Alternative Chemistries for Free Radical-Initiated Targeting and Immobilization
Stimuli-responsive biomaterials are an emerging strategy that leverage common pathophysiological triggers to target drug delivery to limit or avoid toxic side effects. Native free radicals, such as reactive oxygen species (ROS), are widely upregulated in many pathological states. We have previously...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Journal of Functional Biomaterials |
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| Online Access: | https://www.mdpi.com/2079-4983/14/3/153 |
| _version_ | 1797610924694044672 |
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| author | Emily T. DiMartini Christopher J. Lowe David I. Shreiber |
| author_facet | Emily T. DiMartini Christopher J. Lowe David I. Shreiber |
| author_sort | Emily T. DiMartini |
| collection | DOAJ |
| description | Stimuli-responsive biomaterials are an emerging strategy that leverage common pathophysiological triggers to target drug delivery to limit or avoid toxic side effects. Native free radicals, such as reactive oxygen species (ROS), are widely upregulated in many pathological states. We have previously demonstrated that native ROS are capable of crosslinking and immobilizing acrylated polyethylene glycol diacrylate (PEGDA) networks and coupled payloads in tissue mimics, providing evidence for a potential targeting mechanism. To build on these promising results, we evaluated PEG dialkenes and dithiols as alternative polymer chemistries for targeting. The reactivity, toxicity, crosslinking kinetics, and immobilization potential of PEG dialkenes and dithiols were characterized. Both the alkene and thiol chemistries crosslinked in the presence of ROS, generating high molecular weight polymer networks that immobilized fluorescent payloads in tissue mimics. Thiols were especially reactive and even reacted with acrylates in the absence of free radicals, and this motivated us to explore a two-phase targeting approach. Delivering thiolated payloads in a second phase, after the initial polymer net formation, allowed greater control over the payload dosing and timing. Two-phase delivery combined with a library of radical-sensitive chemistries can enhance the versatility and flexibility of this free radical-initiated platform delivery system. |
| first_indexed | 2024-03-11T06:20:46Z |
| format | Article |
| id | doaj.art-13bcc93b963140b7b54271c789542eee |
| institution | Directory Open Access Journal |
| issn | 2079-4983 |
| language | English |
| last_indexed | 2024-03-11T06:20:46Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Functional Biomaterials |
| spelling | doaj.art-13bcc93b963140b7b54271c789542eee2023-11-17T11:54:20ZengMDPI AGJournal of Functional Biomaterials2079-49832023-03-0114315310.3390/jfb14030153Alternative Chemistries for Free Radical-Initiated Targeting and ImmobilizationEmily T. DiMartini0Christopher J. Lowe1David I. Shreiber2Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USADepartment of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USADepartment of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USAStimuli-responsive biomaterials are an emerging strategy that leverage common pathophysiological triggers to target drug delivery to limit or avoid toxic side effects. Native free radicals, such as reactive oxygen species (ROS), are widely upregulated in many pathological states. We have previously demonstrated that native ROS are capable of crosslinking and immobilizing acrylated polyethylene glycol diacrylate (PEGDA) networks and coupled payloads in tissue mimics, providing evidence for a potential targeting mechanism. To build on these promising results, we evaluated PEG dialkenes and dithiols as alternative polymer chemistries for targeting. The reactivity, toxicity, crosslinking kinetics, and immobilization potential of PEG dialkenes and dithiols were characterized. Both the alkene and thiol chemistries crosslinked in the presence of ROS, generating high molecular weight polymer networks that immobilized fluorescent payloads in tissue mimics. Thiols were especially reactive and even reacted with acrylates in the absence of free radicals, and this motivated us to explore a two-phase targeting approach. Delivering thiolated payloads in a second phase, after the initial polymer net formation, allowed greater control over the payload dosing and timing. Two-phase delivery combined with a library of radical-sensitive chemistries can enhance the versatility and flexibility of this free radical-initiated platform delivery system.https://www.mdpi.com/2079-4983/14/3/153free radicalsstimuli-responsive drug deliverybiopolymersreactive oxygen speciesside effects |
| spellingShingle | Emily T. DiMartini Christopher J. Lowe David I. Shreiber Alternative Chemistries for Free Radical-Initiated Targeting and Immobilization Journal of Functional Biomaterials free radicals stimuli-responsive drug delivery biopolymers reactive oxygen species side effects |
| title | Alternative Chemistries for Free Radical-Initiated Targeting and Immobilization |
| title_full | Alternative Chemistries for Free Radical-Initiated Targeting and Immobilization |
| title_fullStr | Alternative Chemistries for Free Radical-Initiated Targeting and Immobilization |
| title_full_unstemmed | Alternative Chemistries for Free Radical-Initiated Targeting and Immobilization |
| title_short | Alternative Chemistries for Free Radical-Initiated Targeting and Immobilization |
| title_sort | alternative chemistries for free radical initiated targeting and immobilization |
| topic | free radicals stimuli-responsive drug delivery biopolymers reactive oxygen species side effects |
| url | https://www.mdpi.com/2079-4983/14/3/153 |
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