https://scholars.lib.ntu.edu.tw/handle/123456789/598227
標題: | Keratin-Based Nanoparticles with Tumor-Targeting and Cascade Catalytic Capabilities for the Combinational Oxidation Phototherapy of Breast Cancer | 作者: | Lu T.-Y Lu W.-F Wang Y.-H Liao M.-Y Wei Y Fan Y.-J Chuang E.-Y Yu J. JIASHING YU |
關鍵字: | biomass human hair keratin;glutathione depletion;nitric oxide generation;photodynamic therapy;reactive nitrogen species;tumor targeting;Catalytic oxidation;Diseases;Nanoparticles;Nitric oxide;Photodynamic therapy;Photosensitizers;Tumors;Breast cancer cells;Catalytic capability;Phenylboronic acids;Photodynamic therapy (PDT);Targeting ligands;Therapeutic strategy;Tumor microenvironment;Tumor targeted delivery;Keratin;antineoplastic agent;keratin;nanoparticle;nitric oxide;animal;Bagg albino mouse;breast tumor;female;human;mouse;photochemotherapy;procedures;tumor cell line;Animals;Antineoplastic Agents;Breast Neoplasms;Cell Line, Tumor;Female;Humans;Keratins;Mice;Mice, Inbred BALB C;Nitric Oxide;Photochemotherapy | 公開日期: | 2021 | 卷: | 13 | 期: | 32 | 起(迄)頁: | 38074-38089 | 來源出版物: | ACS Applied Materials and Interfaces | 摘要: | Photodynamic therapy (PDT) holds tantalizing prospects of a prominent cancer treatment strategy. However, its efficacy remains limited by virtue of the hypoxic tumor microenvironment and the inadequate tumor-targeted delivery of photosensitizers, and these can be further exacerbated by the lack of development of a well-controlled nitric oxide (NO) release system at the target site. Inspired by Chinese medicine, we propose a revealing new keratin application. Keratin has garnered attention as an NO generator; however, its oncological use has rarely been investigated. We hypothesized that the incorporation of a phenylboronic acid (PBA) targeting ligand/methylene blue (MB) photosensitizer with a keratin NO donor would facilitate precise tumor delivery, enhancing PDT. Herein, we demonstrated that MB@keratin/PBA/d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) nanoparticles (MB@KPTNPs) specifically targeted breast cancer cells and effectively suppressed their growth. Through MB-mediated biometabolism, the endocytic MB@KPTNPs produced a sufficient amount of intracellular NO that reduced the glutathione level while boosting the efficiency of PDT. A therapeutic combination of NO/PDT was therefore achieved, resulting in significant inhibition of both in vivo tumor growth and lung metastasis. These findings underscore the importance of utilizing keratin-based nanoparticles that simultaneously combine targeting of the tumor and self-generating NO with a cascading catalytic ability as a novel oxidation therapeutic strategy for enhancing PDT. ? 2021 American Chemical Society. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85113780540&doi=10.1021%2facsami.1c10160&partnerID=40&md5=4cac2a18bcf17b12cf7aab471a2958d0 https://scholars.lib.ntu.edu.tw/handle/123456789/598227 |
ISSN: | 19448244 | DOI: | 10.1021/acsami.1c10160 |
顯示於: | 化學工程學系 |
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