Moloudi Kave, Abrahamse Heidi, George Blassan P
Laser Research Centre (LRC), Faculty of Health Sciences, Doornfontein Campus, 2028, University of Johannesburg, Johannesburg, South Africa.
Biochem Biophys Rep. 2024 Nov 17;40:101877. doi: 10.1016/j.bbrep.2024.101877. eCollection 2024 Dec.
Application of liposomes is a critical strategy in drug delivery and increase cellular uptake of drugs having low water solubility. Berberine (BBR) is a bioactive compound found in several plants, including Goldenseal, Barberry, and Oregon grape. It has garnered attention for its various health benefits, particularly in metabolic health and antimicrobial activity. However, one of the challenges associated with BBR is its water solubility. Moreover, BBR has photosensitizing potential via absorbance of light and generation of free radicals. Hence, to improve water solubility and bioavailability, one of the important strategies employed is using lipid-based carriers to enhance solubility. In this study we employed liposomes to deliver BBR in A549 lung cancer spheroid cells to enhance photodynamic therapy efficacies. Results from the EDS and UV-Vis spectroscopy revealed that the BBR had been loaded onto liposomes, with three peaks appearing between 250 and 450 nm. Morphology of Lipo@BBR nanocomplex was in wavy crest shape and the size was 56.99 ± 3.74 nm in SEM and TEM analysis, respectively. FTIR data illustrated that Lipo@BBR has four significant peaks at 1250, 1459, 1736, and 2907 cm. DLS data showed that Lipo@BBR has a negative surface charge with a -10.7 Zeta Potential (mV). Additionally, based on Zetasizer measurements, the size of Lipo@BBR complex was 82.7 ± 6.5. Cytotoxicity assay investigation with MTT assay presented that IC of Lipo@BBR in PDT was 10 ± 0.5 μg/mL that led to a volume reduction of the A549 spheroids after five sessions of PDT fractionation (total light dose was set at 25 J/cm). qPCR and immunofluorescence results demonstrated that Lipo@BBR increases the BAX/BCL2 ratio in A549 spheroid cells, hence improving PDT efficiency. In conclusion, our results illustrated that safe dose of Lipo@BBR (10 ± 0.5 μg/mL) in PDT fractionation protocol can be one of the strategies to suppress the tumor volume and cell death proliferation. Authors recommend using Lipo@BBR nanocomplex in PDT fractionation as well as more investigation is warranted.
脂质体的应用是药物递送中的一项关键策略，可提高低水溶性药物的细胞摄取率。黄连素（BBR）是一种存在于多种植物中的生物活性化合物，包括白毛茛、伏牛花和俄勒冈葡萄。它因其多种健康益处而受到关注，特别是在代谢健康和抗菌活性方面。然而，与BBR相关的挑战之一是其水溶性。此外，BBR通过吸收光和产生活性自由基具有光敏潜力。因此，为了提高水溶性和生物利用度，采用的重要策略之一是使用基于脂质的载体来提高溶解度。在本研究中，我们使用脂质体将BBR递送至A549肺癌球状体细胞中，以提高光动力疗法的疗效。能谱分析（EDS）和紫外可见光谱（UV-Vis）的结果表明，BBR已负载到脂质体上，在250至450nm之间出现三个峰。在扫描电子显微镜（SEM）和透射电子显微镜（TEM）分析中，Lipo@BBR纳米复合物的形态呈波峰状，尺寸分别为56.99±3.74nm。傅里叶变换红外光谱（FTIR）数据表明，Lipo@BBR在1250、1459、1736和2907cm处有四个显著峰。动态光散射（DLS）数据表明，Lipo@BBR带负表面电荷，zeta电位为-10.7mV。此外，基于纳米粒度分析仪的测量，Lipo@BBR复合物的尺寸为82.7±6.5。用MTT法进行的细胞毒性试验研究表明，Lipo@BBR在光动力疗法中的半数抑制浓度（IC）为10±0.5μg/mL，在五次光动力疗法分次治疗后导致A549球状体体积减小（总光剂量设定为25J/cm）。定量聚合酶链反应（qPCR）和免疫荧光结果表明，Lipo@BBR增加了A549球状体细胞中的BAX/BCL2比值，从而提高了光动力疗法的效率。总之，我们的结果表明，在光动力疗法分次治疗方案中，安全剂量的Lipo@BBR（10±0.5μg/mL）可以是抑制肿瘤体积和细胞死亡增殖的策略之一。作者建议在光动力疗法分次治疗中使用Lipo@BBR纳米复合物，并且有必要进行更多的研究。
