Rational design of fiber forming supramolecular structures

Kumar, Vivek; Wang, Benjamin K.; Kanahara, Satoko M.

doi:10.1177/1535370216640941

Cited by 28 publications

(25 citation statements)

References 160 publications

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“…Employing molecular conformations to form higher‐order structures and undergo changes responding to subtle perturbations in their environmental cues is ubiquitous in biopolymers such as collagen, nucleic acids. Given the unique functionalities such systems offer, extensive research has been dedicated to developing man‐made macromolecules with similar functions . Polymer hydrogels, cross‐linked network of macromolecules, that undergo reversible phase transitions in response to subtle changes in their environment are one of the early examples of such systems .…”

Section: Introductionmentioning

confidence: 99%

“…Given the unique functionalities such systems offer, extensive research has been dedicated to developing man-made macromolecules with similar functions. [1][2][3][4][5] Polymer hydrogels, cross-linked network of macromolecules, that undergo reversible phase transitions in response to subtle changes in their environment are one of the early examples of such systems. [6,7] The stimuli-responsive hydrogels exhibit volume/phase transitions responding to external and internal triggers such as temperature, pH, electric field, A variety of macrocyclic molecules and their derivatives such as cyclodextrins (CDs), cucurbit[n]urils (CBs), calixarenes (CAs), crown ethers, and pillar[n]arenes have been utilized as hosts to create supramolecular structures in the presence of a guest molecule through molecular recognition.…”

Section: Introductionmentioning

confidence: 99%

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Stimuli‐Responsive Supramolecular Hydrogels and Their Applications in Regenerative Medicine

Hoque

Sangaj

Varghese

2018

Macromolecular Bioscience

144

108

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Supramolecular hydrogels are a class of self-assembled network structures formed via non-covalent interactions of the hydrogelators. These hydrogels capable of responding to external stimuli are considered to be smart materials due to their ability to undergo sol–gel and/or gel–sol transition upon subtle changes in their surroundings. Such stimuli-responsive hydrogels are intriguing biomaterials with applications in tissue engineering, delivery of cells and drugs, modulating tissue environment to promote innate tissue repair, and imaging for medical diagnostics among others. This review summarizes the recent developments in stimuli-responsive supramolecular hydrogels and their potential applications in regenerative medicine. Specifically, various structural aspects of supramolecular hydrogelators involved in self-assembly, the role of external stimuli in tuning/controlling their phase transitions, and how these functions could be harnessed to advance applications in regenerative medicine are focused on. Finally, the key challenges and future prospects for these versatile materials are briefly described.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Stimuli‐Responsive Supramolecular Hydrogels and Their Applications in Regenerative Medicine

Hoque

Sangaj

Varghese

2018

Macromolecular Bioscience

144

108

View full text Add to dashboard Cite

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“…Proteins and peptides, over other materials commonly explored as drug delivery systems, offer high structural and functional versatility easily regulatable by genetic engineering. This flexibility allows generating protein materials non-existing in nature, with novel functions or combinations of them, for appealing applications [2][3][4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Controlling self-assembling and tumor cell-targeting of protein-only nanoparticles through modular protein engineering

et al. 2019

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Modular protein engineering is suited to recruit complex and multiple functionalities in single-chain polypeptides. Although still unexplored in a systematic way, it is anticipated that the positioning of functional domains would impact and refine these activities, including the ability to organize as supramolecular entities and to generate multifunctional protein materials. To explore this concept, we have repositioned functional segments in the modular protein T22-GFP-H6 and characterized the resulting alternative fusions. In T22-GFP-H6, the combination of T22 and H6 promotes selfassembling as regular nanoparticles and selective binding and internalization of this material in CXCR4-overexpressing tumor cells, making them appealing as vehicles for selective drug delivery. The results show that the pleiotropic activities are dramatically affected in module-swapped constructs, proving the need of a carboxy terminal positioning of H6 for protein self-assembling, and the accommodation of T22 at the amino terminus as a requisite for CXCR4 + cell binding and internalization. Furthermore, the failure of self-assembling as regular oligomers reduces cellular penetrability of the fusions while keeping the specificity of the T22-CXCR4 interaction. All these data instruct how multifunctional nanoscale protein carriers can be designed for smart, protein-driven drug delivery, not only for the treatment of CXCR4 + human neoplasias, but also for the development of anti-HIV drugs and other pathologies in which CXCR4 is a relevant homing marker.

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“…Proteins are versatile macromolecules whose structures and functional capabilities can be tailored by conventional genetic engineering. Among other regulatable properties, self-assembling can be achieved and controlled by protein engineering [1][2][3][4][5][6][7][8][9][10][11][12]. By either peptide synthesis or recombinant DNA technologies, diverse categories of soft structures, including hydrogels, fibers, layers and nanoparticles can be fabricated [13,14].…”

Section: Introductionmentioning

confidence: 99%

Endosomal escape of protein nanoparticles engineered through humanized histidine-rich peptides

et al. 2019

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Poly-histidine peptides such as H6 (HHHHHH) are used in protein biotechnologies as purification tags, protein-assembling agents and endosomal-escape entities. The pleiotropic properties of such peptides make them appealing to design protein-based smart materials or nanoparticles for imaging or drug delivery to be produced in form of recombinant proteins. However, the clinical applicability of H6tagged proteins is restricted by the potential immunogenicity of these segments. In this study, we have explored several humanized histidine-rich peptides in tumor-targeted modular proteins, which can specifically bind and be internalized by the target cells through the tumoral marker CXCR4. We were particularly interested in exploring how protein purification, self-assembling and endosomal escape perform in proteins containing the variant histidine-rich tags. Among the tested candidates, the peptide H5E (HEHEHEHEH) is promising as a good promoter of endosomal escape of the associated fulllength protein upon endosomal internalization. The numerical modelling of cell penetration and endosomal escape of the tested proteins has revealed a negative relationship between the amount of protein internalized into target cells and the efficiency of cytoplasmic release. This fact demonstrates that the His-mediated, proton sponge-based endosomal escape saturates at moderate amounts of internalized protein, a fact that might be critical for the design of protein materials for cytosolic molecular delivery.

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Rational design of fiber forming supramolecular structures

Cited by 28 publications

References 160 publications

Stimuli‐Responsive Supramolecular Hydrogels and Their Applications in Regenerative Medicine

Stimuli‐Responsive Supramolecular Hydrogels and Their Applications in Regenerative Medicine

Controlling self-assembling and tumor cell-targeting of protein-only nanoparticles through modular protein engineering

Endosomal escape of protein nanoparticles engineered through humanized histidine-rich peptides

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