Prajapati Rama, Garcia-Garrido Eduardo, Somoza Álvaro
Instituto Madrileño de Estudios Avanzados en Nanociencia (IMDEA Nanociencia), Faraday 9, 28049 Madrid, Spain.
Cancers (Basel). 2021 Jun 16;13(12):3011. doi: 10.3390/cancers13123011.
Albumin-based nanoparticles are an emerging platform for the delivery of various chemotherapeutics because of their biocompatibility, safety, and ease of surface modification for specific targeting. The most widely used method for the preparation of albumin nanoparticles is by desolvation process using glutaraldehyde (GLU) as a cross-linker. However, limitations of GLU like toxicity and interaction with drugs force the need for alternative cross-linkers. In the present study, several cross-linking systems were evaluated for the preparation of Bovine Serum Albumin (BSA) nanoparticles (ABNs) encapsulating Doxorubicin (Dox). Based on the results obtained from morphological characterization, in vitro release, and therapeutic efficacy in cells, N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP)-modified ABNs (ABN-SPDP) was chosen. Since ABN-SPDP are formed with disulfide linkage, the drug release is facilitated under a highly reducing environment present in the tumor sites. The cytotoxicity studies of those ABN-SPDP were performed in three different breast cell lines, highlighting the mechanism of cell death. The Dox-encapsulated ABN-SPDP showed toxicity in both the breast cancer cells (MCF-7 and MDA-MB-231), but, remarkably, a negligible effect was observed in non-tumoral MCF-10A cells. In addition to the hydrophilic Dox, this system could be used as a carrier for hydrophobic drugs like SN38. The system could be employed for the preparation of nanoparticles based on human serum albumin (HSA), which further enhances the feasibility of this system for clinical use. Hence, the albumin nanoparticles developed herein present an excellent potential for delivering various drugs in cancer therapy.
基于白蛋白的纳米颗粒因其生物相容性、安全性以及易于进行表面修饰以实现特异性靶向，成为一种新兴的多种化疗药物递送平台。制备白蛋白纳米颗粒最广泛使用的方法是采用戊二醛（GLU）作为交联剂的去溶剂化过程。然而，GLU存在毒性以及与药物相互作用等局限性，这促使人们需要寻找替代交联剂。在本研究中，评估了几种交联体系用于制备包封阿霉素（Dox）的牛血清白蛋白（BSA）纳米颗粒（ABNs）。基于形态表征、体外释放以及细胞治疗效果所获得的结果，选择了N - 琥珀酰亚胺基3 -（2 - 吡啶二硫基）丙酸酯（SPDP）修饰的ABNs（ABN - SPDP）。由于ABN - SPDP是通过二硫键形成的，在肿瘤部位存在的高还原环境下有利于药物释放。对这些ABN - SPDP进行了细胞毒性研究，研究在三种不同的乳腺癌细胞系中进行，突出了细胞死亡机制。包封Dox的ABN - SPDP在两种乳腺癌细胞（MCF - 7和MDA - MB - 231）中均显示出毒性，但值得注意的是，在非肿瘤性MCF - 10A细胞中观察到的影响可忽略不计。除了亲水性的Dox外，该体系还可作为疏水性药物如SN38的载体。该体系可用于制备基于人血清白蛋白（HSA）的纳米颗粒，这进一步提高了该体系临床应用的可行性。因此，本文开发的白蛋白纳米颗粒在癌症治疗中递送各种药物具有巨大潜力。
