Development of multifunctional poly(glycidyl methacrylate) (PGMA) nanoparticles for targeted cancer therapy and imaging

Ruhani Singh

Research output: ThesisDoctoral Thesis

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Abstract

[Truncated] Nanoparticle based chemotherapy has been predicated to be one of the frontrunners in the field of cancer diagnosis and treatment. Currently, nanoparticle-mediated cancer targeted therapy mainly relies on the abnormal tumor microenvironment for distribution and retention of the nanoparticles. The design and development of multifunctional second-generation nanoparticles seek to expand upon the benefits of these firstgeneration nanoparticles by combining therapeutic and diagnostic functions within a single formulation and are commonly referred to as “theranostic” agents. These agents can simultaneously deliver imaging probes and therapeutics to specific sites or organs, enabling detection and treatment of disease in a single procedure. Theranostic agents are expected to inform us about localization of the drug and pathological processes longitudinally. This will help make informed decisions about timing, dosage, drug choice, and treatment strategies. However, any additional design feature in drug development will come at the cost of additional regulatory, production, and financial hurdles. The trade-off between these “costs” and clinical benefit will be highly dependent on the choices made when designing drug nanoparticles. Considering these aforementioned criteria, for successful clinical translation, preclinical development of a multifunctional nanoformulation needs to encompass utilization of simple and efficient conjugation methodologies, pertinent yet readily available and cost-effective targeting ligands, and assessment of efficacy in relevant animal models that mimic the clinical situation.

The work presented in this thesis is a systematic progression from development to validation of poly(glycidyl methacrylate) (PGMA) based multifunctional nanoparticles as versatile nanocarriers for receptor-mediated targeted delivery, in models of ovarian and prostate cancers, in vitro and in vivo respectively. The availability of the epoxide functionality in PGMA enables efficient functionalization through nucleophilic ring opening reactions making PGMA an ideal platform for the conjugation of targeting ligands.

Original languageEnglish
QualificationDoctor of Philosophy
Publication statusUnpublished - 2015

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