Aina Toyin, Salifu Ali A, Kizhakkepura Sonu, Danyuo Yiporo, Obayemi John D, Oparah Josephine C, Ezenwafor Theresa C, Onwudiwe Killian C, Ani Chukwuemeka J, Biswas Suchi S, Onyekanne Chinyerem, Odusanya Olushola S, Madukwe Jonathan, Soboyejo Winston O
Department of Materials Science and Engineering, African University of Science and Technology, Abuja, Nigeria.
Department of Mechanical and Materials Engineering, Worcester Polytechnic Institute, Worcester, Massachusetts, USA.
J Biomed Mater Res B Appl Biomater. 2023 Mar;111(3):665-683. doi: 10.1002/jbm.b.35185. Epub 2022 Oct 31.
This article presents silica nanoparticles for the sustained release of AMACR antibody-conjugated and free doxorubicin (DOX) for the inhibition of prostate cancer cell growth. Inorganic MCM-41 silica nanoparticles were synthesized, functionalized with phenylboronic acid groups (MCM-B), and capped with dextran (MCM-B-D). The nanoparticles were then characterized using Fourier-transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, zeta potential analysis, nitrogen sorption, X-ray diffraction, and thermogravimetric analysis, before exploring their potential for drug loading and controlled drug release. This was done using a model prostate cancer drug, DOX, and a targeted prostate cancer drug, α-Methyl Acyl-CoA racemase (AMACR) antibody-conjugated DOX, which attaches specifically to AMACR proteins that are overexpressed on the surfaces of prostate cancer cells. The kinetics of sustained drug release over 30 days was then studied using zeroth order, first order, second order, Higuchi, and the Korsmeyer-Peppas models, while the thermodynamics of drug release was elucidated by determining the entropy and enthalpy changes. The flux of the released DOX was also simulated using the COMSOL Multiphysics software package. Generally, the AMACR antibody-conjugated DOX drug-loaded nanoparticles were more effective than the free DOX drug-loaded formulations in inhibiting the growth of prostate cancer cells in vitro over a 96 h period. The implications of the results are then discussed for the development of drug-eluting structures for the localized and targeted treatment of prostate cancer.
本文介绍了用于持续释放AMACR抗体偶联的阿霉素（DOX）和游离阿霉素以抑制前列腺癌细胞生长的二氧化硅纳米颗粒。合成了无机MCM-41二氧化硅纳米颗粒，用苯硼酸基团进行功能化（MCM-B），并用葡聚糖封端（MCM-B-D）。在探索其药物负载和控释潜力之前，使用傅里叶变换红外光谱、扫描电子显微镜、透射电子显微镜、zeta电位分析、氮吸附、X射线衍射和热重分析对纳米颗粒进行了表征。这是通过使用一种前列腺癌模型药物DOX和一种靶向前列腺癌药物——α-甲基酰基辅酶A消旋酶（AMACR）抗体偶联的DOX来完成的，该药物能特异性地附着在前列腺癌细胞表面过度表达的AMACR蛋白上。然后使用零级、一级、二级、Higuchi和Korsmeyer-Peppas模型研究了30天内药物持续释放的动力学，同时通过确定熵和焓的变化来阐明药物释放的热力学。还使用COMSOL Multiphysics软件包模拟了释放的DOX的通量。一般来说，在96小时的体外实验中，负载AMACR抗体偶联DOX的纳米颗粒在抑制前列腺癌细胞生长方面比负载游离DOX的制剂更有效。随后讨论了这些结果对开发用于前列腺癌局部和靶向治疗的药物洗脱结构的意义。
