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Synthesis of Stimuli-Responsive Pt-Nanocluster Assembly against Chemoresistant Hepatocellular Carcinoma : 간세포암의 약물저항성에 대응한 자극반응성 Pt 나노클러스터 조립체의 합성
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- Authors
- Advisor
- 현택환
- Major
- 공과대학 화학생물공학부
- Issue Date
- 2017-02
- Publisher
- 서울대학교 대학원
- Keywords
- nanocluster ; functional surface ligand ; self-assembly ; stimuli-responsiveness ; chemoresistance ; drug delivery system ; cancer therapy
- Description
- 학위논문 (석사)-- 서울대학교 대학원 : 화학생물공학부, 2017. 2. 현택환.
- Abstract
- One of the major conundrums of cancer therapy is chemoresistance. A considerable resistance of tumors to conventional chemotherapeutic agents compromises the response rate, and therefore, the overall efficacy of established medical treatments against the disease.
Small-sized platinum (Pt) nanocluster has been spotlighted as an alternative anticancer agent for its potency against cancer cells by virtue of the leached Pt ions. However, nonspecific treatment of Pt nanocluster would also incur toxicity to normal tissues, and this potential risk calls for an intricate delivery system, which would enhance the Pt nanocluster with preferential tumor-targeting and controlled Pt activation and release.
In an effort to further the therapeutic potential of Pt nanocluster with a coordinated delivery system and to overcome the limitations of conventional chemotherapy, we synthesize a Pt-nanocluster assembly (Pt-NA) consisting of polymeric ligands with pH-sensitivity and cancer cell-targeting peptide encapsulating Pt nanoclusters. The Pt-NA is designed in such a way that it would remain latent in circulation, target the sporadic cancer cell subpopulations, release small Pt nanoclusters in acidic subcellular regions via pH-responsive dissociation, and eventually induce damage to diseased cells.
The efficacy of Pt-NA as a prospective anticancer agent is demonstrated in vitro and in vivo in hepatocellular carcinoma (HCC) model, which is often associated with the resistance to Cisplatin, a Pt-based commercial anticancer agent.
- Language
- English
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