Abstract
Carbon nanostructures (CN) are emerging valuable materials for the assembly of highly engineered multifunctional nanovehicles for cancer therapy, in particular for counteracting the insurgence of multi-drug resistance (MDR). In this regard, carbon nanotubes (CNT), graphene oxide (GO), and fullerenes (F) have been proposed as promising materials due to their superior physical, chemical, and biological features. The possibility to easily modify their surface, conferring tailored properties, allows different CN derivatives to be synthesized. Although many studies have explored this topic, a comprehensive review evaluating the beneficial use of functionalized CNT vs G or F is still missing. Within this paper, the most relevant examples of CN-based nanosystems proposed for MDR reversal are reviewed, taking into consideration the functionalization routes, as well as the biological mechanisms involved and the possible toxicity concerns. The main aim is to understand which functional CN represents the most promising strategy to be further investigated for overcoming MDR in cancer.
Highlights
The USA National Cancer Institute defines cancer as several diseases characterized by an uncontrollable proliferation of abnormal cells invading surrounding tissues [1], with over 10 million new cases diagnosed each year with a survival rate of around 40% [2]
The latter property was exploited by Li et al [146], who developed a DOX carrier system based on graphene oxide (GO) modified with two molecular beacons (MBs)
4-styrenesulfonates) (PSS) was used for the combined DOX delivery and miR-21 gene silencing in drug-resistant breast cancer cells [158]. miR-21 over-expression is significantly correlated with drug resistance in breast cancer, the simultaneous down-regulation of miR-21 gene and the enhanced cell accumulation of DOX was proposed as a valuable strategy for re-sensitizing resistant cells to the cytotoxic agent
Summary
Different nanomaterials, including metal-based (e.g., iron, silver, and gold nanoparticles), carbon-based (e.g., carbon nanotubes, graphene), and polymer-based (e.g., polymer therapeutics and polymer nanoparticles) materials, have been proposed for various aspects of cancer therapy. Such materials, often combined in composite systems, have gained intense research interest due to their ability to enhance the therapeutic effectiveness and reduce the systemic side effects of conventional cytotoxic drugs [9] (Figure 1). F are irregular stacked graphene sheets arranged in hollow spherical or ellipsoid structures, where carbon atoms form hexagonal or pentagonal rings.
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