Development of novel polymeric nanoparticles with tailored architectures and functionalities/

Developing a modular synthetic route to a combinatorial library of functional nanoparticles for applications like drug delivery is one of the main interests of our group. To this end, we have envisioned a novel nanoparticle architecture called a brush-arm star polymer (BASP), which has polymer brushes on the periphery shielding the core. Such nanoparticles were synthesized by, first, "graft-through" ring-opening metathesis polymerization (ROMP) of a norbornene-macromonomer to create the brush-arms, and second, cross-linking the arms with a bis-norbornene cross-linker to afford star polymers via the "arm-first" star polymer method. Functionality can be installed into the macromonomer (MM) or crosslinker preand post-polymerization. We took advantage of the highly efficient third-generation Grubbs catalyst to polymerize a polyethylene glycol (PEG) macromonomer (MM) and a bisnorbornene nitrobenzyloxycarbonyl (NBOC) photocleavable cross-linker to cross-link the brush-arms, which led to low-dispersity (Đ </=1.23) core-degradable BASPs. Controlled degradation of these star polymers was achieved by UV irradiation (365 nm). Next, a novel branched norbornene-polystyrene (PS)-polylactide (PLA)-MM was used to create pseudo-alternating copolymers and miktoarm-BASPs. Transmission electron miscroscopy (TEM) of these star polymers revealed nanoparticles with segregated domains. Also, new cross-linkers were explored containing two different bis-norbornene reversible addition-fragmentation chain-transfer (RAFT) agents. A more flexible RAFT initiator crosslinker led to high-dispersity (Đ >\=1.52) BASPs, while the more rigid RAFT initiator crosslinker led to low-dispersity (Đ </=1.05) BASPs. Finally, doxorubicin-loaded, photocleavable drug vector BASPs were synthesized from azide-functionalized BASPs. Copper-catalyzed azide-alkyne cycloaddition (CuAAC) was utilized to covalently link doxorubicin to the azide BASPs, post-polymerization. These BASPs degraded and simultaneously released their drug payload upon UV irradiation. MTT assays were conducted with these nanoparticles on MCF-7 human breast cancer cells and were shown to be non-toxic before UV irradiation and toxic afterward.

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Chemistry.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2013

Author dc:creator

• Burts, Alan O. (Alan Omar)

Advisor dc:contributor.advisor

• Jeremiah A. Johnson.

• Chemistry.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/82334

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/82334