Orientation‐Controlled Conjugation of Haloalkane Dehalogenase Fused Homing Peptides to Multifunctional Nanoparticles for the Specific Recognition of Cancer Cells

Mazzucchelli, Serena; Colombo, Miriam; Verderio, Paolo; Rozek, Ewa; Andreata, Francesco; Galbiati, Elisabetta; Tortora, Paolo; Corsi, Fabio; Prosperi, Davide

doi:10.1002/anie.201209662

Cited by 40 publications

(18 citation statements)

References 30 publications

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“…In a recent research from our group, Halo tag was used as nanoparticle capture module, taking advantage of a new covalent bond formation by site‐specific reaction with a chloro‐alkane linker immobilized on the surface of an IONP. Expressing Halo Tag in fusion with a small peptide of 11 amino acids (U11) with a high affinity for urokinase plasminogen activator receptor (uPAR), we were able to successfully label cancer cells in an orientation‐controlled manner . Similarly, Ting and co‐workers used Halo tag‐conjugated QDs for labeling of specific membrane proteins in living cells.…”

Section: Perspectives: Future Developments In Nanoparticle Deliverymentioning

confidence: 99%

“…The first generation is represented by nanomaterials functionalized through basic surface chemistries to assess biocompatibility, enhance cellular uptake, and reduce toxicity. The second generation is focused on nanomaterials with optimized surface boundaries that improve stability and targeting in biological systems . These studies were characterized by two important tasks: “stealthiness” and active targeting.…”

Section: Introductionmentioning

confidence: 99%

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Delivering Colloidal Nanoparticles to Mammalian Cells: A Nano–Bio Interface Perspective

Verderio

Avvakumova

Alessio

et al. 2014

Adv Healthcare Materials

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Understanding the behavior of multifunctional colloidal nanoparticles capable of biomolecular targeting remains a fascinating challenge in materials science with dramatic implications in view of a possible clinical translation. In several circumstances, assumptions on structure-activity relationships have failed in determining the expected responses of these complex systems in a biological environment. The present Review depicts the most recent advances about colloidal nanoparticles designed for use as tools for cellular nanobiotechnology, in particular, for the preferential transport through different target compartments, including cell membrane, cytoplasm, mitochondria, and nucleus. Besides the conventional entry mechanisms based on crossing the cellular membrane, an insight into modern physical approaches to quantitatively deliver nanomaterials inside cells, such as microinjection and electro-poration, is provided. Recent hypotheses on how the nanoparticle structure and functionalization may affect the interactions at the nano-bio interface, which in turn mediate the nanoparticle internalization routes, are highlighted. In addition, some hurdles when this small interface faces the physiological environment and how this phenomenon can turn into different unexpected responses, are discussed. Finally, possible future developments oriented to synergistically tailor biological and chemical properties of nanoconjugates to improve the control over nanoparticle transport, which could open new scenarios in the field of nanomedicine, are addressed.

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Section: Perspectives: Future Developments In Nanoparticle Deliverymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Delivering Colloidal Nanoparticles to Mammalian Cells: A Nano–Bio Interface Perspective

Verderio

Avvakumova

Alessio

et al. 2014

Adv Healthcare Materials

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“…Haloalkane dehalogenases (HLDs; EC 3.8.1.5) are enzymes that catalyse the hydrolytic cleavage of carbon–halogen bonds in halogenated hydrocarbons to yield the corresponding alcohol, a proton and a halide 17. HLDs have potential applications in bioremediation,18, 19 decontamination,20 industrial biocatalysis,21, 22 biosensing23–25 and cell imaging 26–30. However, their utility in these applications is limited by their low stability and activity under the harsh conditions that are often required 31–33…”

Section: Introductionmentioning

confidence: 99%

Balancing the Stability–Activity Trade‐Off by Fine‐Tuning Dehalogenase Access Tunnels

et al. 2015

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A variant of the haloalkane dehalogenase DhaA with greatly enhanced stability and tolerance of organic solvents but reduced activity was created by mutating four residues in the access tunnel. To create a stabilised enzyme with superior catalytic activity, two of the four originally modified residues were randomised. The resulting mutant F 176 G exhibited 32‐ and 10‐times enhanced activity towards 1,2‐dibromoethane in buffer and 40 % DMSO, respectively, upon retaining high stability. Structural and molecular dynamics analyses demonstrated that the new variant exhibited superior activity because the F 176 G mutation increased the radius of the tunnel’s mouth and the mobility of α‐helices lining the tunnel. The new variant’s tunnel was open in 48 % of trajectories, compared to 58 % for the wild‐type, but only 0.02 % for the original four‐point variant. Delicate balance between activity and stability of enzymes can be manipulated by fine‐tuning the diameter and dynamics of their access tunnels.

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“…To this aim, several strategies have been proposed in the attempt to optimize the surface modification of NPs with organic and biological targeting ligands to improve the NP affinity towards biological receptors4. However, recent developments have pointed out that a few requirements should be taken into account in designing bio-targeted NPs, including tight irreversible (or reversible) binding, and control on density and orientation5678. While several studies have been carried out to achieve a control on linkage stability9, as on ligand orientation and density10, besides some examples1112, a general strategy to introduce a discrete precisely controlled number of targeting biomolecules to each NP is still largely missing.…”

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confidence: 99%

Tumour homing and therapeutic effect of colloidal nanoparticles depend on the number of attached antibodies

et al. 2016

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Active targeting of nanoparticles to tumours can be achieved by conjugation with specific antibodies. Specific active targeting of the HER2 receptor is demonstrated in vitro and in vivo with a subcutaneous MCF-7 breast cancer mouse model with trastuzumab-functionalized gold nanoparticles. The number of attached antibodies per nanoparticle was precisely controlled in a way that each nanoparticle was conjugated with either exactly one or exactly two antibodies. As expected, in vitro we found a moderate increase in targeting efficiency of nanoparticles with two instead of just one antibody attached per nanoparticle. However, the in vivo data demonstrate that best effect is obtained for nanoparticles with only exactly one antibody. There is indication that this is based on a size-related effect. These results highlight the importance of precisely controlling the ligand density on the nanoparticle surface for optimizing active targeting, and that less antibodies can exhibit more effect.

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Orientation‐Controlled Conjugation of Haloalkane Dehalogenase Fused Homing Peptides to Multifunctional Nanoparticles for the Specific Recognition of Cancer Cells

Cited by 40 publications

References 30 publications

Delivering Colloidal Nanoparticles to Mammalian Cells: A Nano–Bio Interface Perspective

Delivering Colloidal Nanoparticles to Mammalian Cells: A Nano–Bio Interface Perspective

Balancing the Stability–Activity Trade‐Off by Fine‐Tuning Dehalogenase Access Tunnels

Tumour homing and therapeutic effect of colloidal nanoparticles depend on the number of attached antibodies

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