Multimodal Magnetic Core–Shell Nanoparticles for Effective Stem‐Cell Differentiation and Imaging

Shah, Birju P.; Yin, Perry T.; Ghoshal, Shraboni; Lee, Ki‐Bum

doi:10.1002/anie.201302245

Cited by 72 publications

(71 citation statements)

References 44 publications

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“…29−31 Additionally, our group as well as others have recently demonstrated that these MNPs can be further modified with a gold shell, thus having both magnetic and plasmonic properties that can be utilized for various biological applications including cell targeting, imaging, and chemotherapy. 32 …”

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confidence: 99%

Core–Shell Nanoparticle-Based Peptide Therapeutics and Combined Hyperthermia for Enhanced Cancer Cell Apoptosis

et al. 2014

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Mitochondria-targeting peptides have garnered immense interest as potential chemotherapeutics in recent years. However, there is a clear need to develop strategies to overcome the critical limitations of peptides, such as poor solubility and the lack of target specificity, which impede their clinical applications. To this end, we report magnetic core–shell nanoparticle (MCNP)-mediated delivery of a mitochondria-targeting pro-apoptotic amphipathic tail-anchoring peptide (ATAP) to malignant brain and metastatic breast cancer cells. Conjugation of ATAP to the MCNPs significantly enhanced the chemotherapeutic efficacy of ATAP, while the presence of targeting ligands afforded selective delivery to cancer cells. Induction of MCNP-mediated hyperthermia further potentiated the efficacy of ATAP. In summary, a combination of MCNP-mediated ATAP delivery and subsequent hyperthermia resulted in an enhanced effect on mitochondrial dysfunction, thus resulting in increased cancer cell apoptosis.

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confidence: 99%

Core–Shell Nanoparticle-Based Peptide Therapeutics and Combined Hyperthermia for Enhanced Cancer Cell Apoptosis

et al. 2014

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“…These cores have previously been shown to have a significantly higher saturation magnetization when compared to conventional Fe 2 O 3 or Fe 3 O 4 magnetic nanoparticles (MNPs) [25]. As such, we first synthesized ZnFe 2 O 4 cores with a doping percentage of (Zn 0.4 Fe 0.6 )Fe 2 O 4 via the thermal decomposition of a mixture of metal precursors (zinc chloride, ferrous chloride, and ferric acetylacetonate) in the presence of oleic acid and oleylamine using a previously reported protocol that was modified by our group [23, 25]. Following core synthesis, an inert mSi shell was formed via the condensation of TEOS in the presence of a CTAB micelle template [26].…”

Section: Resultsmentioning

confidence: 99%

“…Thereafter, the MCNP complexes were mixed with Opti MEM (Life Technologies) and added to each well to attain the desired final concentration of plasmid/well. Subsequently, the cell culture plates were placed on a static Nd-Fe-B magnetic plate (OZ Biosciences, France) for 10 minutes (as optimized from previous reports) [23]. The culture plates were placed back into the incubator for 5 hrs and afterwards, the cells were washed with DPBS and the transfection medium was replaced with fresh growth medium.…”

Section: Methodsmentioning

confidence: 99%

Stem cell-based gene therapy activated using magnetic hyperthermia to enhance the treatment of cancer

et al. 2016

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Stem cell-based gene therapies, wherein stem cells are genetically engineered to express therapeutic molecules, have shown tremendous potential for cancer applications owing to their innate ability to home to tumors. However, traditional stem cell-based gene therapies are hampered by our current inability to control when the therapeutic genes are actually turned on, thereby resulting in detrimental side effects. Here, we report the novel application of magnetic core-shell nanoparticles for the dual purpose of delivering and activating a heat-inducible gene vector that encodes TNF-related apoptosis-inducing ligand (TRAIL) in adipose-derived mesenchymal stem cells (AD-MSCs). By combining the tumor tropism of the AD-MSCs with the spatiotemporal MCNP-based delivery and activation of TRAIL expression, this platform provides an attractive means with which to enhance our control over the activation of stem cell-based gene therapies. In particular, we found that these engineered AD-MSCs retained their innate ability to proliferate, differentiate, and, most importantly, home to tumors, making them ideal cellular carriers. Moreover, exposure of the engineered AD-MSCS to mild magnetic hyperthermia resulted in the selective expression of TRAIL from the engineered AD-MSCs and, as a result, induced significant ovarian cancer cell death in vitro and in vivo.

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“…45−47 Third, the AuNP backbone of NanoScript can be replaced with other types of nanoparticles, such as upconverting nanoparticles and magnetic core–shell nanoparticles, for potential applications such as tracking gene regulation in real time through infrared imaging or magnetic resonance imaging (MRI), respectively. 43,48 Finally, the most advantageous feature of NanoScript is its tunable components, by simply redesigning the hairpin polyamide DBD sequence to target regulatory genes such as those involved in differentiation. However, it should be noted that, due to the short DBD targeting sequence, there is a possibility for interactions with off-target genes; hence, further optimization by designing DBDs with longer sequences to target longer DNA sequences would further enhance the NanoScript platform.…”

Section: Discussionmentioning

confidence: 99%

NanoScript: A Nanoparticle-Based Artificial Transcription Factor for Effective Gene Regulation

et al. 2014

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Transcription factor (TF) proteins are master regulators of transcriptional activity and gene expression. TF-based gene regulation is a promising approach for many biological applications; however, several limitations hinder the full potential of TFs. Herein, we developed an artificial, nanoparticle-based transcription factor, termed NanoScript, which is designed to mimic the structure and function of TFs. NanoScript was constructed by tethering functional peptides and small molecules called synthetic transcription factors, which mimic the individual TF domains, onto gold nanoparticles. We demonstrate that NanoScript localizes within the nucleus and initiates transcription of a reporter plasmid by over 15-fold. Moreover, NanoScript can effectively transcribe targeted genes on endogenous DNA in a nonviral manner. Because NanoScript is a functional replica of TF proteins and a tunable gene-regulating platform, it has great potential for various stem cell applications.

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Multimodal Magnetic Core–Shell Nanoparticles for Effective Stem‐Cell Differentiation and Imaging

Cited by 72 publications

References 44 publications

Core–Shell Nanoparticle-Based Peptide Therapeutics and Combined Hyperthermia for Enhanced Cancer Cell Apoptosis

Core–Shell Nanoparticle-Based Peptide Therapeutics and Combined Hyperthermia for Enhanced Cancer Cell Apoptosis

Stem cell-based gene therapy activated using magnetic hyperthermia to enhance the treatment of cancer

NanoScript: A Nanoparticle-Based Artificial Transcription Factor for Effective Gene Regulation

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