Development of Novel Therapeutic Nanoplatform: Albumin-Gold Nanorods Based Core-Shell Nanoagent for Cancer Application

• Main Authors: Chiu, Hsien-Ting, 邱顯庭
• Other Authors: Huang, Yu-Fen
• Format: Others
• Language: en_US
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/967hrn

博士 === 國立清華大學 === 生醫工程與環境科學系 === 106 === Recently, the rapid development of albumin- and gold nanorod- based nanoplatforms has individually offered promising solutions for addressing numerous difficulties in cancer research. However, fabricating a hybrid nanocomposite comprising both albumin and gold nanorod with high quality, homogeneity and dispersity remains a great challenge nowadays. In this study, two robust and one-step synthesis, a direct glutaraldehyde (GTA) cross-linking and a new desolvation method were provided for the fabrication of a uniform core-shell gold nanorod/serum albumin nanoplatform (NR@SA). Interestingly, despite they have similar particle size, morphology and surface charge, it is surprisingly found that their behaviors are totally different in many perspectives. The cross-linked nanoparticles (NR@SAs, GTA) compared with denatured nanoparticles (NR@SAs, EM) preserves half-native characterizations, resulting in reducing protein corona formation, macrophage phagocytosis and enhancing tumor cell internalization; the other half-artificial properties strengthen the capability of drug loading/release and thermal transduction for photoacoustic imaging. The results provide the forefront and fundamental information at the interface of protein shell control for cancer theranostics. Furthermore, by conversely utilizing the aforementioned result of preference macrophage phagocytosis of NR@SAs (EM), nanoparticles-laden macrophage delivery system was successfully established. Instead of finding the best solution for chasing the maximum therapeutic efficacy, the bio-combination is aimed to dig in more basic investigations and discuss the importance of intratumoral drug homogeneity and retention ability in cancer therapy, because not just for those intravenous nano-drug delivery systems, nano/micro-particles for intratumoral therapy is also facing numerous difficulties such as uncontrollable injection site, uneven drug distribution and inefficient drug transportation, and the large dose requirement that is occasionally along with side effect, particularly in many clinical case. Our results demonstrated that the movable and drug-loading bio-reservoir compared with the pristine counterparts exerts the higher tumor coverage and prolongs drug retention time that can efficiently improve the therapeutic efficacy and minimize the possible adverse effect. By contrast, similar to the summaries in many clinical studies using intratumoral chemotherapy, injecting with the high dose of pristine nanoparticles not only displays limited therapeutic effect, but also leads to unhealable wounds and impair the quality of life. Overall, the two core-shell nanoparticles are devoted to a wide range study and understanding from fundamental research in biomaterial science to in vivo drug delivery application against cancer. Hopefully, this new discovery and related discussions will bring promising benefits in nanoparticle development for cancer theranostics.