ABSTRACT
The remote control of biocatalytic processes in an extracellular medium is an exciting idea to deliver innovative solutions in the biocatalysis field. With this purpose, metallic nanoparticles (NPs) are great candidates, as their inherent thermal, electric, magnetic, and plasmonic properties can readily be manipulated upon external stimuli. Exploring the unique NP properties beyond an anchoring platform for enzymes brings up the opportunity to extend the efficiency of biocatalysts and modulate their activity through triggered events. In this review, we discuss a set of external stimuli, such as light, electricity, magnetism, and temperature, as tools for the regulation of nanobiocatalysis, including the challenges and perspectives regarding their use. In addition, we elaborate on the use of combined stimuli that create a more refined framework in terms of a multiresponsive system. Finally, we envision this review might instigate researchers in this field of study with a set of promising opportunities in the near future.
Subject(s)
TemperatureABSTRACT
Gold nanoparticle (AuNP)-based systems have been extensively investigated as diagnostic and therapeutic agents due to their tunable properties and easy surface functionalization. Upon cell uptake, AuNPs present an inherent cell impairment potential based on organelle and macromolecules damage, leading to cell death. Such cytotoxicity is concentration-dependent and completely undesirable, especially if unspecific. However, under non-cytotoxic concentrations, internalized AuNPs could potentially weaken cells and act as antitumor agents. Therefore, this study aimed to investigate the antitumor effect of ultrasmall AuNPs (~3 nm) stabilized by the anionic polysaccharide gum arabic (GA-AuNPs). Other than intrinsic cytotoxicity, the focus was downregulation of cancer hallmarks of aggressive tumors, using a highly metastatic model of melanoma. We first demonstrated that GA-AuNPs showed excellent stability under biological environment. Non-cytotoxic concentrations to seven different cell lines, including tumorigenic and non-tumorigenic cells, were determined by standard 2D in vitro assays. Gold concentrations ≤ 2.4 mg L-1 (16.5 nM AuNPs) were non-cytotoxic and therefore chosen for further analyses. Cells exposed to GA-AuNPs were uptaken by melanoma cells through endocytic processes. Next we described remarkable biological properties using non-cytotoxic concentrations of this nanomaterial. Invasion through an extracellular matrix barrier as well as 3D growth capacity (anchorage-independent colony formation and spheroids growth) were negatively affected by 2.4 mg L-1 GA-AuNPs. Additionally, exposed spheroids showed morphological changes, suggesting that GA-AuNPs could penetrate into the preformed tumor and affect its integrity. All together these results demonstrate that side effects, such as cytotoxicity, can be avoided by choosing the right concentration, nevertheless, preserving desirable effects such as modulation of key tumor cell malignancy features.
Subject(s)
Antineoplastic Agents/pharmacology , Cell Movement/drug effects , Gold Compounds/pharmacology , Melanoma, Experimental/drug therapy , Metal Nanoparticles , Skin Neoplasms/drug therapy , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/metabolism , Antineoplastic Agents/toxicity , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Stability , Endocytosis , Gold Compounds/chemistry , Gold Compounds/metabolism , Gold Compounds/toxicity , Gum Arabic/chemistry , Humans , Melanoma, Experimental/metabolism , Melanoma, Experimental/pathology , Metal Nanoparticles/chemistry , Metal Nanoparticles/toxicity , Mice , Nanomedicine , Neoplasm Invasiveness , Neoplasm Metastasis , Particle Size , Skin Neoplasms/metabolism , Skin Neoplasms/pathologyABSTRACT
[This corrects the article DOI: 10.1039/C5RA24858B.].
