Strategies to assemble therapeutic and imaging molecules into inorganic nanocarriers

Inorganic nanocarriers are potent candidates for delivering conventional anticancer drugs, nucleic acid-based therapeutics, and imaging agents, influencing their blood half-lives, tumor targetability, and bioactivity. In addition to the high surface area-to-volume ratio, they exhibit excellent scalability in synthesis, controllable shape and size, facile surface modification, inertness, stability, and unique optical and magnetic properties. However, only a limited number of inorganic nanocarriers have been so far approved for clinical applications due to burst drug release, poor target specificity, and toxicity. To overcome these barriers, understanding the principles involved in loading therapeutic and imaging molecules into these nanoparticles (NPs) and the strategies employed in enhancing sustainability and targetability of the resultant complexes and ensuring the release of the payloads in extracellular and intracellular compartments of the target site is of paramount importance. Therefore, we will shed light on various loading mechanisms harnessed for different inorganic NPs, particularly involving physical entrapment into porous/hollow nanostructures, ionic interactions with native and surface-modified NPs, covalent bonding to surface-functionalized nanomaterials, hydrophobic binding, affinity-based interactions, and intercalation through co-precipitation or anion exchange reaction.