Leveraging self-assembled nanobiomaterials for improved cancer immunotherapy.

Nanomaterials and targeted drug delivery vehicles improve the therapeutic index of drugs and permit greater control over their pharmacokinetics, biodistribution, and bioavailability. Here, nanotechnologies applied to cancer immunotherapy are discussed with a focus on current and next generation self-assembling drug delivery systems composed of lipids and/or polymers. Topics covered include the fundamental design, suitability, and inherent properties of nanomaterials that induce anti-tumor immune responses and support anti-cancer vaccination. Established active and passive targeting strategies as well as newer "indirect" methods are presented together with insights into how nanocarrier structure and surface chemistry can be leveraged for controlled delivery to the tumor microenvironment while minimizing off-target effects.

Surface chemistry-mediated modulation of adsorbed albumin folding state specifies nanocarrier clearance by distinct macrophage subsets.

Controlling nanocarrier interactions with the immune system requires a thorough understanding of the surface properties that modulate protein adsorption in biological fluids, since the resulting protein corona redefines cellular interactions with nanocarrier surfaces. Albumin is initially one of the dominant proteins to adsorb to nanocarrier surfaces, a process that is considered benign or beneficial by minimizing opsonization or inflammation. Here, we demonstrate the surface chemistry of a model nanocarrier can be engineered to stabilize or denature the three-dimensional conformation of adsorbed albumin, which respectively promotes evasion or non-specific clearance in vivo. Interestingly, certain common chemistries that have long been considered to convey stealth properties denature albumin to promote nanocarrier recognition by macrophage class A1 scavenger receptors, providing a means for their eventual removal from systemic circulation. We establish that the surface chemistry of nanocarriers can be specified to modulate adsorbed albumin structure and thereby tune clearance by macrophage scavenger receptors.