He Lei, Javid Anbardan Zahra, Habibovic Pamela, van Rijt Sabine
Department of Instructive Biomaterials Engineering, MERLN Institute for Technology Inspired Regenerative Medicine, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
ACS Appl Nano Mater. 2024 Nov 1;7(22):25400-25411. doi: 10.1021/acsanm.4c04294. eCollection 2024 Nov 22.
Doxorubicin (Dox) is a promising anticancer chemotherapeutic, which has been widely investigated in osteosarcoma (OS) treatment. However, there are several disadvantages regarding its clinical use. Specifically, Dox has low specificity toward cancer cells, which can lead to serious side effects. In addition, cancer cells can develop resistance toward Dox, reducing its therapeutic efficiency. Combination therapy (CT) facilitated by nanoparticle delivery systems is a promising strategy to overcome these drawbacks. In this study, we investigated the effectiveness of Dox and selenium (Se) CT using mesoporous silica nanoparticles (MSN) coated with hyaluronic acid (HA) as drug carriers. We hypothesized that combining Se as a second agent can increase Dox anti-OS effectiveness and that MSN can be used to facilitate dual drug delivery. In our system, HA was used as a gatekeeper to control the intracellular release of Se/Dox by means of its pH-responsive degradation. CT therapy using MSNs coated with HA led to a higher OS inhibitory efficiency in vitro compared to MSNs carrying either Se or Dox alone. This study demonstrates that using MSNs for the dual delivery of Se and Dox is a promising method for OS therapy.
阿霉素（Dox）是一种很有前景的抗癌化疗药物，已在骨肉瘤（OS）治疗中得到广泛研究。然而，其临床应用存在一些缺点。具体而言，阿霉素对癌细胞的特异性较低，这可能导致严重的副作用。此外，癌细胞会对阿霉素产生耐药性，降低其治疗效果。由纳米颗粒递送系统辅助的联合疗法（CT）是克服这些缺点的一种有前景的策略。在本研究中，我们研究了以透明质酸（HA）包被的介孔二氧化硅纳米颗粒（MSN）作为药物载体的阿霉素与硒（Se）联合疗法的有效性。我们假设将硒作为第二种药物联合使用可以提高阿霉素对骨肉瘤的治疗效果，并且MSN可用于促进双药递送。在我们的系统中，HA用作“守门人”，通过其pH响应降解来控制硒/阿霉素的细胞内释放。与单独携带硒或阿霉素的MSN相比，使用HA包被的MSN进行联合疗法在体外对骨肉瘤具有更高的抑制效率。本研究表明，使用MSN进行硒和阿霉素的双药递送是骨肉瘤治疗的一种有前景的方法。
