Bioorthogonal chemistries for nanomaterial conjugation and targeting

Rahim, Maha K.; Kota, Rajesh; Lee, Sumi; Haun, Jered B.

doi:10.1515/nano.0034.00041

Cited by 7 publications

(14 citation statements)

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“…1-5 These works utilize the concept of pretargeting, where a chemically-tagged affinity molecule such as a monoclonal antibody is first applied to mark the target site, followed by covalent attachment of the contrast agent. 6,7 Due to poor in vivo pharmacokinetics or other limitations of a traditional direct conjugate, pretargeting has been shown to improve imaging capabilities under different modalities in animal models.…”

Section: Introductionmentioning

confidence: 99%

Enhancing Reactivity for Bioorthogonal Pretargeting by Unmasking Antibody-Conjugated trans-Cyclooctenes

2015

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The bioorthogonal cycloaddition reaction between tetrazine and trans-cyclooctene (TCO) is rapidly growing in use for molecular imaging and cell-based diagnostics. We have surprisingly uncovered that the majority of TCOs conjugated to monoclonal antibodies using standard amine-coupling procedures are non-reactive. We show that antibody-bound TCOs are not inactivated by trans-cis isomerization and that the bulky cycloaddition reaction is not sterically hindered. Instead, TCOs are likely masked by hydrophobic interactions with the antibody. We show that introducing TCO via hydrophilic polyethyleneglycol (PEG) linkers can fully preserve reactivity, resulting in >5-fold enhancement in functional density without affecting antibody binding. This is accomplished using a novel dual bioorthogonal approach in which heterobifunctional dibenzylcyclooctyne (DBCO)-PEG-TCO molecules are reacted with azido-antibodies. Improved imaging capabilities are demonstrated for different cancer biomarkers using tetrazine-modified fluorophore and quantum dot probes. We believe that the PEG linkers prevent TCOs from burying within the antibody during conjugation, which could be relevant to other bioorthogonal tags and biomolecules. We expect the improved TCO reactivity obtained using the reported methods will significantly advance bioorthogonal pretargeting applications.

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Section: Introductionmentioning

confidence: 99%

Enhancing Reactivity for Bioorthogonal Pretargeting by Unmasking Antibody-Conjugated trans-Cyclooctenes

2015

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“…47 In this approach, a reactive bioorthogonal motif ( trans -cyclooctene, TCO; inverse electron-demand Diels–Alder reaction, k 2 ≈ 10 4 M −1 ·s −1 ) 39,46 is encapsulated into an SNP vector to provide TCO⊂SNPs with a uniform size of ca. 100 nm (Figure 1a).…”

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confidence: 99%

Pretargeted Positron Emission Tomography Imaging That Employs Supramolecular Nanoparticles with in Vivo Bioorthogonal Chemistry

et al. 2016

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A pretargeted oncologic positron emission tomography (PET) imaging that leverages the power of supramolecular nanoparticles with in vivo bioorthogonal chemistry was demonstrated for the clinically relevant problem of tumor imaging. The advantages of this approach are that (i) the pharmacokinetics (PKs) of tumor-targeting and imaging agents can be independently altered via chemical alteration to achieve the desired in vivo performance and (ii) the interplay between the two PKs and other controllable variables confers a second layer of control toward improved PET imaging. In brief, we utilized supramolecular chemistry to synthesize tumor-targeting nanoparticles containing transcyclooctene (TCO, a bioorthogonal reactive motif), called TCO⊂SNPs. After the intravenous injection and subsequent concentration of the TCO⊂SNPs in the tumors of living mice, a small molecule containing both the complementary bioorthogonal motif (tetrazine, Tz) and a positron-emitting radioisotope (64Cu) was injected to react selectively and irreversibly to TCO. High-contrast PET imaging of the tumor mass was accomplished after the rapid clearance of the unreacted 64Cu-Tz probe. Our nanoparticle approach encompasses a wider gamut of tumor types due to the use of EPR effects, which is a universal phenomenon for most solid tumors.

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“…Our meta-analysis reveals that the most documented click reaction for NPs in the literature is copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), representing more than the half of the listed publications (Figurea). stable 1,2,3 triazole 17 with a fast reaction speed (second-order rate constant k 2 up to 10 4 M -1 s -1 ) 52 and reproducible results in physiological conditions (Figure). 18 Modification of the NP surface for specific cell interactions generally involves a first step allowing chemical binding of an alkyne or azide on the surface, followed by a second step to add the biomolecules.…”

Section: Copper(i)-catalyzed Azide-alkyne [3+2] Cycloaddition (Cuaac)mentioning

confidence: 62%

Click and Bioorthogonal Chemistry: The Future of Active Targeting of Nanoparticles for Nanomedicines?

et al. 2021

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Over the years, click and bioorthogonal reactions have been the subject of considerable research efforts. These high-performance chemical reactions have been developed to meet requirements not often provided by the chemical reactions commonly used today in the biological environment, such as selectivity, rapid reaction rate and biocompatibility. Click and bioorthogonal reactions have been attracting increasing attention in the biomedical field for the engineering of nanomedicines. In this review, we study a compilation of articles from 2014 to the present, using the terms "click chemistry and nanoparticles (NPs)" to highlight the application of this type of chemistry for applications involving NPs intended for biomedical applications. This study identifies the main strategies offered by click and bioorthogonal chemistry, with respect to passive and active targeting, for NP functionalization with specific and multiple properties for imaging and cancer therapy. In the final part, a novel and promising approach for "two step" targeting of NPs, called pretargeting (PT), is also discussed; the principle of this strategy as well as all the studies listed from 2014 to the present are presented in more detail.

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Bioorthogonal chemistries for nanomaterial conjugation and targeting

Cited by 7 publications

References 0 publications

Enhancing Reactivity for Bioorthogonal Pretargeting by Unmasking Antibody-Conjugated trans-Cyclooctenes

Enhancing Reactivity for Bioorthogonal Pretargeting by Unmasking Antibody-Conjugated trans-Cyclooctenes

Pretargeted Positron Emission Tomography Imaging That Employs Supramolecular Nanoparticles with in Vivo Bioorthogonal Chemistry

Click and Bioorthogonal Chemistry: The Future of Active Targeting of Nanoparticles for Nanomedicines?

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