CICS-UBI - Centro de Investigação em Ciências da Saúde, Universidade da Beira Interior, 6200-506 Covilhã, Portugal.
CICS-UBI - Centro de Investigação em Ciências da Saúde, Universidade da Beira Interior, 6200-506 Covilhã, Portugal; CIEPQPF - Departamento de Engenharia Química, Universidade de Coimbra, 3030-790 Coimbra, Portugal.
Int J Pharm. 2021 May 1;600:120510. doi: 10.1016/j.ijpharm.2021.120510. Epub 2021 Mar 22.
Chemo-photothermal therapy (chemo-PTT) mediated by nanomaterials holds a great potential for cancer treatment. However, the tumor uptake of the systemically administered nanomaterials was recently found to be below 1%. To address this limitation, the development of injectable tridimensional polymeric matrices capable of delivering nanomaterials directly into the tumor site appears to be a promising approach. In this work, an injectable in situ forming ionotropically crosslinked chitosan-based hydrogel co-incorporating IR780 loaded nanoparticles (IR/BPN) and Doxorubicin (DOX) loaded nanoparticles (DOX/TPN) was developed for application in breast cancer chemo-PTT. The produced hydrogels (IR/BPN@Gel and IR/BPN+DOX/TPN@Gel) displayed suitable physicochemical properties and produced a temperature increase of about 9.1 °C upon exposure to Near Infrared (NIR) light. As importantly, the NIR-light exposure also increased the release of DOX from the hydrogel by 1.7-times. In the in vitro studies, the combination of IR/BPN@Gel with NIR light (photothermal therapy) led to a reduction in the viability of breast cancer cells to 35%. On the other hand, the non-irradiated IR/BPN+DOX/TPN@Gel (chemotherapy) only diminished cancer cells' viability to 85%. In contrast, the combined action of IR/BPN+DOX/TPN@Gel and NIR light reduced cancer cells' viability to about 9%, demonstrating its potential for breast cancer chemo-PTT.
纳米材料介导的化学-光热治疗（chemo-PTT）在癌症治疗方面具有巨大的潜力。然而，最近发现系统给药的纳米材料在肿瘤中的摄取量低于 1%。为了解决这一限制，开发能够将纳米材料直接递送到肿瘤部位的可注射三维聚合物基质似乎是一种很有前途的方法。在这项工作中，开发了一种可注射的原位形成的离子交联壳聚糖基水凝胶，共载有 IR780 负载的纳米颗粒（IR/BPN）和阿霉素（DOX）负载的纳米颗粒（DOX/TPN），用于乳腺癌的化学-PTT。所制备的水凝胶（IR/BPN@Gel 和 IR/BPN+DOX/TPN@Gel）具有合适的物理化学性质，并在近红外（NIR）光照射下产生约 9.1°C 的温升。同样重要的是，NIR 光照射也使水凝胶中 DOX 的释放增加了 1.7 倍。在体外研究中，IR/BPN@Gel 与 NIR 光（光热疗法）的联合作用将乳腺癌细胞的活力降低至 35%。另一方面，未辐照的 IR/BPN+DOX/TPN@Gel（化疗）仅将癌细胞的活力降低至 85%。相比之下，IR/BPN+DOX/TPN@Gel 和 NIR 光的联合作用将癌细胞的活力降低到了约 9%，证明了其在乳腺癌化学-PTT 中的潜力。
