ABSTRACT

Multifunctional nanocarriers have attracted considerable interest in improving cancer treatment outcomes. Poly(lactide-co-glycolide) (PLGA) nanospheres encapsulating copper oxide nanoparticles (CuO-NPs) are characterized by antitumor activity and exhibit dual-modal contrast-enhancing capabilities. An in vitro evaluation demonstrates that this delivery system allows controlled and sustained release of CuO-NPs. To achieve localized release on demand, an external stimulation by laser irradiation is suggested. Furthermore, to enable simultaneous complementary photothermal therapy, polydopamine (PDA) coating for augmented laser absorption is proposed. To this aim, two formulations of CuO-NPs loaded nanospheres are prepared from PLGA polymers RG-504 H (H-PLGA) and RG-502 H (L-PLGA) as scaffolds for surface modification through in situ polymerization of dopamine and then PEGylation. The obtained CuO-NPs-based multifunctional nanocarriers are characterized, and photothermal effects are examined as a function of wavelength and time. The results show that 808 nm laser irradiation of the coated nanospheres yields maximal temperature elevation (T = 41°C) and stimulates copper release at a much faster rate compared to non-irradiated formulations. Laser-triggered CuO-NP release is mainly depended on the PLGA core, resulting in faster release with L-PLGA, which also yielded potent anti-tumor efficacy in head and neck cancer cell line (Cal-33). In conclusion, the suggested multifunctional nanoplatform offers the integrated benefits of diagnostic imaging and laser-induced drug release combined with thermal therapy.

 抽象的

多功能纳米载体在改善癌症治疗效果方面引起了人们极大的兴趣。包裹氧化铜纳米颗粒 (CuO-NP) 的聚丙交酯乙交酯 (PLGA) 纳米球具有抗肿瘤活性，并表现出双模式对比度增强能力。体外评估表明，该递送系统可以控制和持续释放 CuO-NP。为了实现按需局部释放，建议通过激光照射进行外部刺激。此外，为了实现同步补充光热治疗，提出了用于增强激光吸收的聚多巴胺（PDA）涂层。为此，我们用 PLGA 聚合物 RG-504 H (H-PLGA) 和 RG-502 H (L-PLGA) 制备了两种负载 CuO-NPs 的纳米球配方，作为通过多巴胺原位聚合然后聚乙二醇化进行表面修饰的支架。对所获得的 CuO-NPs 基多功能纳米载体进行了表征，并检查了光热效应随波长和时间的变化。结果表明，与未照射的配方相比，808 nm 激光照射涂层纳米球可产生最大温度升高（T = 41°C），并以更快的速度刺激铜释放。激光触发的 CuO-NP 释放主要依赖于 PLGA 核心，导致 L-PLGA 释放更快，这在头颈癌细胞系 (Cal-33) 中也产生了有效的抗肿瘤功效。总之，所建议的多功能纳米平台提供了诊断成像和激光诱导药物释放与热疗法相结合的综合优势。