纳米技术带来了药物设计的重大进步,预防革命,诊断,治疗各种疾病。纳米技术的战略利用,以提高药物负荷,delivery,释放引起了越来越多的关注,利用这些系统提供的增强的物理和化学性质。聚酰胺胺(PAMAM)树枝状聚合物在药物递送中至关重要,然而,还有进一步加强的空间。在这项研究中,我们将PAMAM树枝状聚合物与壳聚糖(CS)缀合以增强肿瘤细胞的细胞内化。具体来说,最初将多柔比星(DOX)加载到PAMAM树枝状聚合物中以通过分子间力形成DOX加载的PAMAM(DOX@PAMAM)复合物。随后,将CS连接到负载DOX的PAMAM树枝状聚合物上,以通过希夫碱反应通过戊二醛交联产生负载DOX的CS缀合的PAMAM(DOX@CS@PAMAM)。使用傅里叶变换红外(FTIR)光谱对所得DOX@CS@PAMAM配合物进行了全面表征,透射电子显微镜(TEM),和动态光散射(DLS)。值得注意的是,而在酸性环境中DOX@CS@PAMAM的药物释放曲线不如DOX@PAMAM,DOX@CS@PAMAM证明了有效的酸响应药物释放,在25小时内累积释放70%归因于亚胺键。最重要的是,与DOX@PAMAM相比,DOX@CS@PAMAM表现出显著的选择性细胞内化速率和抗肿瘤功效,通过细胞活力试验验证,荧光成像,和流式细胞术分析。总之,DOX@CS@PAMAM与未结合的PAMAM树枝状聚合物相比,具有优异的抗肿瘤作用,从而扩大了基于树枝状聚合物的纳米药物的范围,具有增强的治疗功效和在癌症治疗中的有希望的应用。
Nanotechnology has ushered in significant advancements in drug design, revolutionizing the prevention, diagnosis, and treatment of various diseases. The strategic utilization of nanotechnology to enhance drug loading, delivery, and release has garnered increasing attention, leveraging the enhanced physical and chemical properties offered by these systems. Polyamidoamine (PAMAM) dendrimers have been pivotal in drug delivery, yet there is room for further enhancement. In this study, we conjugated PAMAM dendrimers with chitosan (CS) to augment cellular internalization in tumor cells. Specifically, doxorubicin (DOX) was initially loaded into
PAMAM dendrimers to form DOX-loaded
PAMAM (DOX@
PAMAM) complexes via intermolecular forces. Subsequently, CS was linked onto the DOX-loaded
PAMAM dendrimers to yield CS-conjugated
PAMAM loaded with DOX (DOX@CS@PAMAM) through glutaraldehyde crosslinking via the Schiff base reaction. The resultant DOX@CS@PAMAM complexes were comprehensively characterized using Fourier-transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering (DLS). Notably, while the drug release profile of DOX@CS@PAMAM in acidic environments was inferior to that of DOX@
PAMAM, DOX@CS@
PAMAM demonstrated effective acid-responsive drug release, with a cumulative release of 70% within 25 h attributed to the imine linkage. Most importantly, DOX@CS@PAMAM exhibited significant selective cellular internalization rates and antitumor efficacy compared to DOX@PAMAM, as validated through cell viability assays, fluorescence imaging, and flow cytometry analysis. In summary, DOX@CS@
PAMAM demonstrated superior antitumor effects compared to unconjugated
PAMAM dendrimers, thereby broadening the scope of dendrimer-based nanomedicines with enhanced therapeutic efficacy and promising applications in cancer therapy.