Biomedical Applications of Supramolecular Systems Based on Host–Guest Interactions

Ma, Xueli; Zhao, Yanli

doi:10.1021/cr500392w

Cited by 998 publications

(750 citation statements)

References 380 publications

(690 reference statements)

Supporting

Mentioning

738

Contrasting

Unclassified

Order By: Relevance

“…This method stands in contrast to similar approaches to covalently graft the same polymer onto the protein, instead offering a broadly useful and modular formulation excipient that can be combined with authentic unmodified protein drugs to extend shelf life. host-guest binding involving cyclodextrin, one of the most commonly used supramolecular hosts in pharmaceutical practice, has a maximum observed affinity for any guest of ∼10 4 M −1 (20). Should even higher CB [7] binding affinities be desired than are possible with binding to native amino acids, prosthetic moieties could be added to proteins to achieve binding with K eq upward of 10 10 to 10 15 M −1 (21)(22)(23).…”

Section: Significancementioning

confidence: 99%

Supramolecular PEGylation of biopharmaceuticals

Webber

Appel

Vinciguerra

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

179

256

View full text Add to dashboard Cite

The covalent modification of therapeutic biomolecules has been broadly explored, leading to a number of clinically approved modified protein drugs. These modifications are typically intended to address challenges arising in biopharmaceutical practice by promoting improved stability and shelf life of therapeutic proteins in formulation, or modifying pharmacokinetics in the body. Toward these objectives, covalent modification with poly(ethylene glycol) (PEG) has been a common direction. Here, a platform approach to biopharmaceutical modification is described that relies on noncovalent, supramolecular host-guest interactions to endow proteins with prosthetic functionality. Specifically, a series of cucurbit [7]uril (CB [7])-PEG conjugates are shown to substantially increase the stability of three distinct protein drugs in formulation. Leveraging the known and high-affinity interaction between CB [7] and an N-terminal aromatic residue on one specific protein drug, insulin, further results in altering of its pharmacological properties in vivo by extending activity in a manner dependent on molecular weight of the attached PEG chain. Supramolecular modification of therapeutic proteins affords a noncovalent route to modify its properties, improving protein stability and activity as a formulation excipient. Furthermore, this offers a modular approach to append functionality to biopharmaceuticals by noncovalent modification with other molecules or polymers, for applications in formulation or therapy. supramolecular chemistry | protein engineering | drug delivery | protein formulation

show abstract

Section: Significancementioning

confidence: 99%

Supramolecular PEGylation of biopharmaceuticals

Webber

Appel

Vinciguerra

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

179

256

View full text Add to dashboard Cite

show abstract

“…Such responsive materials present a promising utilization potential in molecular delivery, controlled drug release, self-repairing devices, and stimuli-responsive sensors (Figure 2 ). [ 10 ] It will be highly useful if a polymer with removable parts can deliver something to the target site and then be chemically regenerated to function again. Overall, this discovery is a research milestone in the polymer synthesis, where simultaneously controlling the polymer formation with integrated functions through synergistic covalent and supramolecular polymerization becomes true.…”

Section: Resultsmentioning

confidence: 99%

Synergistic Assembly of Covalent and Supramolecular Polymers

Bai

Zhao

2016

Macromol. Rapid Commun.

Self Cite

View full text Add to dashboard Cite

Integrating irreplaceable features of both covalent chemistry and noncovalent interactions into a single entity to maximize the applicability is highly desired. Here, a discovery of this type of hybrid, developed by Stupp and co-workers, is developed, where a synergistic combination of covalent and noncovalent compartments enables them to assemble by each other perfectively. The covalent compartments can grow into polymer chains assisted by a supramolecular compartment. The supramolecular compartments can be reversibly removed and re-formed to reconstitute the hybrid structure. The obtained soft materials can serve as functional platforms for molecular delivery or self-repairing materials.

show abstract

“…Construction of self‐assembled nanomaterials aiming to biomedical applications is attractive ever‐growing interests, including various biosensing/imaging probes, drug delivery systems, tissue engineering materials for the purpose of diagnosis and therapy 1, 2, 3, 4, 5. On demand of precise medicine with sensitive/selective diagnosis and targeting therapy, development of activatable theranostic nanoagents that can undergo an intrinsic evolution upon cell uptake is highly imperative 6, 7, 8, 9.…”

Section: Introductionmentioning

confidence: 99%

Sequentially Programmable and Cellularly Selective Assembly of Fluorescent Polymerized Vesicles for Monitoring Cell Apoptosis

et al. 2017

View full text Add to dashboard Cite

The introduction of controlled self‐assembly into living organisms opens up desired biomedical applications in wide areas including bioimaging/assays, drug delivery, and tissue engineering. Besides the enzyme‐activated examples reported before, controlled self‐assembly under integrated stimuli, especially in the form of sequential input, is unprecedented and ultimately challenging. This study reports a programmable self‐assembling strategy in living cells under sequentially integrated control of both endogenous and exogenous stimuli. Fluorescent polymerized vesicles are constructed by using cholinesterase conversion followed by photopolymerization and thermochromism. Furthermore, as a proof‐of‐principle application, the cell apoptosis involved in the overexpression of cholinesterase in virtue of the generated fluorescence is monitored, showing potential in screening apoptosis‐inducing drugs. The approach exhibits multiple advantages for bioimaging in living cells, including specificity to cholinesterase, red emission, wash free, high signal‐to‐noise ratio.

show abstract

Biomedical Applications of Supramolecular Systems Based on Host–Guest Interactions

Abstract: Figure 5. (a) Directly using the β-CD/PTX complex to form biodegradable capsules. Reprinted with permission from ref 153.

Cited by 998 publications

References 380 publications

Supramolecular PEGylation of biopharmaceuticals

Supramolecular PEGylation of biopharmaceuticals

Synergistic Assembly of Covalent and Supramolecular Polymers

Sequentially Programmable and Cellularly Selective Assembly of Fluorescent Polymerized Vesicles for Monitoring Cell Apoptosis

Contact Info

Product

Resources

About