Functionalized Superparamagnetic Iron Oxide Nanoparticles (SPIONs) as Platform for the Targeted Multimodal Tumor Therapy

Janko, Christina; Ratschker, Teresa; Nguyen, Khanh; Zschiesche, Lisa; Tietze, Rainer; Lyer, Stefan; Alexiou, Christoph

doi:10.3389/fonc.2019.00059

Cited by 81 publications

(56 citation statements)

References 90 publications

(94 reference statements)

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“…Similarly, it allows the immobilization of several targeting agents and therapeutic molecules that can dictate numerous functionalities [ 11 ]. This makes them suitable for a wide variety of biomedical applications including the delivery of therapeutics for cancer therapy [ 12 ], tissue repair [ 13 ], or neurodegeneration treatments [ 14 ], as well as nucleic acid delivery for gene therapy [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Tailoring Iron Oxide Nanoparticles for Efficient Cellular Internalization and Endosomal Escape

et al. 2020

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Iron oxide nanoparticles (IONs) have been widely explored for biomedical applications due to their high biocompatibility, surface-coating versatility, and superparamagnetic properties. Upon exposure to an external magnetic field, IONs can be precisely directed to a region of interest and serve as exceptional delivery vehicles and cellular markers. However, the design of nanocarriers that achieve an efficient endocytic uptake, escape lysosomal degradation, and perform precise intracellular functions is still a challenge for their application in translational medicine. This review highlights several aspects that mediate the activation of the endosomal pathways, as well as the different properties that govern endosomal escape and nuclear transfection of magnetic IONs. In particular, we review a variety of ION surface modification alternatives that have emerged for facilitating their endocytic uptake and their timely escape from endosomes, with special emphasis on how these can be manipulated for the rational design of cell-penetrating vehicles. Moreover, additional modifications for enhancing nuclear transfection are also included in the design of therapeutic vehicles that must overcome this barrier. Understanding these mechanisms opens new perspectives in the strategic development of vehicles for cell tracking, cell imaging and the targeted intracellular delivery of drugs and gene therapy sequences and vectors.

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Section: Introductionmentioning

confidence: 99%

Tailoring Iron Oxide Nanoparticles for Efficient Cellular Internalization and Endosomal Escape

et al. 2020

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“…Exemplarily, doxorubicin-loaded manganese dioxide nanoparticles have been accumulated by Amini et al in the tumor via the EPR effect, thus abolishing the immunosuppressive environment in an orthotopic mouse model of breast cancer [ 53 ]. To overcome immune escape mechanisms of the tumor cells and increase treatment efficacy, nanoparticles such as SPIONs might be loaded with additional molecules such as checkpoint inhibitors, serving as a platform for multimodal tumor therapy [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

Mitoxantrone-Loaded Nanoparticles for Magnetically Controlled Tumor Therapy–Induction of Tumor Cell Death, Release of Danger Signals and Activation of Immune Cells

et al. 2020

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Stimulating the patient`s immune system represents a promising therapeutic strategy to fight cancer. However, low immunogenicity of the tumor cells within an immune suppressive milieu often leads to weak anti-tumor immune responses. Additionally, the immune system may be impaired by accompanying aggressive chemotherapies. We show that mitoxantrone, bound to superparamagnetic iron oxide nanoparticles (SPIONs) as the transport system, can be magnetically accumulated in adherent HT-29 colon carcinoma cells, thereby inducing the same cell death phenotype as its soluble counterpart, a chemotherapeutic agent and prototypic inductor of immunogenic cell death. The nanoparticle-loaded drug induces cell cycle stop, apoptosis and secondary necrosis in a dose- and time-dependent manner comparable to the free drug. Cell death was accompanied by the release of interleukin-8 and damage-associated molecular patterns (DAMPs) such as HSP70 and ATP, which fostered chemotactic migration of monocytes and maturation of dendritic cells. We furthermore ensured absence of endotoxin contaminations and compatibility with erythrocytes and platelets and investigated the influence on plasma coagulation in vitro. Summarizing, with magnetic enrichment, mitoxantrone can be accumulated at the desired place, sparing healthy peripheral cells and tissues, such as immune cells. Conserving immune competence in cancer patients in the future might allow combined therapeutic approaches with immune therapies (e.g. checkpoint inhibitors).

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“…The coating of SPIONs with DEX offers desirable stability, with no toxicity recorded to date [ 10 ]. Furthermore, it provides a robust nanostructured platform for targeted therapeutic delivery [ 12 ]. DEX is a natural hydrophilic polymer that can be fully degraded in living biological systems, especially at an acidic pH.…”

Section: Introductionmentioning

confidence: 99%

Investigation of Dextran-Coated Superparamagnetic Nanoparticles for Targeted Vinblastine Controlled Release, Delivery, Apoptosis Induction, and Gene Expression in Pancreatic Cancer Cells

Albukhaty

Al-Musawi²,

Mahdi³

et al. 2020

Molecules

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In the current study, the surface of superparamagnetic iron oxide (SPION) was coated with dextran (DEX), and conjugated with folic acid (FA), to enhance the targeted delivery and uptake of vinblastine (VBL) in PANC-1 pancreatic cancer cells. Numerous analyses were performed to validate the prepared FA-DEX-VBL-SPION, such as field emission scanning transmission electron microscopy, high-resolution transmission electron microscopy, dynamic light scattering (DLS), Zeta Potential, Fourier transform infrared spectroscopy, and vibrating sample magnetometry (VSM). The delivery system capacity was evaluated by loading and release experiments. Moreover, in vitro biological studies, including a cytotoxicity study, cellular uptake assessment, apoptosis analysis, and real-time PCR, were carried out. The results revealed that the obtained nanocarrier was spherical with a suitable dispersion and without visible aggregation. Its average size, polydispersity, and zeta were 74 ± 13 nm, 0.080, and −45 mV, respectively. This dual functional nanocarrier also exhibited low cytotoxicity and a high apoptosis induction potential for successful VBL co-delivery. Real-time quantitative PCR analysis demonstrated the activation of caspase-3, NF-1, PDL-1, and H-ras inhibition, in PANC-1 cells treated with the FA-VBL-DEX-SPION nanostructure. Close inspection of the obtained data proved that the FA-VBL-DEX-SPION nanostructure possesses a noteworthy chemo-preventive effect on pancreatic cancer cells through the inhibition of cell proliferation and induction of apoptosis.

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Functionalized Superparamagnetic Iron Oxide Nanoparticles (SPIONs) as Platform for the Targeted Multimodal Tumor Therapy

Cited by 81 publications

References 90 publications

Tailoring Iron Oxide Nanoparticles for Efficient Cellular Internalization and Endosomal Escape

Tailoring Iron Oxide Nanoparticles for Efficient Cellular Internalization and Endosomal Escape

Mitoxantrone-Loaded Nanoparticles for Magnetically Controlled Tumor Therapy–Induction of Tumor Cell Death, Release of Danger Signals and Activation of Immune Cells

Investigation of Dextran-Coated Superparamagnetic Nanoparticles for Targeted Vinblastine Controlled Release, Delivery, Apoptosis Induction, and Gene Expression in Pancreatic Cancer Cells

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