Physiology, pathology and the biomolecular corona: the confounding factors in nanomedicine design

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Abstract

Nanomedicines can acquire different biomolecular coronas from various biological contexts. This review offers a practical guide to tuning corona content to match physiological requirements as a necessary step for future nanomedicine success.

Abstract

The biomolecular corona that forms on nanomedicines in different physiological and pathological environments confers a new biological identity. How the recipient biological system's state can potentially affect nanomedicine corona formation, and how this can be modulated, remains obscure. With this perspective, this review summarizes the current knowledge about the content of biological fluids in various compartments and how they can be affected by pathological states, thus impacting biomolecular corona formation. The content of representative biological fluids is explored, and the urgency of integrating corona formation, as an essential component of nanomedicine designs for effective cargo delivery, is highlighted.

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Michael J. Mitchell, Margaret M. Billingsley, Rebecca M. Haley … (2020)

In recent years, the development of nanoparticles has expanded into a broad range of clinical applications. Nanoparticles have been developed to overcome the limitations of free therapeutics and navigate biological barriers — systemic, microenvironmental and cellular — that are heterogeneous across patient populations and diseases. Overcoming this patient heterogeneity has also been accomplished through precision therapeutics, in which personalized interventions have enhanced therapeutic efficacy. However, nanoparticle development continues to focus on optimizing delivery platforms with a one-size-fits-all solution. As lipid-based, polymeric and inorganic nanoparticles are engineered in increasingly specified ways, they can begin to be optimized for drug delivery in a more personalized manner, entering the era of precision medicine. In this Review, we discuss advanced nanoparticle designs utilized in both non-personalized and precision applications that could be applied to improve precision therapies. We focus on advances in nanoparticle design that overcome heterogeneous barriers to delivery, arguing that intelligent nanoparticle design can improve efficacy in general delivery applications while enabling tailored designs for precision applications, thereby ultimately improving patient outcome overall.

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Principles of nanoparticle design for overcoming biological barriers to drug delivery.

Elvin Blanco, Haifa Shen, Mauro Ferrari (2015)

Biological barriers to drug transport prevent successful accumulation of nanotherapeutics specifically at diseased sites, limiting efficacious responses in disease processes ranging from cancer to inflammation. Although substantial research efforts have aimed to incorporate multiple functionalities and moieties within the overall nanoparticle design, many of these strategies fail to adequately address these barriers. Obstacles, such as nonspecific distribution and inadequate accumulation of therapeutics, remain formidable challenges to drug developers. A reimagining of conventional nanoparticles is needed to successfully negotiate these impediments to drug delivery. Site-specific delivery of therapeutics will remain a distant reality unless nanocarrier design takes into account the majority, if not all, of the biological barriers that a particle encounters upon intravenous administration. By successively addressing each of these barriers, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery.