Abstract:Multivalent nanoparticles
that target a cell surface receptor that
is overexpressed by cancer cells are a promising delivery system for
cancer therapy. However, the impact of the receptor density and nanoparticle
ligand valency on the cell uptake has not been studied in a system
where both variables can be systematically tuned over a wide range.
To address this lacuna, we report cell-uptake studies on a genetically
engineered breast cancer cell line with tunable ErbB2 expression by
a polypeptide micelle with t… Show more
“…In recent research, to assess the impact of nanoparticle ligand valency and receptor density on cellular internalization, researchers have performed cell uptake studies on ErbB2-targeting, EC1 surface–functionalized micelles at five ligand valencies and 11 receptor densities [ 152 ]. They have reported that receptor density to ligand valency ratio of 0.7–4.5 and a minimum of 1.6 linkages between receptor and ligands are required to initiate cellular internalization.…”
Section: Effective Internalization Of Multivalent Drug Delivery Nanoconstructsmentioning
confidence: 99%
“…Authors have reported that the increment of ligand valence to 40-valent ErbB2 targeting peptides for a 20-nm radius nanoparticle at the ErbB2-medium and ErbB2-high levels potentiated the cellular internalization (Fig. 8 B), suggesting the use of nanocarriers with a higher valency of targeting moiety for effective drug delivery [ 152 ]. Fig.…”
Section: Effective Internalization Of Multivalent Drug Delivery Nanoconstructsmentioning
confidence: 99%
“…A Cellular internalization of micelles as a function of receptor density for different ligand valencies. B Cellular internalization of micelles as a function of ligand valency for MCF-7/Tet-On/ZsGreen-ErbB2 cells at varying doxycycline concentrations (reused from Wang et al [ 152 ] permission with American Chemical Society, Copyright 2020) …”
Section: Effective Internalization Of Multivalent Drug Delivery Nanoconstructsmentioning
Graphical abstract
A century ago, the groundbreaking concept of the magic bullet was given by Paul Ehrlich. Since then, this concept has been extensively explored in various forms to date. The concept of multivalency is among such advancements of the magic bullet concept. Biologically, the concept of multivalency plays a critical role in significantly huge numbers of biochemical interactions. This concept is the sole reason behind the higher affinity of biological molecules like viruses to more selectively target the host cell surface receptors. Multivalent nanoconstructs are a promising approach for drug delivery by the active targeting principle. Designing and developing effective and target-specific multivalent drug delivery nanoconstructs, on the other hand, remain a challenge. The underlying reason for this is a lack of understanding of the crucial interactions between ligands and cell surface receptors, as well as the design of nanoconstructs. This review highlights the need for a better theoretical understanding of the multivalent effect of what happens to the receptor–ligand complex after it has been established. Furthermore, the critical parameters for designing and developing robust multivalent systems have been emphasized. We have also discussed current advances in the design and development of multivalent nanoconstructs for drug delivery. We believe that a thorough knowledge of theoretical concepts and experimental methodologies may transform a brilliant idea into clinical translation.
“…In recent research, to assess the impact of nanoparticle ligand valency and receptor density on cellular internalization, researchers have performed cell uptake studies on ErbB2-targeting, EC1 surface–functionalized micelles at five ligand valencies and 11 receptor densities [ 152 ]. They have reported that receptor density to ligand valency ratio of 0.7–4.5 and a minimum of 1.6 linkages between receptor and ligands are required to initiate cellular internalization.…”
Section: Effective Internalization Of Multivalent Drug Delivery Nanoconstructsmentioning
confidence: 99%
“…Authors have reported that the increment of ligand valence to 40-valent ErbB2 targeting peptides for a 20-nm radius nanoparticle at the ErbB2-medium and ErbB2-high levels potentiated the cellular internalization (Fig. 8 B), suggesting the use of nanocarriers with a higher valency of targeting moiety for effective drug delivery [ 152 ]. Fig.…”
Section: Effective Internalization Of Multivalent Drug Delivery Nanoconstructsmentioning
confidence: 99%
“…A Cellular internalization of micelles as a function of receptor density for different ligand valencies. B Cellular internalization of micelles as a function of ligand valency for MCF-7/Tet-On/ZsGreen-ErbB2 cells at varying doxycycline concentrations (reused from Wang et al [ 152 ] permission with American Chemical Society, Copyright 2020) …”
Section: Effective Internalization Of Multivalent Drug Delivery Nanoconstructsmentioning
Graphical abstract
A century ago, the groundbreaking concept of the magic bullet was given by Paul Ehrlich. Since then, this concept has been extensively explored in various forms to date. The concept of multivalency is among such advancements of the magic bullet concept. Biologically, the concept of multivalency plays a critical role in significantly huge numbers of biochemical interactions. This concept is the sole reason behind the higher affinity of biological molecules like viruses to more selectively target the host cell surface receptors. Multivalent nanoconstructs are a promising approach for drug delivery by the active targeting principle. Designing and developing effective and target-specific multivalent drug delivery nanoconstructs, on the other hand, remain a challenge. The underlying reason for this is a lack of understanding of the crucial interactions between ligands and cell surface receptors, as well as the design of nanoconstructs. This review highlights the need for a better theoretical understanding of the multivalent effect of what happens to the receptor–ligand complex after it has been established. Furthermore, the critical parameters for designing and developing robust multivalent systems have been emphasized. We have also discussed current advances in the design and development of multivalent nanoconstructs for drug delivery. We believe that a thorough knowledge of theoretical concepts and experimental methodologies may transform a brilliant idea into clinical translation.
“…Superselectivity can be applied for targeted delivery to cells with receptors that are not unique but instead are overexpressed compared to other cells. [19][20][21] The receptor density at which the selectivity is highest can be tuned by varying the interaction strength and the architecture of the particle. [22][23][24] The receptor density is directly related to the multivalent binding affinity.…”
Understanding how influenza viruses traverse the mucus and recognize host cells is critical for evaluating their zoonotic potential, and for prevention and treatment of the disease. The surface of the influenza A virus is covered with the receptor‐binding protein hemagglutinin and the receptor‐cleaving enzyme neuraminidase, which jointly control the interactions between the virus and the host cell. These proteins are organized in closely spaced trimers and tetramers to facilitate multivalent interactions with sialic acid‐terminated glycans. This review shows that the individually weak multivalent interactions of influenza viruses allow superselective binding, virus‐induced recruitment of receptors, and the formation of dynamic complexes that facilitate molecular walking. Techniques to measure the avidity and receptor specificity of influenza viruses are reviewed, and the pivotal role of multivalent interactions with their emergent properties in crossing the mucus and entering host cells is discussed. A model is proposed for the initiation of cell entry through virus‐induced receptor clustering. The multivalent interactions of influenza viruses are maintained in a dynamic regime by a functional balance between binding and cleaving.
“…Similarly, ELP micelles of sequence (XGVPG) 40 (SGVPG) 40 (where X is either W or V in a 1:4 ratio) have been modified to display EC1 (WTGWCLNPEESTWGFCTGSF), a targeting and internalization sequence for ErbB2, a tyrosine kinase from the epidermal growth factor receptor family. [184] Multivalent display of EC1 on the surface of these micelles increased their avidity for ErbB2, indicating their potential for targeted drug delivery as ErbB2 is overexpressed in 30% of human breast cancers. [359] Finally, Dzuricky et al [185] Multivalent peptide materials can also be used as biosensors.…”
Self-assembled peptide materials have emerged as promising bioinspired tools for applications that include regenerative medicine, drug delivery, antimicrobial and vaccine development, optics, and catalysis. Peptide self-assembly mediated by noncovalent hydrogen bonding, coulombic, hydrophobic, and aromatic interactions gives rise to a variety of supramolecular structures that reflect on the nature of the constituent peptides. The emergent properties of these supramolecular peptide materials often depend on the multivalent presentation of functional appendages on the self-assembled scaffold. For example, the multivalent display of cell-signaling motifs on self-assembled peptide nanofibrils provides materials that are excellent extracellular matrix mimetics for tissue engineering applications. This review includes a discussion of chemical strategies that address the challenge of appending functional signal motifs in a multivalent display on self-assembled peptide and protein materials. In addition, recent examples of supramolecular peptide materials that rely on the multivalent display of chemical signals for the desired applications are presented. Collectively, this discussion illustrates the potential of self-assembled peptides as sustainable materials to address challenges in contemporary materials science and provides principles for the design of next-generation agents for a variety of applications.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
