Melanoma is one of the deadliest forms of cancer, for which therapeutic regimens are usually limited by the development of resistance. Here, we fabricated FeO nanoparticle clusters (NPCs), which have drawn widespread attention, and investigated their role in the treatment of melanoma by photothermal therapy (PTT). Scanning electron microscopy imaging shows that our synthesized NPCs are spherical with an average diameter of 329.2 nm. They are highly absorptive at the near-infrared wavelength of 808 nm and efficient at locally converting light into heat. In vitro experiments using light-field microscopy and cell viability assay showed that FeO NPCs, in conjunction with near-infrared irradiation, effectively ablated A375 melanoma cells by inducing overt apoptosis. Consistently, in vivo studies using BALB/c mice found that intratumoral administration of FeO NPCs and concomitant in situ exposure to near-infrared light significantly inhibited the growth of implanted tumor xenografts. Finally, we revealed, by experimental approaches including semi-quantitative PCR, western blot and immunohistochemistry, the heat shock protein HSP70 to be upregulated in response to PTT, suggesting this chaperone protein could be a plausible underlying mechanism for the observed therapeutic outcome. Altogether, our results highlight the promise of FeO NPCs as a new PTT option to treat melanoma.
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http://dx.doi.org/10.3762/bjnano.13.20 | DOI Listing |
J Clin Invest
November 2017
Neuroimmunology Unit.
In multiple sclerosis, the pathological interaction between autoreactive Th cells and mononuclear phagocytes in the CNS drives initiation and maintenance of chronic neuroinflammation. Here, we found that intrathecal transplantation of neural stem/precursor cells (NPCs) in mice with experimental autoimmune encephalomyelitis (EAE) impairs the accumulation of inflammatory monocyte-derived cells (MCs) in the CNS, leading to improved clinical outcome. Secretion of IL-23, IL-1, and TNF-α, the cytokines required for terminal differentiation of Th cells, decreased in the CNS of NPC-treated mice, consequently inhibiting the induction of GM-CSF-producing pathogenic Th cells.
View Article and Find Full Text PDFImmunol Lett
December 2015
Institute of Experimental Neurology (INSpe), Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy. Electronic address:
Owing to their unique immunomodulatory properties, mesenchymal stem cells (MSCs) have been advocated as a potential therapy for numerous pathological conditions in which immune-mediated inflammatory reactions play a crucial role, such as autoimmune disorders, cerebrovascular diseases and tumours. Increasing evidence suggest that stem cells, other than MSCs, are also capable of immunomodulation. Neural stem/precursor cells (NPCs) have been among the first stem cells to show immunomodulatory properties and nowadays represent one the most studied and promising stem cell subtype in still uncurable acute and chronic inflammatory neurological disorders.
View Article and Find Full Text PDFNat Commun
June 2014
Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), Division of Neuroscience, San Raffaele Scientific Institute, 20132 Milan, Italy.
The possibility of generating neural stem/precursor cells (NPCs) from induced pluripotent stem cells (iPSCs) has opened a new avenue of research that might nurture bench-to-bedside translation of cell transplantation protocols in central nervous system myelin disorders. Here we show that mouse iPSC-derived NPCs (miPSC-NPCs)-when intrathecally transplanted after disease onset-ameliorate clinical and pathological features of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Transplanted miPSC-NPCs exert the neuroprotective effect not through cell replacement, but through the secretion of leukaemia inhibitory factor that promotes survival, differentiation and the remyelination capacity of both endogenous oligodendrocyte precursors and mature oligodendrocytes.
View Article and Find Full Text PDFCurr Opin Neurol
June 2012
Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
Purpose Of Review: Transplantation of neural stem/precursor cells (NPCs) has been proposed as a promising therapeutic strategy in almost all neurological disorders characterized by the failure of central nervous system (CNS) endogenous repair mechanisms in restoring the tissue damage and rescuing the lost function. Nevertheless, recent evidence consistently challenges the limited view that transplantation of these cells is solely aimed at protecting the CNS from inflammatory and neurodegenerative damage through cell replacement.
Recent Findings: Recent preclinical data confirmed that transplanted NPCs may also exert a 'bystander' neuroprotective effect and identified a series of molecules - for example, immunomodulatory substances, neurotrophic growth factors, stem cell regulators as well as guidance molecules - whose in-situ secretion by NPCs is temporally and spatially orchestrated by environmental needs.
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