Abstract
Mesoporous silica particles (MSP) are major candidates for drug delivery systems due to their versatile, safe, and controllable nature. Understanding their intracellular route and biodegradation process is a challenge, especially when considering their use in neuronal repair. Here, we characterize the spatiotemporal intracellular destination and degradation pathways of MSP upon endocytosis by HeLa cells and NSC-34 motor neurons using confocal and electron microscopy imaging together with inductively-coupled plasma optical emission spectroscopy analysis. We demonstrate how MSP are captured by receptor-mediated endocytosis and are temporarily stored in endo-lysosomes before being finally exocytosed. We also illustrate how particles are often re-endocytosed after undergoing surface erosion extracellularly. On the other hand, silica particles engineered to target the cytosol with a carbon nanotube coating, are safely dissolved intracellularly in a time scale of hours. These studies provide fundamental clues for programming the sub-cellular fate of MSP and reveal critical aspects to improve delivery strategies and to favor MSP safe elimination. We also demonstrate how the cytosol is significantly more corrosive than lysosomes for MSP and show how their biodegradation is fully biocompatible, thus, validating their use as nanocarriers for nervous system cells, including motor neurons.
Highlights
The success of nanotechnology applied in health requires the use of materials with well-defined in vivo functionalities
Given the lack of information regarding the precise sequential steps in the intracellular processing of Mesoporous silica particles (MSP), here we investigate in detail the sub-cellular route and the interplay between the design of silica particle carriers and their degradation inside cells
The MSP core displays a diameter of ca. 500 nm with mesopores of 2.5 to 3.5 nm
Summary
The success of nanotechnology applied in health requires the use of materials with well-defined in vivo functionalities. Understanding the biocompatibility, intracellular destination, biodegradation and elimination routes of nanomaterials are critical issues. Nanomaterial biodegradation is not the main issue in cancer treatment. The high proliferation rate of the tumoral and peritumoral cells results in a progressive reduction of the nanomaterial loaded per cell to tolerable amounts [1,2,3]. Identifying the cellular compartment where nanomaterials are degraded and accumulate can serve to control/predict spatiotemporally the release of the therapeutic compound and to customize nanoparticles ad hoc, preserving some therapeutic agents from early degradation in hostile cellular environments, i.e., the lysosomes [5,6]. There are no standards for a fully comprehensive and reliable characterization of the diversity and complexity of nanomaterials, or protocols to predict the interaction of these or their degradation products, with proteins, cells, and tissues [7]
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