Caged protein nanoparticles for drug delivery

• Caged proteins can overcome limitations of other nanoparticles for drug delivery.
• Unique physical, chemical, and recombinant methods allow drug loading/release.
• Simultaneously display of drug and targeting molecules can improve drug efficacy.
• Caged proteins are well-suited for immunotherapy because of similarities with viruses.

Caged protein nanoparticles possess many desirable features for drug delivery, such as ideal sizes for endocytosis, non-toxic biodegradability, and the ability to functionalize at three distinct interfaces (external, internal, and inter-subunit) using the tools of protein engineering. Researchers have harnessed these attributes by covalently and non-covalently loading therapeutic molecules through mechanisms that facilitate release within specific microenvironments. Effective delivery depends on several factors, including specific targeting, cell uptake, release kinetics, and systemic clearance. The innate ability of the immune system to recognize and respond to proteins has recently been exploited to deliver therapeutic compounds with these platforms for immunomodulation. The diversity of drugs, loading/release mechanisms, therapeutic targets, and therapeutic efficacy are discussed in this review.

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