Functionalization of protein-based nanocages for drug delivery applications

Schoonen, Lise; Hest, Jan C. M. van

doi:10.1039/c4nr00915k

Cited by 161 publications

(138 citation statements)

References 196 publications

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“…By providing a protective shell for molecular cargo, these nanostructures serve as multipurpose containers for the transport of viral payloads1, biomineralization2, protein folding3 and degradation4, enzyme encapsulation56 and even catalysis of short metabolic sequences78. Inspired by this precedent, protein cages are being engineered in the laboratory as customized nanoreactors910, delivery or display vehicles11 and artificial organelles1213 for diverse applications in medicine, materials science and synthetic biology.…”

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confidence: 99%

Structure and assembly of scalable porous protein cages

et al. 2017

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Proteins that self-assemble into regular shell-like polyhedra are useful, both in nature and in the laboratory, as molecular containers. Here we describe cryo-electron microscopy (EM) structures of two versatile encapsulation systems that exploit engineered electrostatic interactions for cargo loading. We show that increasing the number of negative charges on the lumenal surface of lumazine synthase, a protein that naturally assembles into a ∼1-MDa dodecahedron composed of 12 pentamers, induces stepwise expansion of the native protein shell, giving rise to thermostable ∼3-MDa and ∼6-MDa assemblies containing 180 and 360 subunits, respectively. Remarkably, these expanded particles assume unprecedented tetrahedrally and icosahedrally symmetric structures constructed entirely from pentameric units. Large keyhole-shaped pores in the shell, not present in the wild-type capsid, enable diffusion-limited encapsulation of complementarily charged guests. The structures of these supercharged assemblies demonstrate how programmed electrostatic effects can be effectively harnessed to tailor the architecture and properties of protein cages.

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confidence: 99%

Structure and assembly of scalable porous protein cages

et al. 2017

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“…Fts are small enough to penetrate capillary spaces and large enough to avoid renal clearance. Notably, Fts are physiological materials, very soluble in aqueous solutions and in the blood, with low toxicity, susceptible to chemical modifications and being modified by molecular biology techniques [3][4][5][6][7][8][9][10]. Materials such as Fe 3 O 4 , Co 3 O 4 , Mn 3 O 4 , Pt, CoPt, Pd, CdS, CdSe, ZnSe, CaCO 3 , SrCO 3 , Au, Ag and BaCO 3 have been produced and characterized in different ferritin templates [11].…”

Section: Introductionmentioning

confidence: 99%

Use of Ferritin-Based Metal-Encapsulated Nanocarriers as Anticancer Agents

et al. 2017

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Abstract:The ability of ferritin to bind and deliver metals and metal-based drugs to human neuroblastoma SH-SY5Y cells was studied. We used heavy chain (H) ferritin-based metal-containing nanocarriers to test whether these constructs, which are able to cross the blood-brain barrier, may be used for the delivery of toxic molecules to brain cells, and to study their effect on the viability and cellular redox homeostasis of human neuroblastoma cells. We show that metal-containing nanocarriers are efficiently captured by SH-SY5Y cells. Iron-containing nanocarriers have a proliferative effect, while silver and cisplatin-encapsulated nanocarriers determine concentration-dependent neuroblastoma cell death. This work is a proof of concept for the use of ferritins for the delivery of toxic molecules to brain tumors.

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“…PNPs are found in a broad range of living organisms from microorganism such as virus and bacteria to human and have highly diverse structural characteristics in terms of size, shape, assembly pattern, and surface topology 41, 42. Each type of PNP is biosynthesized inside cells through its own self‐assembly pattern, which always enables nanoparticle synthesis in a highly reproducible manner.…”

Section: Resultsmentioning

confidence: 99%

Nonimmunogenetic Viral Capsid Carrier with Cancer Targeting Activity

Lee

Yoon

et al. 2018

Advanced Science

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Although protein nanoparticles (PNPs) (e.g., viral capsids) capable of delivering a broad range of drug agents have shown distinctive advantages over synthetic nanomaterials, PNPs have an intrinsic drawback that hampers their clinical application, that is, potential immunogenicity. Here, a novel method for resolving the immunogenicity problem of PNPs, which is based on the genetic presentation of albumin‐binding peptides (ABPs) on the surface of PNP, is reported. ABPs are inserted into the surface of a viral capsid (hepatitis B virus capsid/HBVC) while preserving the native self‐assembly function of HBVC. The ABPs effectively gather human serum albumins around HBVC and significantly reduce both inflammatory response and immunoglobulin titer in live mice compared to ABP‐free HBVC. Furthermore, ABP‐conjugated HBVCs remain within tumors for a longer period than HBVCs conjugated to tumor cell receptor‐bindingpeptides, indicating that the ABPs are also capable of enhancing tumor‐targeting performance. Although applied to HBVC for proof of concept, this novel approach may provide a general platform for resolving immunogenicity and cancer‐targeting problems of PNPs, which enables the development of a variety of PNP‐based drug delivery carriers with high safety and efficacy.

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Functionalization of protein-based nanocages for drug delivery applications

Cited by 161 publications

References 196 publications

Structure and assembly of scalable porous protein cages

Structure and assembly of scalable porous protein cages

Use of Ferritin-Based Metal-Encapsulated Nanocarriers as Anticancer Agents

Nonimmunogenetic Viral Capsid Carrier with Cancer Targeting Activity

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