Targeting of drug-loaded nanoparticles to tumor sites increases cell death and release of danger signals

Alev, Magdalena; Egenberger, Laura; Mühleisen, Laura; Weigel, Bianca; Frey, Benjamin; Friedrich, Ralf P.; Pöttler, Marina; Janko, Christina

doi:10.1016/j.jconrel.2018.07.007

Cited by 20 publications

(24 citation statements)

References 77 publications

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“…This resulted in SPION MTO particles, as MTO binds strongly to the HSA corona, with a corresponding concentration of 410 µM MTO. Non-loaded SPIONs and drug-loaded SPION MTO were characterized previously for physicochemical features ( Table 1 ) [ 28 , 29 ].…”

Section: Methodsmentioning

confidence: 99%

“…In tumor-bearing rabbits, the tumor continuously shrank after treatment with MTO loaded SPIONs until it was completely dematerialized after several weeks [ 26 ], suggesting an immune-mediated rejection rather than complete tumor lysis by the drug. In a previous study, we found that cell death induced by MTO loaded onto SPIONs was accompanied by the release of danger signals in Jurkat cells, with concomitant activation of dendritic cells [ 28 ] with comparable efficacy, as may be observed with administration of the free drug. Based on these earlier findings, we further investigated the effects of MTO loaded on SPIONs in HT-29 colon carcinoma cells and its biocompatibility in blood.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

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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“…As shown in Figure 3C, the Pearson correlation index increased as a function of incubation time, which suggested that MIT in the nucleus was positively related to time. Only free MIT molecules can enter the nuclei and are prone to remaining in the nuclei instead of the plasma, 47 suggesting that quite a number of MIT molecules loaded to PL/ACC-MIT nanoparticles were released in the free form after internalization. The clearly observed MIT signals in the nuclei, in contrast to the negligible extracellular drug release within 4 hours in the drug release assay, also suggested that intracellular drug release of PL/ACC-MIT nanoparticles might follow a different and faster mechanism.…”

Section: In Vitro Drug Localizationmentioning

confidence: 99%

<p>Mitoxantrone-preloaded water-responsive phospholipid-amorphous calcium carbonate hybrid nanoparticles for targeted and effective cancer therapy</p>

Wang¹,

Han²,

Liu³

et al. 2019

IJN

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Background: The application of mitoxantrone (MIT) in cancer therapy has been severely limited by its inherent drawbacks. In addition, effective cancer therapy calls for drug release systems capable of enforcing drug release within cancer cells in response to infinite stimulant with enhanced drug penetration capability. Methods: MIT-preloaded phospholipid-amorphous calcium carbonate hybrid nanoparticles (PL/ACC-MIT) that surface modified with PL shell (containing shielding polymer polyethylene glycol and targeting moiety folic acid) were prepared by a facile solvent-diffusion method. Results: It has been proven that the resulting PL/ACC-MIT nanoparticles demonstrated satisfactory stability against various aqueous environments with minimal drug leakage and exerted strong targeting capability but selective preference to the folate receptor-overexpressing cell line. In contrast, once exposed to the enzyme-abundant and acidic environments of cancer cells, the PL/ACC-MIT nanoparticles can readily decompose to facilitate quick drug release and enhanced drug penetration to yield preferable antitumor effect both in vitro and in vivo. Conclusion: In this study, MIT-preloaded water-responsive hybrid nanoparticles with increased stability, targetability, controlled drug release, and enhanced drug penetration were successfully developed, which might be a candidate for targeted and effective cancer therapy.

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“…Although decades of efforts of research and billions of funding have enhanced our understanding of the underlying mechanisms of tumorigenesis, the death rate from cancer remains running at a high level nowadays [1]. Innovative strategies fighting cancer by inducing antitumor responses from the immune system are urgently needed [2,3]. Chemotherapeutics from the class of the anthracyclines have been shown to induce the death of cancer cells with immunogenic features and triggering immunogenic antitumor responses [4].…”

Section: Introductionmentioning

confidence: 99%

TfR mAb-Cross-Linked Rituximab/MTX-PEG-PLL-PLGA Drug-Loaded Nanoparticles Enhance Anticancer Action in B Lymphocytes

Liu

Zhao

Wang³

et al. 2019

Journal of Nanomaterials

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Nanoparticles could enhance the drug targeted to the cancer cell by the enrichment of the drug levels, which leads to the improvement of the codelivery of both drugs for an antitumor effect. In the current study, we reported an efficient, local drugloaded delivery strategy with a nanoparticle-loaded system. After the synthesis of Rituximab/MTX-PEG-PLL-PLGA, the transferrin receptor monoantibody (TfR mAb) was subsequently cross-linked to the nanoparticles. Compared to the traditional drug, the nanoparticle-loaded system can precisely and efficiently transport the Rituximab and Methotrexate (MTX) drug into SU-DHL-4 cells, a typical kind of B lymphocytes, which can significantly increase the cell apoptosis in the SU-DHL-4 cells. Thus, the multifunctional drug-loaded nanoparticles displayed the persistent stability and precise targeting properties, which enhanced the efficiency of anticancer efficiency in B lymphocytes.

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Targeting of drug-loaded nanoparticles to tumor sites increases cell death and release of danger signals

Cited by 20 publications

References 77 publications

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

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

<p>Mitoxantrone-preloaded water-responsive phospholipid-amorphous calcium carbonate hybrid nanoparticles for targeted and effective cancer therapy</p>

TfR mAb-Cross-Linked Rituximab/MTX-PEG-PLL-PLGA Drug-Loaded Nanoparticles Enhance Anticancer Action in B Lymphocytes

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