Targeted and modular architectural polymers employing bioorthogonal chemistry for quantitative therapeutic delivery

Ediriweera, Gayathri R.; Simpson, Joshua D.; Fuchs, Adrian V.; Venkatachalam, T. K.; Walle, Matthias Van De; Howard, Christopher B.; Mahler, Stephen M.; Blinco, James P.; Fletcher, Nicholas L.; Houston, Zachary H.; Bell, Craig A.; Thurecht, Kristofer J.

doi:10.1039/d0sc00078g

Cited by 25 publications

(27 citation statements)

References 55 publications

(80 reference statements)

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“…The clicked molecule can then be monitored via PET imaging to monitor drug delivery in real-time, thereby generating an advanced theranostic system (Figure 4). [50] We anticipate these specific bioorthogonal "click" approaches and future iterations based on pre-targeted nanomedicines to be promising candidates for highly specific drug delivery and imaging approaches for otherwise poorly responding malignancies.…”

Section: Mechanisms To Deploy a Bolus Of Drug At The Tumor Sitementioning

confidence: 99%

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Next‐Generation Polymeric Nanomedicines for Oncology: Perspectives and Future Directions

Fletcher

Kempe

Thurecht

2020

Macromol. Rapid Commun.

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Precision polymers as advanced nanomedicines represent an appealing approach for the treatment of otherwise untreatable malignancies. By taking advantage of unique nanomaterial properties and implementing judicious design strategies, polymeric nanomedicines are able to be produced that overcome many barriers to effective treatment. Current key research focus areas anticipated to produce the greatest impact in polymer applications in nanomedicine for oncology include new strategies to achieve “active” targeting, polymeric pro‐drug activation, and combinatorial polymer drug delivery approaches in combination with enhanced understanding of complex bio‐nano interactions. These approaches, both in isolation or combination, form the next generation of precision nanomedicines with significant anticipated future health outcomes. Of necessity, these approaches will combine an intimate understanding of biological interactions with advanced materials design. This perspectives piece aims to highlight emerging opportunities that promise to be game changers in the nanomedicine oncology field. Discussed herein are current and next generation polymeric nanomedicines with a focus towards structures that are, or could, undergo clinical translation as well as highlight key advances in the field.

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Section: Mechanisms To Deploy a Bolus Of Drug At The Tumor Sitementioning

confidence: 99%

“…The clicked molecule can then be monitored via PET imaging to monitor drug delivery in real‐time, thereby generating an advanced theranostic system ( Figure ). [ 50 ]…”

Section: Mechanisms To Deploy a Bolus Of Drug At The Tumor Sitementioning

confidence: 99%

Next‐Generation Polymeric Nanomedicines for Oncology: Perspectives and Future Directions

Fletcher

Kempe

Thurecht

2020

Macromol. Rapid Commun.

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“…[19] Early pioneering work in the field of bioorthogonal chemistry realized the critical importance of the pharmacokinetics of reactive species as a limiting factor to in vivo translation; polymer functionalized reagents offered a way to optimize these pharmacokinetic parameters, allowing for efficient in vivo bioorthogonal chemistry. [20,21] Beyond just the pharmacokinetics, polymers can be designed with chemistries or architectures to control the biodistribution, extracellular or intracellular localization, biocompatibility, and excretion profile of the bioorthogonal reagents. [21] This allows the optimization of photochemical groups for their reactivity and selectivity, with less consideration for how this affects their physical and biological properties.…”

Section: Design Parameters For Bioorthogonal Polymer Photochemistrymentioning

confidence: 99%

“…[20,21] Beyond just the pharmacokinetics, polymers can be designed with chemistries or architectures to control the biodistribution, extracellular or intracellular localization, biocompatibility, and excretion profile of the bioorthogonal reagents. [21] This allows the optimization of photochemical groups for their reactivity and selectivity, with less consideration for how this affects their physical and biological properties. The molecular size, solubility, toxicity, and cell permeability ( Figure 1) are some of the parameters now governed by the nature of the polymer carrier, and examples of this benefit from the literature will be highlighted throughout Section 4.…”

Section: Design Parameters For Bioorthogonal Polymer Photochemistrymentioning

confidence: 99%

Shining a Light on Bioorthogonal Photochemistry for Polymer Science

Boase

2020

Macromol. Rapid Commun.

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Bioorthogonal chemistry is revolutionizing the fields of biological chemistry and nanomedicine, providing tools to actively probe and perturb native biochemical processes. Photochemistry provides the opportunity to actively and non‐invasively control bioorthogonal reactions, providing sophisticated optochemical tools. Despite the opportunities in bioorthogonal photochemistry, there remain many significant challenges to the clinical translation of current research. This review aims to provide an overview of these challenges and highlight recent examples from the literature that are providing revolutionary solutions to overcoming these barriers. It will highlight new photochemical systems that can be triggered by near infrared light in aqueous solutions and have been demonstrated to function in complex biological systems, including in living animals. It will cover diverse classes of photochemical reactions including photopolymerization, uncaging, conjugation, and photoswitching. The discussion will detail how new approaches are being integrated into polymers or highlight unexploited opportunities. This review intends to showcase how the unique synergy of bioorthogonal photochemistry and polymer science provides vast opportunities in the fields of biomaterials, nanomedicine, and theranostics. This will hopefully provide inspiration to material scientists to integrate bioorthogonal photochemistry into new adaptable materials and ensure translation to solve clinical challenges.

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“…The toolbox of TCO moieties that can be directly attached to an antibody without interfering its bio-function is to be expanded. Thurecht's group developed a novel polymer-drug conjugate for a three-component system ( Figure 15C) [115]: (1) a TCO-Dox prodrug conjugated to a PEGylated hyperbranched polymer (HBP); (2) a PEGylated tetrazine trigger functionalized with the 64 Cu chelator NOTA; (3) a bispecific antibody (BsAb) that recognized tumor-associated glycoprotein-72 as well as PEGylated nanoparticles via strong non-covalent interactions. Firstly, the HBP-TCO-Dox was incubated with BsAb (at a ratio of 1:1) for one hour and then the conjugate was injected intravenously to MCF7-tumor-bearing mice.…”

Section: Antibody-drug Conjugates (Adcs)mentioning

confidence: 99%

Activation and Delivery of Tetrazine-Responsive Bioorthogonal Prodrugs

Wang

Zhang

et al. 2020

Molecules

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Prodrugs, which remain inert until they are activated under appropriate conditions at the target site, have emerged as an attractive alternative to drugs that lack selectivity and show off-target effects. Prodrugs have traditionally been activated by enzymes, pH or other trigger factors associated with the disease. In recent years, bioorthogonal chemistry has allowed the creation of prodrugs that can be chemically activated with spatio-temporal precision. In particular, tetrazine-responsive bioorthogonal reactions can rapidly activate prodrugs with excellent biocompatibility. This review summarized the recent development of tetrazine bioorthogonal cleavage reaction and great promise for prodrug systems.

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Targeted and modular architectural polymers employing bioorthogonal chemistry for quantitative therapeutic delivery

Abstract: There remain several key challenges to existing therapeutic systems for cancer therapy, such as quantitatively determining the true, tissue-specific drug release profile in vivo, as well as reducing side-effects for an increased standard of care.

Cited by 25 publications

References 55 publications

Next‐Generation Polymeric Nanomedicines for Oncology: Perspectives and Future Directions

Next‐Generation Polymeric Nanomedicines for Oncology: Perspectives and Future Directions

Shining a Light on Bioorthogonal Photochemistry for Polymer Science

Activation and Delivery of Tetrazine-Responsive Bioorthogonal Prodrugs

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