Design of Cleavable Monomers and Cross-Linkers for the Synthesis of Degradable Polymer Architectures
Degradable materials, with different chemical compositions and various polymer architectures, are desirable for countless purposes, ranging from biological applications to recyclability of plastic waste. The creation of brand-new materials with useful, desired properties and built-in degradability i...
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| Format: | Thesis |
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Massachusetts Institute of Technology
2024
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| Online Access: | https://hdl.handle.net/1721.1/157815 |
| _version_ | 1824457926704627712 |
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| author | Cardoso da Costa, Leticia |
| author2 | Johnson, Jeremiah A. |
| author_facet | Johnson, Jeremiah A. Cardoso da Costa, Leticia |
| author_sort | Cardoso da Costa, Leticia |
| collection | MIT |
| description | Degradable materials, with different chemical compositions and various polymer architectures, are desirable for countless purposes, ranging from biological applications to recyclability of plastic waste. The creation of brand-new materials with useful, desired properties and built-in degradability is, however, very difficult. The introduction of labile bonds to already known polymers offers, thus, a much simpler approach for the manufacture of degradable materials. Here, we report the design of cleavable monomers and cross-linkers for the synthesis of degradable materials with different polymer architectures. The first half of this thesis focuses on the design of new degradable bottlebrush and brush-arm star polymers (BASPs) via ring-opening metathesis polymerization (ROMP). A brief introduction to the recent advances of bottlebrushes and related nanoarchitectures as a promising carrier platform is provided, followed by the current efforts to impart degradability within the nanoparticle in order to modulate its drug release and clearance rate (Chapter 1). After the introduction, we present the synthesis of boronic ester-crosslinked BASPs that selectively disassemble into bottlebrush fragments upon exposure to hydrogen peroxide, which is often elevated in diseased tissue microenvironments. The H2O2-induced disassembly of spirocyclohexyl nitroxide (chex)-containing BASPs induces a change in transverse magnetic relaxivity that can be detectable via magnetic resonance imaging (MRI) (Chapter 2). In the next chapter, we present the synthesis of backbone-degradable bottlebrush polymers via the co-polymerization of drug-loaded norbornenemacromonomers with a library of tailored silyl ether-based olefins via ring-opening metathesis polymerization (ROMP). The difference in backbone degradation rates, imparted by the silyl ether substituents, leads to different drug release profiles and therapeutic efficacy in vitro (Chapter 3). The second half of this thesis focuses on the introduction of degradable bonds into the polymer backbone of vinylic thermosets via radical ring-opening polymerization (rROP). A brief introduction to the current strategies utilized to impart chemical deconstruction to cross-linked polymer networks prepared by radical polymerization is presented (Chapter 4). Lastly, we improve the performance of a consumer good, gel nail polish, by imparting degradability via co-polymerization with a cleavable comonomer. Gel nail polishes, UV-curable (meth)acrylic coatings, display superior mechanical and adhesive properties compared to alternative nail polishes. These properties, however, come at the expense of ease-of-removal. Here, a cleavable bond is introduced into the resulting cured polymer networks via co-polymerization with a cleavable comonomer. This approach does not impact the material’s properties while enabling easy and fast removal under triggered deconstruction (Chapter 5). |
| first_indexed | 2025-02-19T04:17:46Z |
| format | Thesis |
| id | mit-1721.1/157815 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2025-02-19T04:17:46Z |
| publishDate | 2024 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/1578152024-12-12T04:02:54Z Design of Cleavable Monomers and Cross-Linkers for the Synthesis of Degradable Polymer Architectures Cardoso da Costa, Leticia Johnson, Jeremiah A. Massachusetts Institute of Technology. Department of Chemistry Degradable materials, with different chemical compositions and various polymer architectures, are desirable for countless purposes, ranging from biological applications to recyclability of plastic waste. The creation of brand-new materials with useful, desired properties and built-in degradability is, however, very difficult. The introduction of labile bonds to already known polymers offers, thus, a much simpler approach for the manufacture of degradable materials. Here, we report the design of cleavable monomers and cross-linkers for the synthesis of degradable materials with different polymer architectures. The first half of this thesis focuses on the design of new degradable bottlebrush and brush-arm star polymers (BASPs) via ring-opening metathesis polymerization (ROMP). A brief introduction to the recent advances of bottlebrushes and related nanoarchitectures as a promising carrier platform is provided, followed by the current efforts to impart degradability within the nanoparticle in order to modulate its drug release and clearance rate (Chapter 1). After the introduction, we present the synthesis of boronic ester-crosslinked BASPs that selectively disassemble into bottlebrush fragments upon exposure to hydrogen peroxide, which is often elevated in diseased tissue microenvironments. The H2O2-induced disassembly of spirocyclohexyl nitroxide (chex)-containing BASPs induces a change in transverse magnetic relaxivity that can be detectable via magnetic resonance imaging (MRI) (Chapter 2). In the next chapter, we present the synthesis of backbone-degradable bottlebrush polymers via the co-polymerization of drug-loaded norbornenemacromonomers with a library of tailored silyl ether-based olefins via ring-opening metathesis polymerization (ROMP). The difference in backbone degradation rates, imparted by the silyl ether substituents, leads to different drug release profiles and therapeutic efficacy in vitro (Chapter 3). The second half of this thesis focuses on the introduction of degradable bonds into the polymer backbone of vinylic thermosets via radical ring-opening polymerization (rROP). A brief introduction to the current strategies utilized to impart chemical deconstruction to cross-linked polymer networks prepared by radical polymerization is presented (Chapter 4). Lastly, we improve the performance of a consumer good, gel nail polish, by imparting degradability via co-polymerization with a cleavable comonomer. Gel nail polishes, UV-curable (meth)acrylic coatings, display superior mechanical and adhesive properties compared to alternative nail polishes. These properties, however, come at the expense of ease-of-removal. Here, a cleavable bond is introduced into the resulting cured polymer networks via co-polymerization with a cleavable comonomer. This approach does not impact the material’s properties while enabling easy and fast removal under triggered deconstruction (Chapter 5). Ph.D. 2024-12-11T15:04:07Z 2024-12-11T15:04:07Z 2024-05 2024-12-09T16:27:39.645Z Thesis https://hdl.handle.net/1721.1/157815 In Copyright - Educational Use Permitted Copyright retained by author(s) https://rightsstatements.org/page/InC-EDU/1.0/ application/pdf Massachusetts Institute of Technology |
| spellingShingle | Cardoso da Costa, Leticia Design of Cleavable Monomers and Cross-Linkers for the Synthesis of Degradable Polymer Architectures |
| title | Design of Cleavable Monomers and Cross-Linkers for the Synthesis of Degradable Polymer Architectures |
| title_full | Design of Cleavable Monomers and Cross-Linkers for the Synthesis of Degradable Polymer Architectures |
| title_fullStr | Design of Cleavable Monomers and Cross-Linkers for the Synthesis of Degradable Polymer Architectures |
| title_full_unstemmed | Design of Cleavable Monomers and Cross-Linkers for the Synthesis of Degradable Polymer Architectures |
| title_short | Design of Cleavable Monomers and Cross-Linkers for the Synthesis of Degradable Polymer Architectures |
| title_sort | design of cleavable monomers and cross linkers for the synthesis of degradable polymer architectures |
| url | https://hdl.handle.net/1721.1/157815 |
| work_keys_str_mv | AT cardosodacostaleticia designofcleavablemonomersandcrosslinkersforthesynthesisofdegradablepolymerarchitectures |