Almohazey Dana, Ravinayagam Vijaya, Dafalla Hatim, Balasamy Rabindran Jermy
Department of Stem Cell Research, Institute for Research and Medical Consultations, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia.
Deanship of Scientific Research, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia.
Pharmaceutics. 2025 May 9;17(5):631. doi: 10.3390/pharmaceutics17050631.
: Nanocarrier particle design for treating chronic pulmonary diseases presents several challenges, including anatomical and physiological barriers. Drug-repurposing technology using monodispersed spherical silica is one of the innovative ways to deliver drugs. In the present study, the anticancer potential of combinational cisplatin/ribavirin was explored for targeted lung cancer therapeutics. : Monodispersed spherical silica (80 nm) capable of diffusing into the tracheal mucus region was chosen and doped with 10 wt% superparamagnetic iron oxide nanoparticles (SPIONs). Subsequently, it was wrapped with chitosan (Chi, 0.6 wt/vol%), functionalized with 5% wt/wt cisplatin (Cp)/ribavarin (Rib) and angiotensin-converting enzyme 2 (ACE-2) (1.0 μL/mL). Formulations are based on monodispersed spherical silica or halloysite and are termed as (S/MSSiO/Chi/Cp/Rib) or (S/Hal/Chi/Cp/Rib), respectively. : X-ray diffraction (XRD) and diffuse reflectance UV-visible spectroscopy (DRS-UV-vis) analysis of S/MSSiO/Chi/Cp/Rib confirmed the presence of SPION nanoclusters on the silica surface (45% coverage). The wrapping of chitosan on the silica was confirmed with a Fourier transformed infrared (FTIR) stretching band at 670 cm and ascribed to the amide group of the polymer. The surface charge by zetasizer and saturation magnetization by vibrating sample magnetometer (VSM) were found to be -15.3 mV and 8.4 emu/g. The dialysis membrane technique was used to study the Cp and Rib release between the tumor microenvironment and normal pH ranges from 5.5 to 7.4. S/MSSiO/Chi formulation demonstrated pH-responsive Cp and Rib at acidic pH (5.6) and normal pH (7.4). Cp and Rib showed release of ~27% and ~17% at pH 5.6, which decreases to ~14% and ~3.2% at pH 7.4, respectively. To assess the compatibility and cytotoxic effect of our nanocomposites, the cell viability assay (MTT) was conducted on cancer lung cells A549 and normal HEK293 cells. : The study shows that the designed nanoformulations with multifunctional capabilities are able to diffuse into the lung cells bound with dual drugs and the ACE-2 receptor.
用于治疗慢性肺部疾病的纳米载体颗粒设计面临诸多挑战，包括解剖学和生理学障碍。使用单分散球形二氧化硅的药物再利用技术是给药的创新方法之一。在本研究中，探索了顺铂/利巴韦林联合用药对肺癌的靶向治疗潜力。：选择能够扩散到气管黏液区域的80纳米单分散球形二氧化硅，并掺杂10重量%的超顺磁性氧化铁纳米颗粒（SPIONs）。随后，用壳聚糖（Chi，0.6重量/体积%）包裹，用5%重量/重量的顺铂（Cp）/利巴韦林（Rib）和血管紧张素转换酶2（ACE-2）（1.0微升/毫升）进行功能化。制剂基于单分散球形二氧化硅或埃洛石，分别称为（S/MSSiO/Chi/Cp/Rib）或（S/Hal/Chi/Cp/Rib）。：对S/MSSiO/Chi/Cp/Rib进行的X射线衍射（XRD）和漫反射紫外-可见光谱（DRS-UV-vis）分析证实了二氧化硅表面存在SPION纳米团簇（覆盖率45%）。壳聚糖在二氧化硅上的包裹通过670厘米处的傅里叶变换红外（FTIR）拉伸带得到证实，归因于聚合物的酰胺基团。通过zeta电位仪测得的表面电荷和通过振动样品磁强计（VSM）测得的饱和磁化强度分别为-15.3毫伏和8.4电磁单位/克。采用透析膜技术研究了肿瘤微环境与pH值在5.5至7.4之间的正常环境中Cp和Rib的释放情况。S/MSSiO/Chi制剂在酸性pH值（5.6）和正常pH值（7.4）下表现出对Cp和Rib的pH响应性。Cp和Rib在pH 5.6时的释放率分别约为27%和约17%，在pH 7.4时分别降至约14%和约3.2%。为了评估我们的纳米复合材料的相容性和细胞毒性作用，对肺癌细胞A549和正常HEK293细胞进行了细胞活力测定（MTT）。：研究表明，所设计的具有多功能能力的纳米制剂能够扩散到与双药和ACE-2受体结合的肺细胞中。
