However, contrary to studies reporting the formation of a multilayer PC, 14–16 other studies have demonstrated the formation of a monolayer PC. The soft corona is composed of loosely bound proteins that attach to the hard corona. 13 The hard corona is the inner-most layer and has proteins that bind more tightly.
#Lipid corona meaning Pc
Often, the PC is subdivided into two segments, hard and soft coronas. 11,12 This occurs due to the high concentration and wide number of freely diffused proteins in the body. A PC is the layers of proteins that adsorb onto the NP after administration. 10 One important, yet often overlooked factor that governs NP success is the role of the protein corona (PC). As with therapeutics, NP complications are often a result of biological barriers, and their successful translation to clinics heavily depends on controlling in vivo factors affecting biodistribution, blood residence, and targeting specific tissues and cells. 9 Additionally, NPs can lower the bioavailability and efficacy of a drug, especially as the drug can become trapped in the particle. 8 This includes their own intrinsic toxicity, complexity, and the lack of one-size-fits-all NPs, the latter meaning that most therapeutics must have their own tailored drug delivery vehicle. The amalgamation of nanotechnology and drug discovery has produced several FDA-approved therapies however, NPs have several obstacles that have prevented their broader utilization. 6 More recent examples include the COVID-19 vaccines, Spikevax and Comirnaty, which are lipid nanoparticle formulations that encapsulate spike protein mRNA.
5 The first FDA-approved nanocarrier–drug combination is Doxil, a liposomal formulation of doxorubicin that received approval in 1995 for the treatment of a variety of cancers. 4 NPs offer more favorable pharmacokinetics while still preserving the intrinsic structure of the drug. Since modulating the chemical structure of a drug can result in lower efficacy, researchers and clinicians have turned to nanoparticles (NPs), which are nano- or micro-sized vehicles that protect and deliver the desired therapeutic. 3 Hydrophobic drug candidates suffer from poor bioavailability while biological therapeutics such as proteins and nucleic acids are rapidly degraded. 1,2 A major cause of this failure is the incompatibility of many therapeutics with the anatomy and physiology of the human body. Unfortunately, most drugs fail to reach government approval due to poor efficacy and toxicity. Introduction Decades of intense drug discovery research have yielded a plethora of potent therapeutics for a variety of diseases. The review concludes with a perspective on the remaining challenges and unexplored areas at the interface of PC and NP research. This is followed by a discussion on the instances in which the conformation of adsorbed proteins can be leveraged for therapeutic purposes, such as controlling protein conformation in assembled matrices in tissue, as well as controlling the PC conformation for modulating immune responses. Then, four types of NPs with extensive utility in biomedical applications are described in greater detail, focusing on the conformation and orientation of adsorbed proteins. This review introduces the main biological factors affecting the conformation of proteins associated with the PC. As a result, this can alter the downstream functionality of the NPs. Since the function of a protein is closely connected to its folded structure, slight differences in the surrounding environment as well as the surface characteristics of the NP materials may cause proteins to lose or gain a function. Therefore, biological factors and protein–NP-interactions can induce changes in the conformation and orientation of proteins in vivo. Additionally, the conformation of proteins is sensitive to their physical and chemical surroundings. The PC has the potential to endow NPs with a new identity and alter their bioactivity, stability, and destination. When introduced into physiological fluids, NPs are coated by proteins, forming a protein corona (PC). However, despite the clinical success of NP technology, it is not well-understood how NPs fundamentally change in biological environments. Nanoparticle (NP)-based therapeutics have ushered in a new era in translational medicine.
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