Silica-Based Nanoparticles for Biomedical Applications: From Nanocarriers to Biomodulators

• Published in: Accounts of chemical research 2020-08, Vol.53 (8), p.1545-1556
• Main Authors: Yang, Yannan, Zhang, Min, Song, Hao, Yu, Chengzhong
• Format: Article
• Language: English
• ISSN: 0001-4842; 1520-4898
• DOI: 10.1021/acs.accounts.0c00280

Conspectus Silica-based nanoparticles (SNPs) are a classic type of material employed in biomedical applications because of their excellent biocompatibility and tailorable physiochemical properties. Typically, SNPs are designed as nanocarriers for therapeutics delivery, which can address a number of intrinsic drawbacks of therapeutics, including limited bioavailability, short circulation lifetime, and unfavorable biodistribution. To improve the delivery efficiency and spatiotemporal precision, tremendous efforts have been devoted to engineering the physiochemical properties of SNPs, including particle size, morphology, and mesostructure, as well as conjugating targeting ligands and/or “gatekeepers” to endow improved cell selectivity and on demand release profiles. Despite significant progress, the biologically inert nature of the bare silica framework has largely restricted the functionalities of SNPs, rendering conventional SNPs mainly as nanocarriers for targeted delivery and controlled release. To meet the requirements of next generation nanomedicines with improved efficacy and precision, new insights on the relationship between the physiochemical properties of SNPs and their biological behavior are highly valuable. Meanwhile, a conceptual shift from a simple spatiotemporal control mechanism to a more sophisticated biochemistry and signaling pathway modulation would be of great importance. In this Account, an overview of our recent contribution to the field is presented, wherein SNPs with rationally designed nanostructures and nanochemistry are applied as nanocarriers (defined as “nanomaterials being used as a transport module for another substance” according to Wikipedia) and/or biomodulators (defined as “any material that modifies a biological response” according to Wiktionary). This Account encompasses two main sections. In the first section, we focus on the conventional nanocarriers concept with new insights on the design principles of the nanostructures. We present examples to demonstrate the engineering of pore geometry, surface topology, and asymmetry of nanoparticles to achieve enhanced drug, gene, and protein delivery efficiency. The contribution of surface roughness of SNPs on improving the cellular uptake efficiency, adhesion property, and DNA transfection capacity is particularly highlighted. In the second section, we discuss novel SNPs designed as biomodulators to regulate intracellular microenvironment and cell signaling, such as the oxidat