EGFR Ligand Clustering on E2 Bionanoparticles for Targeted Delivery of Chemotherapeutics to Breast Cancer Cells.

Naturally occurring protein nanocages are promising drug carriers because of their uniform size and biocompatibility. Engineering efforts have enhanced the delivery properties of nanocages, but cell specificity and high drug loading remain major challenges. Herein, we fused the SpyTag peptide to the surface of engineered E2 nanocages to enable tunable nanocage decoration and effective E2 cell targeting using a variety of SpyCatcher (SC) fusion proteins.

Incorporation of Endosomolytic Peptides with Varying Disruption Mechanisms into EGFR-Targeted Protein Conjugates: The Effect on Intracellular Protein Delivery and EGFR Specificity in Breast Cancer Cells.

Intracellular delivery of protein therapeutics remains a significant challenge limiting the majority of clinically available protein drugs to extracellular targets. Strategies to deliver proteins to subcellular compartments have traditionally relied on cell-penetrating peptides, which can drive enhanced internalization but exhibit unreliable activity and are rarely able to target specific cells, leading to off-target effects. Moreover, few design rules exist regarding the relative efficacy of various endosomal escape strategies in proteins.

Engineering bionanoparticles for improved biosensing and bioimaging.

The importance of bioimaging and biosensing has been clear with the onset of the COVID-19 pandemic. In addition to viral detection, detection of tumors, glucose levels, and microbes is necessary for improved disease treatment and prevention. Bionanoparticles, such as extracellular vesicles and protein nanoparticles, are ideal platforms for biosensing and bioimaging applications because of their propensity for high density surface functionalization and large loading capacity.

Site-Specific Bioconjugation Approaches for Enhanced Delivery of Protein Therapeutics and Protein Drug Carriers.

Proteins have the capacity to treat a multitude of diseases both as therapeutics and as drug carriers due to their complex functional properties, specificity toward binding partners, biocompatibility, and programmability. Despite this, native proteins often require assistance to target diseased tissue due to poor pharmacokinetic properties and membrane impermeability. Functionalizing therapeutic proteins and drug carriers through direct conjugation of delivery moieties can enhance delivery capabilities.

Modular Hepatitis B Virus-like Particle Platform for Biosensing and Drug Delivery.

The hepatitis B virus-like particle (HBV VLP) is an attractive protein nanoparticle platform due to the availability of 240 modification sites for engineering purposes. Although direct protein insertion into the surface loop has been demonstrated, this decoration strategy is restricted by the size of the inserted protein moieties. Meanwhile, larger proteins can be decorated using chemical conjugations; yet these approaches perturb the integrity of more delicate proteins and can unfavorably orient the proteins, impairing active surface display.