Direct Transfer of Mesoporous Silica Nanoparticles between Macrophages and Cancer Cells

Franco, Stefan; Noureddine, Achraf; Guo, Jimin; Keth, Jane; Paffett, Michael L.; Brinker, C. Jeffrey; Serda, Rita E.

doi:10.3390/cancers12102892

Cited by 23 publications

(23 citation statements)

References 63 publications

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“…Indeed, MSN uptake into cells has already been demonstrated for primary splenocytes, primary macrophages, and other macrophage cell lines. 34,52,53 T lymphocytes, on the other hand, were only MSNpositive at higher concentrations. Since T lymphocytes are not professional antigen-presenting cells, this phenotype might rather be due to an attachment of the particles to the cell surface.…”

Section: Resultsmentioning

confidence: 90%

Mesoporous Silica Nanoparticles as pH-Responsive Carrier for the Immune-Activating Drug Resiquimod Enhance the Local Immune Response in Mice

et al. 2021

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Nanoparticle-based delivery systems for cancer immunotherapies aim to improve the safety and efficacy of these treatments through local delivery to specialized antigenpresenting cells (APCs). Multifunctional mesoporous silica nanoparticles (MSNs), with their large surface areas, their tunable particle and pore sizes, and their spatially controlled functionalization, represent a safe and versatile carrier system. In this study, we demonstrate the potential of MSNs as a pHresponsive drug carrier system for the anticancer immunestimulant R848 (resiquimod), a synthetic Toll-like receptor 7 and 8 agonist. Equipped with a biotin−avidin cap, the tailormade nanoparticles showed efficient stimuli-responsive release of their R848 cargo in an environmental pH of 5.5 or below. We showed that the MSNs loaded with R848 were rapidly taken up by APCs into the acidic environment of the lysosome and that they potently activated the immune cells. Upon subcutaneous injection into mice, the particles accumulated in migratory dendritic cells (DCs) in the draining lymph nodes, where they strongly enhanced the activation of the DCs. Furthermore, simultaneous delivery of the model antigen OVA and the adjuvant R848 by MSNs resulted in an augmented antigen-specific T-cell response. The MSNs significantly improved the pharmacokinetic profile of R848 in mice, as the half-life of the drug was increased 6-fold, and at the same time, the systemic exposure was reduced. In summary, we demonstrate that MSNs represent a promising tool for targeted delivery of the immune modulator R848 to APCs and hold considerable potential as a carrier for cancer vaccines.

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Section: Resultsmentioning

confidence: 90%

Mesoporous Silica Nanoparticles as pH-Responsive Carrier for the Immune-Activating Drug Resiquimod Enhance the Local Immune Response in Mice

et al. 2021

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“…The cellular uptake of VMWNPs was quantified with 24 h of incubation of 25-500 µg/mL, delivered in media with or without FBS (without FBS was used to promote cellular uptake by serum starving the cells). Previous literature has demonstrated that serum starving cells, or failing to provide FBS, can further facilitate the uptake of nanoparticles [36,38]. With FBS in the media, OxS CT-26 cells had 0 µg/mL when exposed to 25 or 50 µg/mL of VMWNPs (Supplementary Figure S5a).…”

Section: Quantification Of Intracellular Vmwnpsmentioning

confidence: 93%

“…The increase in cell viability for OxR RKO cells at lower oxaliplatin concentrations was an effect that was observed multiple times with this oxaliplatin-resistant cell line. The phenomenon may be described as a hormetic effect, wherein low concentrations of a toxic agent can stimulate cell growth [34][35][36]. It is an interesting observation that OxR HT-29 cells did not exhibit this effect.…”

Section: Augmented Response To Oxaliplatin Using Hyperthermiamentioning

confidence: 99%

Variable Molecular Weight Polymer Nanoparticles for Detection and Hyperthermia-Induced Chemotherapy of Colorectal Cancer

Sarkar

Levi

2021

Cancers

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Oxaliplatin plays a significant role as a chemotherapeutic agent for the treatment of colorectal cancer (CRC); however, oxaliplatin-resistant phenotypes make further treatment challenging. Here, we have demonstrated that rapid (60 s) hyperthermia (42 °C), generated by the near-infrared stimulation of variable molecular weight nanoparticles (VMWNPs), increases the effectiveness of oxaliplatin in the oxaliplatin-resistant CRC cells. VMWNP-induced hyperthermia resulted in a higher cell death in comparison to cells exposed to chemotherapy at 42 °C for 2 h. Fluorescence from VMWNPs was observed inside cells, which allows for the detection of CRC. The work further demonstrates that the intracellular thermal dose can be determined using cell luminescence and correlated with the cell viability and response to VMWNP-induced chemotherapy. Mild heating makes oxaliplatin-resistant cancer cells responsive to chemotherapy, and the VMWNPs-induced hyperthermia can induce cell death in a few minutes, compared to classical bulk heating. The results presented here lay the foundation for photothermal polymer nanoparticles to be used for cell ablation and augmenting chemotherapy in drug-resistant colorectal cancer cells.

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“…It has been shown that fluorescently labelled silica nanoparticles can be transferred between tumor cells by TNTs [131]. Franco S et al demonstrated the intercellular trafficking of mesoporus silica nanoparticles along TNTs and TMs between macrophages and cancer cells in vitro and in vivo [132]. A recent paper from our group reported the exchange of multifunctional liposomes between human GBM cells and healthy astrocytes in vitro.…”

Section: Exploiting Tnts As Drug Delivery Channelsmentioning

confidence: 97%

The 3.0 Cell Communication: New Insights in the Usefulness of Tunneling Nanotubes for Glioblastoma Treatment

Taiarol

Formicola

Fagioli

et al. 2021

Cancers

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Glioblastoma (GBM) is a particularly challenging brain tumor characterized by a heterogeneous, complex, and multicellular microenvironment, which represents a strategic network for treatment escape. Furthermore, the presence of GBM stem cells (GSCs) seems to contribute to GBM recurrence after surgery, and chemo- and/or radiotherapy. In this context, intercellular communication modalities play key roles in driving GBM therapy resistance. The presence of tunneling nanotubes (TNTs), long membranous open-ended channels connecting distant cells, has been observed in several types of cancer, where they emerge to steer a more malignant phenotype. Here, we discuss the current knowledge about the formation of TNTs between different cellular types in the GBM microenvironment and their potential role in tumor progression and recurrence. Particularly, we highlight two prospective strategies targeting TNTs as possible therapeutics: (i) the inhibition of TNT formation and (ii) a boost in drug delivery between cells through these channels. The latter may require future studies to design drug delivery systems that are exchangeable through TNTs, thus allowing for access to distant tumor niches that are involved in tumor immune escape, maintenance of GSC plasticity, and increases in metastatic potential.

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Direct Transfer of Mesoporous Silica Nanoparticles between Macrophages and Cancer Cells

Cited by 23 publications

References 63 publications

Mesoporous Silica Nanoparticles as pH-Responsive Carrier for the Immune-Activating Drug Resiquimod Enhance the Local Immune Response in Mice

Mesoporous Silica Nanoparticles as pH-Responsive Carrier for the Immune-Activating Drug Resiquimod Enhance the Local Immune Response in Mice

Variable Molecular Weight Polymer Nanoparticles for Detection and Hyperthermia-Induced Chemotherapy of Colorectal Cancer

The 3.0 Cell Communication: New Insights in the Usefulness of Tunneling Nanotubes for Glioblastoma Treatment

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