Hyaluronan grafted lipid-based nanoparticles as RNAi carriers for cancer cells

Landesman-Milo, Dalit; Goldsmith, Meir; Ben-Arye, Shani Leviatan; Witenberg, Bruria; Brown, Emile N.; Leibovitch, Sigalit; Azriel, Shalhevet; Tabak, Sarit; Morad, Vered; Peer, Dan

doi:10.1016/j.canlet.2012.08.024

Cited by 64 publications

(38 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(29)(30)(31)(32) The strong interactions between the negative phosphate groups on nucleotides and the positive charges of amino groups on cationic lipids lead to such a high association efficiency. (33)(34)(35) However, this binding decreased to 60-70% at a ± ratio of 1, indicating a possible saturation of the available positively charged binding sites on the liposomes occurring between ± ratios of 1 and 2 (Figure 3 A). Lipoplexes at ± ratio 2 (negative zeta potential) were chosen for further experiments while in some cases and to understand lipoplex formation higher ± ratios were used (positively charged close to the initial liposome characteristics).…”

Section: Resultsmentioning

confidence: 98%

Supramolecular Organization and siRNA Binding of Hyaluronic Acid-Coated Lipoplexes for Targeted Delivery to the CD44 Receptor

et al. 2015

View full text Add to dashboard Cite

Original Citation:Supramolecular organization and siRNA binding of hyaluronic acid-coated lipoplexes for targeted delivery to the CD44 receptor. Published version:DOI:10.1021/acs.langmuir.5b01979 Terms of use:Open Access (Article begins on next page) Anyone can freely access the full text of works made available as "Open Access". Works made available under a Creative Commons license can be used according to the terms and conditions of said license. Use of all other works requires consent of the right holder (author or publisher) if not exempted from copyright protection by the applicable law. Availability: This is the author's manuscript AbstractThe dynamics of the formation of siRNA-lipoplexes coated with hyaluronic acid (HA) and the parameters influencing their supramolecular organization were studied. The insertion of a HAdioleylphosphatidylethanolamine (DOPE) conjugate in the liposome structure as well as subsequent complexation with siRNA increased the liposome size. Lipoplexes were around 110 nm at high ± charge ratios with a zeta potential around +50 mV and around 230 nm at low ± ratios, with a zeta potential that decreased to negative values, reaching −45 mV. The addition of the conjugate did not compromise siRNA binding to liposomes, although these nucleic acids induced a displacement of part of the HA-DOPE conjugate upon lipoplex formation, as confirmed by capillary electrophoresis. Isothermal titration calorimetry, X-ray diffraction studies, and cryo-TEM microscopy demonstrated that in addition to electrostatic interactions with siRNA a rearrangement of the lipid bilayers takes place, resulting in condensed oligolamellar vesicles. This phenomenon is dependent on the number of siRNA molecules and the degree of modification with HA. Finally, the suitable positioning of HA on the lipoplex surface and its ability to bind specifically to the CD44 receptors in a concentrationdependent manner was demonstrated by surface plasmon resonance analysis.

show abstract

Section: Resultsmentioning

confidence: 98%

Supramolecular Organization and siRNA Binding of Hyaluronic Acid-Coated Lipoplexes for Targeted Delivery to the CD44 Receptor

et al. 2015

View full text Add to dashboard Cite

show abstract

“…For encapsulation analysis of Human miRIDIAN miR125a-5p Mimic or scramble miR negative control (both from Dharmacon), a specific RNA binding dye, Quant-iT Ribogreen RNA Assay (Invitrogen), was utilized in the presence and absence of 0.1% Triton X100 detergent following a previous protocol. 48 The RNA binding dye is unable to penetrate intact lipid membranes, and therefore in the absence of detergent only the fluorescence of the un-entrapped miRNA can be measured. But, in the presence of detergent, the total fluorescence can be measured to determine the % encapsulation.…”

Section: Rehydration (Entrapment) Protocol and Cargo Encapsulation Qumentioning

confidence: 99%

Targeted Delivery of MicroRNA125a-5p by Engineered Lipid Nanoparticles for the Treatment of HER2 Positive Metastatic Breast Cancer

Hayward

Francis

Kholmatov

et al. 2016

j biomed nanotechnol

View full text Add to dashboard Cite

MicroRNAs (miRNAs) are endogenous regulators of gene expression that play a pivotal role in biological processes spanning from global homeostasis to disease onset and progression. The ability to manipulate and induce cellular reequilibrium of deregulated miRNA expression profiles by inhibition of oncogenic miRNA or overexpression of tumor suppressor miRNA is a promising cancer strategy, but is currently hindered in application by the lack of nonviral delivery systems. Here we present a lipid nanoparticle (LNP) platform surface coated with Hyaluronic Acid (HA) for the delivery of mature tumor suppressor MicroRNA125a-5p to treat HER2 positive metastatic breast cancer. The delivery platform actively targets patient-derived metastatic breast cancer cells (21MT-1) isolated from the metastatic pleural effusion over normal breast tissue via an intrinsic HA-CD44 mediated endocytosis event, and has the ability to escape from the intracellular endolysosomal pathway for potent gene silencing. Knockdown of the HER2 proto-oncogene at the level of transcription and translation was achieved following HA-LNP mediated transfection with MicroRNA125a-5p. In addition, the PI3K/AKT and MAPK hyperactivated signaling pathways, cellular proliferation, and migration potential were also potently suppressed. Furthermore, the therapeutic efficacy of MicroRNA125a-5p by the HA-LNP platform was demonstrated to be significantly improved as compared to a commercial transfection reagent. This study highlights the therapeutic potential of MicroRNA125a-5p as a standalone treatment of HER2+ metastatic breast cancer via a translational nonviral delivery platform. These findings have major implications on future gene therapy regimens for breast cancer.

show abstract

“…Most gene transfection and drug delivery vectors are constructed from various cationic molecules. Lipid-based schemes are composed of different cationic lipids with helper lipids such as DOTAP used in this study (Landesman et al, 2013). Cationic nanoparticles can potentially overcome such physical barriers because they penetrate into tumor tissues.…”

Section: Discussionmentioning

confidence: 99%

Which one performs better for targeted lung cancer combination therapy: pre- or post-bombesin-decorated nanostructured lipid carriers?

Li²

2015

Drug Delivery

View full text Add to dashboard Cite

Purpose: The co-delivery of gene and drugs has the potential to treat cancer. The aim of this study was to compare post-bombesin decorated nanostructured lipid carriers (NLC) carrying both doxorubicin (DOX) and DNA with pre-bombesin decorated NLC for lung cancer therapy. Methods: Post-bombesin decorated NLC were prepared by two steps. First, DOX and DNA-loaded NLC (DOX-DNA-NLC) was prepared. Second, Bombesin-NH 2 (BN-NH 2 ) was added into DOX-DNA-NLC to react with stearic acid-polyethylene glycol-COOH (SA-PEG-COOH) loaded in NLC. Pre-bombesin decorated NLC were prepared by two steps. First, Bombesin (BN)-conjugated ligands were synthesized. Second, DOX and DNA were loaded into BN decorated NLC. Their average size, zeta potential, drug and gene loading were evaluated. NCl-H460 human non-small lung cancer cells (NCl-H460 cells) were used for the testing of in vitro transfection efficiency and in vitro cytotoxicity. In vivo transfection efficiency and anti-tumor effect of NLC were evaluated on mice bearing NCl-H460 cells model. Results: Post-bombesin decorated NLC has a particle size of 128 nm, DOX encapsulation efficiency (EE) of 85% and DNA EE of 91%. Pre-bombesin decorated NLC has a particle size of 101 nm, DOX EE of 86% and DNA EE of 92%. Post-bombesin decorated NLC displayed more stable and remarkably higher transfection efficiency and better anti-tumor ability than pre-bombesin decorated NLC both in vitro and in vivo. Conclusion: Post-bombesin decorated NLC could function as better carriers to improve the cell targeting and nuclear targeting ability. The resulting nanomedicine could be a promising active targeting drug/gene therapeutic system for lung cancer therapy.

show abstract

Hyaluronan grafted lipid-based nanoparticles as RNAi carriers for cancer cells

Cited by 64 publications

References 35 publications

Supramolecular Organization and siRNA Binding of Hyaluronic Acid-Coated Lipoplexes for Targeted Delivery to the CD44 Receptor

Supramolecular Organization and siRNA Binding of Hyaluronic Acid-Coated Lipoplexes for Targeted Delivery to the CD44 Receptor

Targeted Delivery of MicroRNA125a-5p by Engineered Lipid Nanoparticles for the Treatment of HER2 Positive Metastatic Breast Cancer

Which one performs better for targeted lung cancer combination therapy: pre- or post-bombesin-decorated nanostructured lipid carriers?

Contact Info

Product

Resources

About