The overall emphasis of this dissertation research included two kinds of asymmetrically-functionalized nanoparticles with anisotropic distributions of chemical functionalities, three degradable polymers synthesized by organocatalyzed ring-opening polymerizations, and two polyphosphoester-based nanoparticle systems for various biomedical applications.
Inspired by the many hierarchical assembly processes that afford complex materials in Nature, the construction of asymmetrically-functionalized nanoparticles with efficient surface chemistries and the directional organization of those building blocks into complex structures have attracted much attention. The first method generated a Janus-faced polymer nanoparticle that presented two orthogonally click-reactive surface chemistries, thiol and azido. This robust method involved reactive functional group transfer by templating against gold nanoparticle substrates. The second method produced nanoparticles with sandwich-like distribution of crown ether functionalities through a stepwise self-assembly process that utilized crown ether-ammonium supramolecular interactions to mediate inter-particle association and the local intra-particle phase separation of unlike hydrophobic polymers.
With the goal to improve the efficiency of the production of degradable polymers with tunable chemical and physical properties, a new type of reactive polyphosphoester was synthesized bearing alkynyl groups by an organocatalyzed ring-opening polymerization, the chemical availability of the alkyne groups was investigated by employing \"click\" type azide-alkyne Huisgen cycloaddition and thiol-yne radical-mediated reactions. Based on this alkyne-functionalized polyphosphoester polymer and its two available \"click\" type reactions, two degradable nanoparticle systems were developed. To develop the first system, the well defined poly(ethylene oxide)-block-polyphosphester diblock copolymer was transformed into a multifunctional Paclitaxel drug conjugate by densely attaching the polyphosphoester block with azide-functionalized Paclitaxel by azide-alkyne Huisgen cycloaddition. This Paclitaxel drug conjugate provides a powerful platform for combinational cancer therapy and bioimaging due to its ultra-high Paclitaxel loading: > 65 wt%), high water solubility: >6.2 mg/mL for PTX) and easy functionalization. Another polyphosphoester-based nanoparticle system has been developed by a programmable process for the rapid and facile preparation of a family of nanoparticles with different surface charges and functionalities. The non-ionic, anionic, cationic and zwitterionic nanoparticles with hydrodynamic diameters between 13 nm to 21 nm and great size uniformity could be rapidly prepared from small molecules in 6 h or 2 days. The anionic and zwitterionic nanoparticles were designed to load silver ions to treat pulmonary infections, while the cationic nanoparticles are being applied to regulate lung injuries by serving as a degradable iNOS inhibitor conjugates.
In addition, a direct synthesis of acid-labile polyphosphoramidate by organobase-catalyzed ring-opening polymerization and an improved two-step preparation of polyphosphoester ionomer by acid-assisted cleavage of phosphoramidate bonds on polyphosphoramidate were developed. Polyphosphoramidate and polyphosphoester ionomers may be applied to many applications, due to their unique chemical and physical properties.
","abstract_html":"<p>The overall emphasis of this dissertation research included two kinds of asymmetrically-functionalized nanoparticles with anisotropic distributions of chemical functionalities, three degradable polymers synthesized by organocatalyzed ring-opening polymerizations, and two polyphosphoester-based nanoparticle systems for various biomedical applications.</p><p>Inspired by the many hierarchical assembly processes that afford complex materials in Nature, the construction of asymmetrically-functionalized nanoparticles with efficient surface chemistries and the directional organization of those building blocks into complex structures have attracted much attention. The first method generated a Janus-faced polymer nanoparticle that presented two orthogonally click-reactive surface chemistries, thiol and azido. This robust method involved reactive functional group transfer by templating against gold nanoparticle substrates. The second method produced nanoparticles with sandwich-like distribution of crown ether functionalities through a stepwise self-assembly process that utilized crown ether-ammonium supramolecular interactions to mediate inter-particle association and the local intra-particle phase separation of unlike hydrophobic polymers.</p><p>With the goal to improve the efficiency of the production of degradable polymers with tunable chemical and physical properties, a new type of reactive polyphosphoester was synthesized bearing alkynyl groups by an organocatalyzed ring-opening polymerization, the chemical availability of the alkyne groups was investigated by employing "click" type azide-alkyne Huisgen cycloaddition and thiol-yne radical-mediated reactions. Based on this alkyne-functionalized polyphosphoester polymer and its two available "click" type reactions, two degradable nanoparticle systems were developed. To develop the first system, the well defined poly(ethylene oxide)-block-polyphosphester diblock copolymer was transformed into a multifunctional Paclitaxel drug conjugate by densely attaching the polyphosphoester block with azide-functionalized Paclitaxel by azide-alkyne Huisgen cycloaddition. This Paclitaxel drug conjugate provides a powerful platform for combinational cancer therapy and bioimaging due to its ultra-high Paclitaxel loading: > 65 wt%), high water solubility: >6.2 mg/mL for PTX) and easy functionalization. Another polyphosphoester-based nanoparticle system has been developed by a programmable process for the rapid and facile preparation of a family of nanoparticles with different surface charges and functionalities. The non-ionic, anionic, cationic and zwitterionic nanoparticles with hydrodynamic diameters between 13 nm to 21 nm and great size uniformity could be rapidly prepared from small molecules in 6 h or 2 days. The anionic and zwitterionic nanoparticles were designed to load silver ions to treat pulmonary infections, while the cationic nanoparticles are being applied to regulate lung injuries by serving as a degradable iNOS inhibitor conjugates.</p><p>In addition, a direct synthesis of acid-labile polyphosphoramidate by organobase-catalyzed ring-opening polymerization and an improved two-step preparation of polyphosphoester ionomer by acid-assisted cleavage of phosphoramidate bonds on polyphosphoramidate were developed. Polyphosphoramidate and polyphosphoester ionomers may be applied to many applications, due to their unique chemical and physical properties.</p>","abstract_has_math":false,"creators":["Zhang, Shiyi"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":["Karen L. Wooley"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013-03-25T07:00:00Z","date_published":"2013-03-25T07:00:00Z","updated_at":"2026-07-24T06:12:25Z","subjects":["Chemistry"],"languages":["English (en)"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier.doi","label":"DOI","values":["https://doi.org/10.7936/K7WW7FQQ"],"render_values":[{"text":"https://doi.org/10.7936/K7WW7FQQ","href":"https://doi.org/10.7936/K7WW7FQQ","code":true}]}]},"links":{"outbound_url":"https://openscholarship.wustl.edu/etd/1075","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Karen L. Wooley"]},{"key":"dc:creator","label":"Author","values":["Zhang, Shiyi"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2013-08-26T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Chemistry"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["English (en)"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://openscholarship.wustl.edu/etd/1075"]},{"key":"dc:identifier.doi","label":"DOI","values":["https://doi.org/10.7936/K7WW7FQQ"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The overall emphasis of this dissertation research included two kinds of asymmetrically-functionalized nanoparticles with anisotropic distributions of chemical functionalities, three degradable polymers synthesized by organocatalyzed ring-opening polymerizations, and two polyphosphoester-based nanoparticle systems for various biomedical applications.
Inspired by the many hierarchical assembly processes that afford complex materials in Nature, the construction of asymmetrically-functionalized nanoparticles with efficient surface chemistries and the directional organization of those building blocks into complex structures have attracted much attention. The first method generated a Janus-faced polymer nanoparticle that presented two orthogonally click-reactive surface chemistries, thiol and azido. This robust method involved reactive functional group transfer by templating against gold nanoparticle substrates. The second method produced nanoparticles with sandwich-like distribution of crown ether functionalities through a stepwise self-assembly process that utilized crown ether-ammonium supramolecular interactions to mediate inter-particle association and the local intra-particle phase separation of unlike hydrophobic polymers.
With the goal to improve the efficiency of the production of degradable polymers with tunable chemical and physical properties, a new type of reactive polyphosphoester was synthesized bearing alkynyl groups by an organocatalyzed ring-opening polymerization, the chemical availability of the alkyne groups was investigated by employing \"click\" type azide-alkyne Huisgen cycloaddition and thiol-yne radical-mediated reactions. Based on this alkyne-functionalized polyphosphoester polymer and its two available \"click\" type reactions, two degradable nanoparticle systems were developed. To develop the first system, the well defined poly(ethylene oxide)-block-polyphosphester diblock copolymer was transformed into a multifunctional Paclitaxel drug conjugate by densely attaching the polyphosphoester block with azide-functionalized Paclitaxel by azide-alkyne Huisgen cycloaddition. This Paclitaxel drug conjugate provides a powerful platform for combinational cancer therapy and bioimaging due to its ultra-high Paclitaxel loading: > 65 wt%), high water solubility: >6.2 mg/mL for PTX) and easy functionalization. Another polyphosphoester-based nanoparticle system has been developed by a programmable process for the rapid and facile preparation of a family of nanoparticles with different surface charges and functionalities. The non-ionic, anionic, cationic and zwitterionic nanoparticles with hydrodynamic diameters between 13 nm to 21 nm and great size uniformity could be rapidly prepared from small molecules in 6 h or 2 days. The anionic and zwitterionic nanoparticles were designed to load silver ions to treat pulmonary infections, while the cationic nanoparticles are being applied to regulate lung injuries by serving as a degradable iNOS inhibitor conjugates.
In addition, a direct synthesis of acid-labile polyphosphoramidate by organobase-catalyzed ring-opening polymerization and an improved two-step preparation of polyphosphoester ionomer by acid-assisted cleavage of phosphoramidate bonds on polyphosphoramidate were developed. Polyphosphoramidate and polyphosphoester ionomers may be applied to many applications, due to their unique chemical and physical properties.
"]},{"key":"dc:title","label":"Title","values":["Rapid, Efficient and Versatile Strategies for Functionally Sophisticated Polymers and Nanoparticles: Degradable Polyphosphoesters and Anisotropic Distribution of Chemical Functionalities"]}]}],"canonical_facts":{"dc:contributor":["Karen L. Wooley"],"dc:creator":["Zhang, Shiyi"],"dc:date.available":["2013-08-26T07:00:00Z"],"dc:description.abstract":["The overall emphasis of this dissertation research included two kinds of asymmetrically-functionalized nanoparticles with anisotropic distributions of chemical functionalities, three degradable polymers synthesized by organocatalyzed ring-opening polymerizations, and two polyphosphoester-based nanoparticle systems for various biomedical applications.
Inspired by the many hierarchical assembly processes that afford complex materials in Nature, the construction of asymmetrically-functionalized nanoparticles with efficient surface chemistries and the directional organization of those building blocks into complex structures have attracted much attention. The first method generated a Janus-faced polymer nanoparticle that presented two orthogonally click-reactive surface chemistries, thiol and azido. This robust method involved reactive functional group transfer by templating against gold nanoparticle substrates. The second method produced nanoparticles with sandwich-like distribution of crown ether functionalities through a stepwise self-assembly process that utilized crown ether-ammonium supramolecular interactions to mediate inter-particle association and the local intra-particle phase separation of unlike hydrophobic polymers.
With the goal to improve the efficiency of the production of degradable polymers with tunable chemical and physical properties, a new type of reactive polyphosphoester was synthesized bearing alkynyl groups by an organocatalyzed ring-opening polymerization, the chemical availability of the alkyne groups was investigated by employing \"click\" type azide-alkyne Huisgen cycloaddition and thiol-yne radical-mediated reactions. Based on this alkyne-functionalized polyphosphoester polymer and its two available \"click\" type reactions, two degradable nanoparticle systems were developed. To develop the first system, the well defined poly(ethylene oxide)-block-polyphosphester diblock copolymer was transformed into a multifunctional Paclitaxel drug conjugate by densely attaching the polyphosphoester block with azide-functionalized Paclitaxel by azide-alkyne Huisgen cycloaddition. This Paclitaxel drug conjugate provides a powerful platform for combinational cancer therapy and bioimaging due to its ultra-high Paclitaxel loading: > 65 wt%), high water solubility: >6.2 mg/mL for PTX) and easy functionalization. Another polyphosphoester-based nanoparticle system has been developed by a programmable process for the rapid and facile preparation of a family of nanoparticles with different surface charges and functionalities. The non-ionic, anionic, cationic and zwitterionic nanoparticles with hydrodynamic diameters between 13 nm to 21 nm and great size uniformity could be rapidly prepared from small molecules in 6 h or 2 days. The anionic and zwitterionic nanoparticles were designed to load silver ions to treat pulmonary infections, while the cationic nanoparticles are being applied to regulate lung injuries by serving as a degradable iNOS inhibitor conjugates.
In addition, a direct synthesis of acid-labile polyphosphoramidate by organobase-catalyzed ring-opening polymerization and an improved two-step preparation of polyphosphoester ionomer by acid-assisted cleavage of phosphoramidate bonds on polyphosphoramidate were developed. Polyphosphoramidate and polyphosphoester ionomers may be applied to many applications, due to their unique chemical and physical properties.
"],"dc:identifier":["https://openscholarship.wustl.edu/etd/1075"],"dc:identifier.doi":["https://doi.org/10.7936/K7WW7FQQ"],"dc:language":["English (en)"],"dc:subject":["Chemistry"],"dc:title":["Rapid, Efficient and Versatile Strategies for Functionally Sophisticated Polymers and Nanoparticles: Degradable Polyphosphoesters and Anisotropic Distribution of Chemical Functionalities"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T06:12:25Z"}