Magnetic nanoparticle formulations for DNA and siRNA delivery

Mykhaylyk, Olga; Vlaskou, Dialekti; Tresilwised, Nittaya; Pithayanukul, Pimolpan; Möller, Winfrid; Plank, Christian

doi:10.1016/j.jmmm.2006.10.1178

Cited by 73 publications

(43 citation statements)

References 22 publications

(18 reference statements)

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“…PEI-Mag2 and SO-Mag2 magnetic nanoparticles were synthesized as previously described 29,30 (supplemental Data; supplemental Table 1, available on the Blood Web site; see the Supplemental Materials link at the top of the online article). The particle stock concentration in terms of iron content was determined as described previously.…”

Section: Magnetic Lipoplexesmentioning

confidence: 99%

Magselectofection: an integrated method of nanomagnetic separation and genetic modification of target cells

Sanchez-Antequera

Mykhaylyk

Til

et al. 2011

Blood

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Research applications and cell therapies involving genetically modified cells require reliable, standardized, and costeffective methods for cell manipulation. We report a novel nanomagnetic method for integrated cell separation and gene delivery. Gene vectors associated with magnetic nanoparticles are used to transfect/transduce target cells while being passaged and separated through a high gradient magnetic field cell separation column. The integrated method yields excellent target cell purity and recovery. Nonviral and lentiviral magselectofection is efficient and highly specific for the target cell population as demonstrated with a K562/Jurkat T-cell mixture. Both mouse and human enriched hematopoietic stem cell pools were effectively transduced by lentiviral magselectofection, which did not affect the hematopoietic progenitor cell number determined by in vitro colony assays. Highly effective reconstitution of T and B lymphocytes was achieved by magselectofected murine wild-type lineage-negative Sca-1 ؉ cells transplanted into Il2rg ؊/؊ mice, stably expressing GFP in erythroid, myeloid, T-, and B-cell lineages. Furthermore, nonviral, lentiviral, and adenoviral magselectofection yielded high transfection/ transduction efficiency in human umbilical cord mesenchymal stem cells and was fully compatible with their differentiation potential. Upscaling to a clinically approved automated cell separation device was feasible. Hence, once optimized, validated, and approved, the method may greatly facilitate the generation of genetically engineered cells for cell therapies. (Blood. 2011;117(16): e171-e181) IntroductionThe feasibility of using genetically engineered cells for therapy in humans has been demonstrated using various cell types, including tumor cells, 1-3 lymphocytes, dendritic cells, 4,5 fibroblasts, 6,7 hematopoietic stem cells (HSCs), 8,9 and mesenchymal stem cells (MSCs). 10,11 Actual or potential applications are as diverse as immune gene therapy for the treatment of cancer, 1-3 cancer therapy with T cells expressing chimeric T-cell receptors, 12,13 the treatment of hereditary diseases, 8,9,[14][15][16] and a plethora of applications in regenerative medicine. 17 With the emerging field of induced pluripotent stem cells, research in genetically engineered cell therapies has reached yet another level of pace and dimension. Clinical applications will require efficient, reliable, standardized methods for cell manipulation. For optimized reproducibility and wide practicality in a decentralized manner, such methods should compose a minimum number of handling steps and be cost-effective and amenable to automation in a closed system.The goal of this work is to provide a novel methodology for performing genetic modification and cell isolation in a single standardized procedure, which we call "magselectofection" ( Figure 1). It integrates nanomagnetic cell separation, which is an approved clinical application, 18,19 and nanomagnetically guided nucleic acid delivery known as magnetofection. [20][21][22] For magneti...

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Section: Magnetic Lipoplexesmentioning

confidence: 99%

Magselectofection: an integrated method of nanomagnetic separation and genetic modification of target cells

Sanchez-Antequera

Mykhaylyk

Til

et al. 2011

Blood

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“…In fact, both in vitro and in vivo studies demonstrated that microspheremediated delivery of rAAV vector results in higher transduction efficiencies than delivery of free vector alone, when administered either intramuscularly or intravenously (Mah et al 2002). Currently, in vitro magnetofection kits utilizing cationic polymer coated MNPs are commercially available (Mykhaylyk et al 2007;Pan et al 2007;Ryther et al 2005;Schillinger et al 2005). Huth et al showed that the cationic polymeric gene carriers, such as polyethylenimine (PEI) increase the cellular uptake of magnetofectins (Huth et al 2004).…”

Section: Magnetic Nanoparticles For Gene Deliverymentioning

confidence: 99%

Magnetic nanoparticle drug delivery systems for targeting tumor

et al. 2013

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Tumor hypoxia, or low oxygen concentration, is a result of disordered vasculature that lead to distinctive hypoxic microenvironments not found in normal tissues. Many traditional anti-cancer agents are not able to penetrate into these hypoxic zones, whereas, conventional cancer therapies that work by blocking cell division are not effective to treat tumors within hypoxic zones. Under these circumstances the use of magnetic nanoparticles as a drug delivering agent system under the influence of external magnetic field has received much attention, based on their simplicity, ease of preparation, and ability to tailor their properties for specific biological applications. Hence in this review article we have reviewed current magnetic drug delivery systems, along with their application and clinical status in the field of magnetic drug delivery.

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“…PEI has been described using different kinds of nanoparticles directly adsorbed on negatively charged materials [74,92] or covalently attached by amination [93]. There are many examples of the functionalization of AuNPs [94,95], MNPs [54,[96][97][98], SiNPs [61,99,100], with PEI of different molecular weights [61,101] or even modified with labile bonds like acetal [102]. In relation to the PLL, this polymer has been used previously modified with a terminal cysteine for the direct attachment to AuNPs [103], conjugated to epoxysilanes [62] and as part of a layer-by-layer system with siRNA [104].…”

Section: Ionic Approachmentioning

confidence: 99%

15 years on siRNA delivery: Beyond the State-of-the-Art on inorganic nanoparticles for RNAi therapeutics

et al. 2015

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RNAi has always captivated scientists due to its tremendous power to modulate the phenotype of living organisms. This natural and powerful biological mechanism can now be harnessed to downregulate specific gene expression in diseased cells; opening up endless opportunities. Since most of the conventional siRNA delivery methods are limited by a narrow therapeutic index and significant side and off-target effects, we are now in the dawn of a new age in gene therapy driven by nanotechnology vehicles for RNAi therapeutics. Here, we outlook the "do's and dont's" of the 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 REVIEW NANO TODAY 2 inorganic RNAi nanomaterials developed in the last 15 years and the different strategies employed are compared and scrutinized, offering important suggestions for the next 15. *Manuscript Click here to view linked References

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Magnetic nanoparticle formulations for DNA and siRNA delivery

Cited by 73 publications

References 22 publications

Magselectofection: an integrated method of nanomagnetic separation and genetic modification of target cells

Magselectofection: an integrated method of nanomagnetic separation and genetic modification of target cells

Magnetic nanoparticle drug delivery systems for targeting tumor

15 years on siRNA delivery: Beyond the State-of-the-Art on inorganic nanoparticles for RNAi therapeutics

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