Therapeutic Use of Inorganic Nanomaterials in Malignant Diseases
Neoplastic disease has multifactorial etiology and insidious evolution which make it unlikely to be detected in early stages and very difficult to treat at later times. The effectiveness of standard therapeutic approaches is limited by severe adverse effects, metastasis, and tumor capacity to develop multidrug resistance.
The success of inorganic nanomaterial-based therapeutic agents depends on the degree to which these nanostructures satisfy general requirements for drug safety regarding biocompatibility, biodegradability, and stability and on their antitumor efficacy. Fabrication of such nanomedicines requires adequate assessment and engineering of nanomaterial physicochemical characteristics like particle size, specific surface area, surface charge, hydrodynamic size, and magnetic, optical, and photocatalytic properties. Together with surface functionalization and delivery method, these properties dictate the in vivo “biological identity” of the nanomaterial and its fate with respect to cellular uptake and distribution/accumulation inside the body.
Nanocarriers for therapeutic agents and active targeting ligands for molecules overexpressed on tumor tissues as well as for altered signal transduction pathways. Inorganic nanomaterial-based therapeutic agents are able to reduce tumor growth acting on neoplastic vasculature (by inhibiting angiogenesis, vasculogenesis, and vasculogenic mimicry) or on malignant cells (blocking activation of overexpressed receptors and their specific signaling pathways, inducing oxidative stress, and reducing multidrug resistance). Moreover, inorganic nanomaterials are able to inhibit tumor invasiveness and metastasis by reducing degradation of extracellular matrix, exosome secretion, and cell proliferation at the secondary site.
- 2.Contrast agents and medical adhesives in cancer surgery:
Vital staining of sentinel lymph nodes (SLNs) where the first metastasis appears – the use of carbon nanoparticles, single-walled and multilayer carbon nanotubes, or superparamagnetic iron oxide nanoparticles was associated with a significantly higher number of harvested SLNs in breast and cervical tumors, lung cancer, papillary thyroid carcinoma, and prostate carcinoma.
Nanoparticle-based medical adhesives used for surgical wound closure – aqueous suspensions of iron oxide and silicon dioxide nanoparticles were shown to rapidly connect highly vascularized tissues (e.g., liver).
Inorganic sensitizers for radiotherapy – gold nanoparticles were reported to significantly enhance the efficiency of ionizing radiation and induce targeted cancer cell apoptosis, tumor growth inhibition, and increases of survival rates in tumor-bearing mice.
Antitumor agents based on specific material properties like surface plasmon resonance (photothermal heating), magnetic responsiveness (magnetic hyperthermia), and photocatalysis (photodynamic therapy) – heat generated by plasmonic (gold-based) or magnetic (iron oxide-based) nanomaterials exposed to laser light or alternating magnetic fields, respectively, was shown to efficiently destroy tumors in mouse models or leads to promising results in clinical trials; the antitumor action of photoactivated TiO2-based nanomedicines was assessed in numerous in vitro and several in vivo studies.
Adjuvant therapy (iron replacement therapy) – iron oxide colloids (IOC) are more efficient than free iron in treating iron-deficient anemia associated with cancer.
Overall, inorganic-organic therapeutic nanoplatforms provide enhanced treatment efficiency, reduced adverse effects, multiple antitumor action mechanisms, facile cell internalization, and diminished multidrug resistance.
KeywordsCancer Inorganic nanomaterials Targeted therapy Nano-sized drug delivery system Hyperthermia Plasmonic photothermal therapy Photodynamic therapy
Author Traian Popescu acknowledges funding from Romanian National Authority for Scientific Research, under Core Project PN16480101, and from Romanian Ministry of Research and Innovation, CCCDI – UEFISCDI, under national grant PN-III-P1-1.2-PCCDI-2017-0062/contract no. 58/component project no.1. Author Andreea-Roxana Lupu acknowledges support under PN-II-PT-PCCA-2013-4-1386 (NANOPATCH) and PN-III-P1-1.2-PCCDI-2017-0062/contract no. 58/component project no.1. Andreea-Roxana Lupu and Marko Stojanović were also supported by South East Europe Cooperation, University of Hamburg.
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