Young Sarah A E, Muthami Joy, Pitcher Mica, Antovski Petar, Wamea Patricia, Murphy Robert Denis, Haghniaz Reihaneh, Schmidt Andrew, Clark Samuel, Khademhosseini Ali, Sheikhi Amir
Department of Bioengineering, University of California, Los Angeles, 410 Westwood Plaza, Los Angeles, CA 90095, USA.
Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, 570 Westwood Plaza, Los Angeles, CA 90095, USA.
Mater Today Chem. 2022 Mar;23. doi: 10.1016/j.mtchem.2021.100711. Epub 2021 Dec 30.
Cancer is one of the leading causes of death worldwide, affecting millions of people every year. While chemotherapy remains one of the most common cancer treatments in the world, the severe side effects of chemotherapy drugs impose serious concerns to cancer patients. In many cases, the chemotherapy can be localized to maximize the drug effects; however, the drug systemic circulation induces undesirable side effects. Here, we have developed a highly efficient cellulose-based nanoadsorbent that can capture more than 6000 mg of doxorubicin (DOX), one of the most widely used chemotherapy drugs, per gram of the adsorbent at physiological conditions. Such drug capture capacity is more than 3200% higher than other nanoadsorbents, such as DNA-based platforms. We show how anionic hairy cellulose nanocrystals, also known as electrosterically stabilized nanocrystalline cellulose (ENCC), bind to positively charged drugs in human serum and capture DOX immediately without imposing any cytotoxicity and hemolytic effects. We elucidate how ENCC provides a remarkable platform for biodetoxification at varying pH, ionic strength, ion type, and protein concentration. The outcome of this research may pave the way for developing the next generation and drug capture additives and devices.
癌症是全球主要死因之一,每年影响数百万人。虽然化疗仍然是世界上最常见的癌症治疗方法之一,但化疗药物的严重副作用给癌症患者带来了严重担忧。在许多情况下,化疗可以局部进行以最大化药物效果;然而,药物的全身循环会引发不良副作用。在此,我们开发了一种高效的纤维素基纳米吸附剂,在生理条件下,每克吸附剂可捕获超过6000毫克阿霉素(DOX),阿霉素是使用最广泛的化疗药物之一。这种药物捕获能力比其他纳米吸附剂(如基于DNA的平台)高出3200%以上。我们展示了阴离子型毛状纤维素纳米晶体,也称为静电稳定纳米晶纤维素(ENCC),如何在人血清中与带正电荷的药物结合并立即捕获DOX,且不会产生任何细胞毒性和溶血作用。我们阐明了ENCC如何在不同的pH值、离子强度、离子类型和蛋白质浓度下为生物解毒提供一个卓越的平台。这项研究的成果可能为开发下一代药物捕获添加剂和装置铺平道路。