Hype vs. Health: How Approved Nanomedicines Have Met (or Missed) Early Predictions.

Two decades after the first bold proclamations that nanomedicine would deliver "magic-bullet" therapies capable of cell-level targeting, the field stands at a crossroads. While some initial promises (improved delivery of poorly water-soluble drugs and enhanced efficacy and biocompatibility of nano-based devices) have been fulfilled, other early promises (active targeting, biodegradability, multifunctionality, triggered responses, real-time data output, and implantable sensors) remain only partially realized. This article will compare the properties of approved nano-based products to those of the ideal products, assess the shortcomings of existing nano-based products, and discuss critical issues in nanotoxicity (biodistribution and protein corona effects, immune interactions, and biopersistence) and the lack of data on product and end-of-life life cycle analyses. The role of in silico tools in the various steps of nanodrug and nano-based device development and manufacturing-areas in which these tools are the most established (nanocarrier design, prediction of cellular effects, chemical composition optimization, manufacturing, and signal interpretation)-is also addressed. Future goals include biodegradable targeted delivery systems, better tissue integration of implants, and implantable sensors. It is expected that, alongside careful physicochemical characterization of the nanoproduct, toxicity testing focused on nano-specific effects and life cycle analyses of production and end-of-life phases will facilitate the approval of nano-based products.