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Title: Design and development of polymer-based nanotherapeutics for the treatment of cancer
Author: Schmid, D.
ISNI:       0000 0004 5367 3401
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2016
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The emerging clinical success of nanomaterials over the last two decades is gradually providing oncologists with the technologies to improve the therapeutic outcome of existing and developmental anti-cancer agents. In this thesis, experimental nanoparticle-based cancer therapeutics were developed to induce enhanced cell death combined with the potential to diminish systemic toxicity. Current chemotherapies can induce devastating side-effects in patients. Here it 'was found that the encapsulation of the chemotherapeutic camptothecin in nanoparticles abrogated leucopenic effects and reduced gastrointestinal toxicity; the two main dose-limiting adverse effects of camptothecin-derivativesin the clinic. In addition to a lower toxicity profile, syngeneic tumour growth was inhibited more efficiently when camptothecin was delivered within this optimised drug carrier compared to free drug. , The combination of therapies is a preferred regimen for the treatment of many cancers. ABT- 737 is a promising new anti-cancer drug, but induces thrombocytopenia limiting its therapeutic potential. This effect was alleviated through encapsulation in nanoparticles whilst its cytotoxic activity towards tumour cells was maintained. Excitingly, it was found that ABT- 737 sensitised human colorectal cancer cells to camptothecin-induced apoptosis following combined treatment in a dual-loaded nanoparticle approach. Moreover, a novel antibody-nanoconjugate approach has been explored targeting Death Receptor S which is expressed in high levels in many types of cancer. The presence of DRSspecific antibodies on the nanoparticle clustered receptors on the cell surface of ,..,cancer cells and induced extrinsic apoptosis, more efficiently than free antibody.' These functionalised nanoparticles significantly inhibited growth of colorectal tumours with striking effects when camptothecin is encapsulated in the core and have the potential to overcome resistance. Novel delivery systems may not only widen the therapeutic window of single drugs, but also improve delivery of drug combinations overcoming drug resistance and hopefully facilitating a rapid and successful translation of pre-clinical studies into the clinic.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available