The Nano–Bio Interactions of Nanomedicines: Understanding the Biochemical Driving Forces and Redox Reactions

Abstract

CONSPECTUS: Engineered nanomaterials (ENMs) have been developed for imaging, drug delivery, diagnosis, and clinical therapeutic purposes because of their outstanding physicochemical characteristics. However, the function and ultimate efficiency of nanomedicines remain unsatisfactory for clinical application, mainly because of our insufficient understanding of nanomaterial/nanomedicine−biology (nano−bio) interactions. The nonequilibrated, complex, and heterogeneous nature of the biological milieu inevitably influences the dynamic bioidentity of nanoformulations at each site (i.e., the interfaces at different biological fluids (biofluids), environments, or biological structures) of nano−bio interactions. The continuous interplay between a nanomedicine and the biological molecules and structures in the biological environments can, for example, affect cellular uptake or completely alter the designed function of the nanomedicine. Accordingly, the weak and strong driving forces at the nano−bio interface may elicit structural reconformation, decrease bioactivity, and induce dysfunction of the nanomaterial and/or redox reactions with biological molecules, all of which may elicit unintended and unexpected biological outcomes. In contrast, these driving forces also can be manipulated to mitigate the toxicity of ENMs or improve the targeting abilities of ENMs. Therefore, a comprehensive understanding of the underlying mechanisms of nano−bio interactions is paramount for the intelligent design of safe and effective nanomedicines. In this Account, we summarize our recent progress in probing the nano−bio interaction of nanomedicines, focusing on the driving force and redox reaction at the nano−bio interface, which have been recognized as the main factors that regulate the functions and toxicities of nanomedicines. First, we provide insight into the driving force that shapes the boundary of different nano−bio interfaces (including proteins, cell membranes, and biofluids), for instance, hydrophobic, electrostatic, hydrogen bond, molecular recognition, metal-coordinate, and stereoselective interactions that influence the different nano−bio interactions at each contact site in the biological environment. The physicochemical properties of both the nanoparticle and the biomolecule are varied, causing structure recombination, dysfunction, and bioactivity loss of proteins; correspondingly, the surface properties, biological functions, intracellular uptake pathways, and fate of ENMs are also influenced. Second, with the help of these driving forces, four kinds of redox interactions with reactive oxygen species (ROS), antioxidant, sorbate, and the prosthetic group of oxidoreductases are utilized to regulate the intracellular redox equilibrium and construct synergetic nanomedicines for combating bacteria and cancers. Three kinds of electron-transfer mechanisms are involved in designing nanomedicines, including direct electron injection, sorbate-mediated, and irradiation-induced processes. Finally, we discuss the factors that influence th...

The Role of Branch Cell Symmetry and Other Critical Nanoscale Design Parameters in the Determination of Dendrimer Encapsulation Properties

“…This early hypothesis invoked at least three of the six CNDPs that are now known to define and influence those important nano-interfacial interactions between nanoparticles and biological substrates [178]. More recently, Chen et al [182] have reviewed the important role that nanoparticle CNDPs play in the nano-bio interactions of nanomedicines as outlined in Figure 42. It is now widely recognized [180,[183][184][185] that all physico-chemical properties of dendrimers and other well-defined nanoparticles are strictly controlled by six nanoscale design parameters (CNDPs); namely: (1) size, (2) shape, (3) surface chemistry, (4) flexibility/rigidity, (5) architecture and (6) elemental composition.…”

“…Main driving factors (i.e., CNDPs) at the nano-bio interface of a nanoparticle influencing development of nanomedcines. Reproduced with permission from[182]. Copyright 2019 American Chemical Society.…”

Molecular Mechanisms, Characterization Methods, and Utilities of Nanoparticle Biotransformation in Nanosafety Assessments

“…The change of ENMs at nano-bio interfaces is known as biotransformation, which is a result of a myriad of physical and chemical interactions, such as hydrogen bond, hydrophobic, π-π stacking, and electrostatic force between NPs and biomolecules/chemicals. [33,45] Although the nano-bio interfaces have been highly underlined in a recent review, [46] the transportation information regarding ENM uptake in different exposure routes is lack of a comprehensive summary. Biological transformation, such as dissolution, [47][48][49] aggregation and agglomeration, [50,51] or corona formation [52] at nano-bio interfaces, may greatly alter the physicochemical properties of NPs, and then influence cellular signaling pathways, immune system recognition as well as in vivo clearance.…”

Safety Considerations of Cancer Nanomedicine—A Key Step toward Translation

“…The smart design and manufacture of engineered nanomaterials (NMs) is a major scientific achievement that impacts multiple areas, including biomedical and pharmaceutical fields in both research and industry. [1][2][3][4][5][6][7][8] Safety assessment is an integral…”

“…component of any new technology or pharmaceutical product, and nanoenabled products are no exception. [5,[9][10][11][12][13] This notion is in agreement with a US Food and Drug Administration (FDA) draft guideline "Drug Products, Including Biological Products that Contain Nanomaterials Guidance for Industry," which includes statements such as, "FDA does not address, or presuppose, what ultimate regulatory outcome, if any, will result for a particular drug product that contains nanomaterials;" and, "Current [FDA] guidance documents and requirements for the evaluation and maintenance of quality, safety, and efficacy, apply to drug products containing nanomaterials." [14] From a safety perspective, important considerations for biomedical NMs should include the complexity of NM structure, the mechanism by which NMs' physicochemical properties impact biological effects in the clinical setting, physical/ chemical stability, etc.…”