Advances in Magnetic Nanoparticle-Driven Delivery of Gene Therapies towards Prostate Cancer

Conventional treatment possibilities for one of the most common diseases among men, i.e., prostate cancer has several side effects. Gene-based therapy such as siRNA, CRISPR/Cas9, pDNA, and miRNA have emerged as an alternative, combating posttherapy side effects and drug resistance. Magnetic nanoparticles have been appropriately modified and functionalized to efficiently deliver the gene therapy-based active compounds to prostate tumor cells. The main purpose of this review article is to highlight the strategies currently being utilized for the treatment of prostate cancer using magnetic nanoparticles for delivery of genetic material using both the passive and active (ligand-based) targeting. It further discusses the challenges in efficient delivery of therapeutics to tumor sites and their remedial approaches. Finally, it provides a glimpse of future advances for tumor-specific modifications of magnetic nanoparticles to combat prostate cancer.

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Polyethylenimine-coated gold-magnetic nanoparticles for ADAM10 siRNA delivery in prostate cancer cells

Journal of Bioactive and Compatible Polymers ◽

10.1177/0883911520960507 ◽

2020 ◽

Vol 35 (6) ◽

pp. 504-516

Author(s):

Raju Panday ◽

Ahmed ME Abdalla ◽

Yu Miao ◽

Xiaohong Li ◽

Manisha Neupane ◽

...

Keyword(s):

Prostate Cancer ◽

Magnetic Nanoparticles ◽

Sirna Delivery ◽

Medical Application ◽

Cell Viability Assay ◽

Tem Analysis ◽

Viability Assay ◽

Efficient Delivery ◽

Pc3 Cells

For an effective medical application of therapeutic siRNA, a safe and an efficient delivery system are required. Herein, magnetic nanoparticles (MNPs) have been successfully used as siRNA delivery vehicles. Firstly, MNPs were coated with gold (Au) nanoparticles and then capped with PEI. To improve the biocompatibility of nanoparticles, hyaluronic acid (HA) was coated onto the surface of PEI-Au/Fe nanoparticles. The prepared HA-PEI-Au/Fe3O4 nanoparticles were characterized and found to be uniform and well segregated in TEM analysis. FTIR analysis confirmed that HA was successfully conjugated to PEI. The polymer content in these nanoparticles was relatively higher than PEG coated nanoparticles. Cell viability assay demonstrated that the nanoparticles were relatively biocompatible in nature. ADAM10 siRNA was loaded into the HA-PEI-Au/Fe3O4 nanoparticles and cytotoxicity to prostate cancer (PC3) cells was analyzed. The results indicate that ADAM10 siRNA loaded HA-PEI-Au/Fe3O4 suppress the PC3 cells growth in vitro. Clearly, it could be confirmed that HA-PEI coated Au/Fe3O4 nanoparticles with higher biocompatibility appear to be suitable for intracellular siRNA delivery.

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Investigating Mindfulness and Music to Ease Radiation Side Effects in Prostate Cancer

Case Medical Research ◽

10.31525/ct1-nct03852017 ◽

2019 ◽

Author(s):

Keyword(s):

Prostate Cancer ◽

Side Effects ◽

Radiation Side Effects

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Understanding intracellular nanoparticle trafficking fates through spatiotemporally resolved magnetic nanoparticle recovery

Nanoscale Advances ◽

10.1039/d0na01035a ◽

2021 ◽

Author(s):

Emily Sheridan ◽

Silvia Vercellino ◽

Lorenzo Cursi ◽

Laurent Adumeau ◽

James A. Behan ◽

...

Keyword(s):

Decision Making ◽

Magnetic Nanoparticles ◽

Magnetic Nanoparticle ◽

Magnetic Extraction

We describe how magnetic nanoparticles can be used to study intracellular nanoparticle trafficking, and how magnetic extraction may be integrated with downstream analyses to investigate nanoscale decision-making events.

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Therapeutic Potential of Magnetic Nanoparticle-Based Human Adipose-Derived Stem Cells in a Mouse Model of Parkinson’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22020654 ◽

2021 ◽

Vol 22 (2) ◽

pp. 654

Author(s):

Ka Young Kim ◽

Keun-A Chang

Keyword(s):

Parkinson’S Disease ◽

Stem Cells ◽

Parkinson's Disease ◽

Magnetic Nanoparticles ◽

Substantia Nigra ◽

Mouse Model ◽

Magnetic Nanoparticle ◽

Imaging System ◽

Therapeutic Potential ◽

Adipose Derived Stem Cells

Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra. Several treatments for PD have focused on the management of physical symptoms using dopaminergic agents. However, these treatments induce various adverse effects, including hallucinations and cognitive impairment, owing to non-targeted brain delivery, while alleviating motor symptoms. Furthermore, these therapies are not considered ultimate cures owing to limited brain self-repair and regeneration abilities. In the present study, we aimed to investigate the therapeutic potential of human adipose-derived stem cells (hASCs) using magnetic nanoparticles in a 6-hydroxydopamine (6-OHDA)-induced PD mouse model. We used the Maestro imaging system and magnetic resonance imaging (MRI) for in vivo tracking after transplantation of magnetic nanoparticle-loaded hASCs to the PD mouse model. The Maestro imaging system revealed strong hASCs signals in the brains of PD model mice. In particular, MRI revealed hASCs distribution in the substantia nigra of hASCs-injected PD mice. Behavioral evaluations, including apomorphine-induced rotation and rotarod performance, were significantly recovered in hASCs-injected 6-OHDA induced PD mice when compared with saline-treated counterparts. Herein, we investigated whether hASCs transplantation using magnetic nanoparticles recovered motor functions through targeted brain distribution in a 6-OHDA induced PD mice. These results indicate that magnetic nanoparticle-based hASCs transplantation could be a potential therapeutic strategy in PD.

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Men’s experiences of radiotherapy treatment for localized prostate cancer and its long-term treatment side effects: a longitudinal qualitative study

Cancer Causes & Control ◽

10.1007/s10552-020-01380-3 ◽

2021 ◽

Author(s):

E. Sutton ◽

◽

J. A. Lane ◽

M. Davis ◽

E. I. Walsh ◽

...

Keyword(s):

Prostate Cancer ◽

Side Effects ◽

External Beam Radiotherapy ◽

Qualitative Interviews ◽

Well Being ◽

Localized Prostate Cancer ◽

Short Term ◽

Age Related ◽

Qualitative Interview Study ◽

Long Term Treatment

Abstract Purpose To investigate men’s experiences of receiving external-beam radiotherapy (EBRT) with neoadjuvant Androgen Deprivation Therapy (ADT) for localized prostate cancer (LPCa) in the ProtecT trial. Methods A longitudinal qualitative interview study was embedded in the ProtecT RCT. Sixteen men with clinically LPCa who underwent EBRT in ProtecT were purposively sampled to include a range of socio-demographic and clinical characteristics. They participated in serial in-depth qualitative interviews for up to 8 years post-treatment, exploring experiences of treatment and its side effects over time. Results Men experienced bowel, sexual, and urinary side effects, mostly in the short term but some persisted and were bothersome. Most men downplayed the impacts, voicing expectations of age-related decline, and normalizing these changes. There was some reticence to seek help, with men prioritizing their relationships and overall health and well-being over returning to pretreatment levels of function. Some unmet needs with regard to information about treatment schedules and side effects were reported, particularly among men with continuing functional symptoms. Conclusions These findings reinforce the importance of providing universal clear, concise, and timely information and supportive resources in the short term, and more targeted and detailed information and care in the longer term to maintain and improve treatment experiences for men undergoing EBRT.

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The Ocular Gene Delivery Landscape

Biomolecules ◽

10.3390/biom11081135 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1135

Author(s):

Bhubanananda Sahu ◽

Isha Chug ◽

Hemant Khanna

Keyword(s):

Gene Therapy ◽

Genetic Diseases ◽

Gene Therapies ◽

Advantages And Disadvantages ◽

Fda Approval ◽

New Information ◽

Efficient Delivery ◽

Delivery Routes ◽

History Of ◽

Different Parts

The eye is at the forefront of developing therapies for genetic diseases. With the FDA approval of the first gene-therapy drug for a form of congenital blindness, numerous studies have been initiated to develop gene therapies for other forms of eye diseases. These examinations have revealed new information about the benefits as well as restrictions to using drug-delivery routes to the different parts of the eye. In this article, we will discuss a brief history of gene therapy and its importance to the eye and ocular delivery landscape that is currently being investigated, and provide insights into their advantages and disadvantages. Efficient delivery routes and vehicle are crucial for an effective, safe, and longer-lasting therapy.

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Characterization of Recombinant Adeno-Associated Viruses (rAAVs) for Gene Therapy Using Orthogonal Techniques

Pharmaceutics ◽

10.3390/pharmaceutics13040586 ◽

2021 ◽

Vol 13 (4) ◽

pp. 586

Author(s):

Liam Cole ◽

Diogo Fernandes ◽

Maryam T. Hussain ◽

Michael Kaszuba ◽

John Stenson ◽

...

Keyword(s):

Gene Therapy ◽

Light Scattering ◽

Dynamic Light Scattering ◽

Viral Vector ◽

Structural Characteristics ◽

Genetic Material ◽

Label Free ◽

Gene Therapies ◽

Multiple Challenges

Viruses are increasingly used as vectors for delivery of genetic material for gene therapy and vaccine applications. Recombinant adeno-associated viruses (rAAVs) are a class of viral vector that is being investigated intensively in the development of gene therapies. To develop efficient rAAV therapies produced through controlled and economical manufacturing processes, multiple challenges need to be addressed starting from viral capsid design through identification of optimal process and formulation conditions to comprehensive quality control. Addressing these challenges requires fit-for-purpose analytics for extensive characterization of rAAV samples including measurements of capsid or particle titer, percentage of full rAAV particles, particle size, aggregate formation, thermal stability, genome release, and capsid charge, all of which may impact critical quality attributes of the final product. Importantly, there is a need for rapid analytical solutions not relying on the use of dedicated reagents and costly reference standards. In this study, we evaluate the capabilities of dynamic light scattering, multiangle dynamic light scattering, and SEC–MALS for analyses of rAAV5 samples in a broad range of viral concentrations (titers) at different levels of genome loading, sample heterogeneity, and sample conditions. The study shows that DLS and MADLS® can be used to determine the size of full and empty rAAV5 (27 ± 0.3 and 33 ± 0.4 nm, respectively). A linear range for rAAV5 size and titer determination with MADLS was established to be 4.4 × 1011–8.7 × 1013 cp/mL for the nominally full rAAV5 samples and 3.4 × 1011–7 × 1013 cp/mL for the nominally empty rAAV5 samples with 3–8% and 10–37% CV for the full and empty rAAV5 samples, respectively. The structural stability and viral load release were also inferred from a combination of DLS, SEC–MALS, and DSC. The structural characteristics of the rAAV5 start to change from 40 °C onward, with increasing aggregation observed. With this study, we explored and demonstrated the applicability and value of orthogonal and complementary label-free technologies for enhanced serotype-independent characterization of key properties and stability profiles of rAAV5 samples.

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Simulated Clustering Dynamics of Colloidal Magnetic Nanoparticles

Nanoscale ◽

10.1039/d0nr08561h ◽

2021 ◽

Author(s):

Frederik Laust Durhuus ◽

Lau Halkier Wandall ◽

Mathias Hoeg Boisen ◽

Mathias Kure ◽

Marco Beleggia ◽

...

Keyword(s):

Magnetic Nanoparticles ◽

Self Assembly ◽

Biomedical Applications ◽

Magnetic Nanoparticle ◽

Bottom Up ◽

Novel Materials ◽

Nanoparticle Clusters ◽

Clustering Dynamics

Magnetically guided self-assembly of nanoparticles is a promising bottom-up method to fabricate novel materials and superstructures, such as, for example, magnetic nanoparticle clusters for biomedical applications. The existence of assembled...

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Transient cell stiffening triggered by magnetic nanoparticle exposure

Journal of Nanobiotechnology ◽

10.1186/s12951-021-00790-y ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Jose E. Perez ◽

Florian Fage ◽

David Pereira ◽

Ali Abou-Hassan ◽

Sophie Asnacios ◽

...

Keyword(s):

Mechanical Properties ◽

Magnetic Nanoparticles ◽

Magnetic Nanoparticle ◽

Early Time ◽

Population Level ◽

Short Time Scale ◽

Initial Contact ◽

Almost All ◽

The Impact ◽

Stiffening Effect

Abstract Background The interactions between nanoparticles and the biological environment have long been studied, with toxicological assays being the most common experimental route. In parallel, recent growing evidence has brought into light the important role that cell mechanics play in numerous cell biological processes. However, despite the prevalence of nanotechnology applications in biology, and in particular the increased use of magnetic nanoparticles for cell therapy and imaging, the impact of nanoparticles on the cells’ mechanical properties remains poorly understood. Results Here, we used a parallel plate rheometer to measure the impact of magnetic nanoparticles on the viscoelastic modulus G*(f) of individual cells. We show how the active uptake of nanoparticles translates into cell stiffening in a short time scale (< 30 min), at the single cell level. The cell stiffening effect is however less marked at the cell population level, when the cells are pre-labeled under a longer incubation time (2 h) with nanoparticles. 24 h later, the stiffening effect is no more present. Imaging of the nanoparticle uptake reveals almost immediate (within minutes) nanoparticle aggregation at the cell membrane, triggering early endocytosis, whereas nanoparticles are almost all confined in late or lysosomal endosomes after 2 h of uptake. Remarkably, this correlates well with the imaging of the actin cytoskeleton, with actin bundling being highly prevalent at early time points into the exposure to the nanoparticles, an effect that renormalizes after longer periods. Conclusions Overall, this work evidences that magnetic nanoparticle internalization, coupled to cytoskeleton remodeling, contributes to a change in the cell mechanical properties within minutes of their initial contact, leading to an increase in cell rigidity. This effect appears to be transient, reduced after hours and disappearing 24 h after the internalization has taken place.

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