and (111)In labeling of the nanoparticles...

..Overall, these examples provide hope that free ligand can be used to effectively mediate cellular processes to overcome some of the obstacles limiting the success of gene therapy...

..We will also introduce the current progress in the design of nonviral vectors, and briefly discuss their safety issues...

..Our results suggest that the ligand targeted and sterically stabilized nanoparticles can provide a selective delivery of AS-ODN and siRNA into lung cancer cells for therapy...

..Project will study the activity and the mechanism of the lipid adjuvant, in order to find more active lipid and more efficacious vaccine. ..

..A self-assembled nanoparticle formulation will be used as a delivery vehicle. The project uses lung cancer and lung metastasis in mice as the disease model. ..

..The other is to transport siRNA to tumors with not-so-leaky vasculature. If successful, the project will significantly advance siRNA as cancer therapeutics. ..