Full metadata record
| DC Field | Value | Language |
|---|---|---|
| dc.contributor | Department of Applied Biology and Chemical Technology | en_US |
| dc.contributor.advisor | Law, Ga-lai (ABCT) | en_US |
| dc.contributor.advisor | Wong, Wing-tak (ABCT) | en_US |
| dc.creator | Xu, Weiyuan | - |
| dc.identifier.uri | https://theses.lib.polyu.edu.hk/handle/200/12350 | - |
| dc.language | English | en_US |
| dc.publisher | Hong Kong Polytechnic University | en_US |
| dc.rights | All rights reserved | en_US |
| dc.title | Design and synthesis of functional phthalocyanine conjugates for biological studies | en_US |
| dcterms.abstract | Phthalocyanines (Pcs) have high physical and chemical stabilities, and hydrophilic modification and structural optimization promote their applications in developing diseases therapeutics. As the second-generation photosensitizers (PSs), Pcs have high singlet oxygen quantum yields, low dark toxicity and intense absorption in red region (> 600 nm), which favor them as ideal candidates in photodynamic therapy for cancer treatment. In addition, β-amyloid (Aβ) misfolding and aggregation are one characteristic hallmark in Alzheimer's disease (AD), bringing inhibition of Aβ fibrillization as an optional AD therapy. Pcs can bind with proteins strongly and selectively thus affecting their conformational changes, so it has been widely researched as one potential inhibitor for Aβ aggregation. | en_US |
| dcterms.abstract | Curcumin is a natural product that has been found a series of desirable pharmaceutical properties, including anti-cancer and anti-amyloid. Its interaction with nucleophosmin (NPM1) inside cell nucleus induces cell apoptosis, thus providing basis of developing curcumin as a therapeutic agent for tumors. CRANAD-3 is designed from the curcumin skeleton as a near infrared (NIR) probe which exhibits potential for monitoring levels of Aβ species in vivo. Bexarotene is a retinoid X receptor (RXR) agonist, which has been approved as a drug for treatment of cancers. Studies have shown that bexarotene is capable of improving neuronal viability and diminishing Aβ burdens as well as side effects induced along with AD pathological progress. | en_US |
| dcterms.abstract | In chapter 2, hydrophilic modification was introduced to ZnPc and a conjugation strategy was adopted by linking ZnPc to curcumin, CRANAD-3 and bexarotene respectively. The ZnPc conjugates including ZnPcCur, ZnPcCRA and ZnPcBex were applied in inhibition study of Aβ fibrillization, which showed 24 hours' IC50 at 0.18, 0.23 and 0.27 µM compared to that of sym-ZnPc at 1.92 µM. In contrast, the candidates of metallic porphyrin-curcumin conjugates were not effective to inhibit the fibrillization process in similar time course. The results demonstrate the high potential of ZnPc conjugates in anti-amyloid research. | en_US |
| dcterms.abstract | Chapter 3 includes ZnPc analogues, i.e. sym-ZnPc, ZnPcCur, ZnPcCRA and ZnPcBex in developing anti-cancer therapies. Due to the conjugated small molecules, the fluorescence quantum yields and singlet oxygen quantum yields of these ZnPc conjugates could be biased. ZnPcCur and ZnPcCRA were found to colocalize with NPM1 while ZnPcBex showed lysosome targeting property, which may be responsible for their high cytotoxicity. ZnPcCur and ZnPcCRA showed cancer preference, which favors them with ideal properties for photodynamic cancer therapy. | en_US |
| dcterms.abstract | In chapter 4, metal binding ligand hydroxylmethyl substituted tris(2-picolyl)amine (HTPA) and TPA were linked to ZnPc analogue, favoring it property of chelating free metals. Upon binding to various transitional metal ions, ZnPc-TPA/HTPA showed variations in fluorescence emissions. The formed complexes, especially ZnPc-TPA/HTPA-Fe(II) and ZnPc-TPA/HTPA-Co(II) exhibited fluorescence turn-off effects towards H₂O₂ and superoxide respectively. Furthermore, ZnPc-TPA/HTPA-Co(II) showed well fitted dose dependent manner between fluorescence intensity and superoxide level, with IC50 at 15.65 and 23.55 µM respectively. As a pentadentate ligand, ZnPc-HTPA was found to induce alleviated cytotoxicity in cells. | en_US |
| dcterms.extent | 298 pages : color illustrations | en_US |
| dcterms.isPartOf | PolyU Electronic Theses | en_US |
| dcterms.issued | 2021 | en_US |
| dcterms.educationalLevel | Ph.D. | en_US |
| dcterms.educationalLevel | All Doctorate | en_US |
| dcterms.LCSH | Phthalocyanines | en_US |
| dcterms.LCSH | Hong Kong Polytechnic University -- Dissertations | en_US |
| dcterms.accessRights | open access | en_US |
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