DryProTech Lab., Department of Chemical Engineering, Indian Institute of Technology Gandhinagar, Palaj, Gandhinagar, Gujarat 382055, India.
ACS Appl Bio Mater. 2024 Aug 19;7(8):5483-5495. doi: 10.1021/acsabm.4c00633. Epub 2024 Jul 24.
The research in nanotherapeutics is rapidly advancing, particularly in the realm of nanoconstructs for drug delivery. This study introduces folate-based carbon dot-decorated nanodroplets (f-D), synthesized from a binary mixture of negatively charged folic acid carbon dots (f-CDs) and cationic-branched polyethylenimine (PEI). The uniformly spherical nanodroplets with an average diameter of 115 ± 15 nm exhibit notable photoluminescence. Surface potential analysis reveals a significant change upon coacervation, attributed to strong electrostatic interactions between f-CD and PEI. The engineered nanodroplets show excellent colloidal and photostability even after 6 months of storage at room temperature. The pH-dependent self-assembly and disassembly properties of f-D are explored for drug loading and release studies using doxorubicin (DOX) as a model anticancer drug. Moreover, the f-D nanocarrier demonstrates significantly higher drug loading capabilities (∼90%). release studies of doxorubicin-loaded f-D [f-D] reveal 5 times higher drug release at lysosomal pH 5.4 compared to that at physiological blood pH 7.4. Cytocompatibility assessments using the MTT assay on HeLa, A549, and NIH-3T3 cells confirm the nontoxic nature of f-D, even at high concentrations. Additionally, f-D exhibits higher cytotoxicity in HeLa cells compared to f-CD at similar DOX concentrations. Cellular uptake studies show an increased uptake of f-D in folate receptor-positive HeLa and MDA-MB 231 cells. Hemolysis assay validated the biocompatibility of the developed formulation. Overall, these engineered nanodroplets represent a class of nontoxic nanocarriers that offer promising potential as nanotherapeutics for folate receptor-positive cells.
纳米治疗学的研究正在迅速发展，特别是在药物传递的纳米构建领域。本研究介绍了叶酸基碳点修饰的纳米液滴（f-D），它是由带负电荷的叶酸碳点（f-CDs）和阳离子支化聚乙烯亚胺（PEI）的二元混合物合成的。具有 115±15nm 平均直径的均匀球形纳米液滴表现出显著的光致发光。表面电势分析表明，在共凝聚时发生了显著变化，这归因于 f-CD 和 PEI 之间的强静电相互作用。即使在室温下储存 6 个月后，工程化的纳米液滴仍表现出优异的胶体和光稳定性。通过使用阿霉素（DOX）作为模型抗癌药物进行药物负载和释放研究，探索了 f-D 的 pH 依赖性自组装和解组装特性。此外，f-D 纳米载体表现出显著更高的药物负载能力（约 90%）。负载阿霉素的 f-D[f-D]的释放研究表明，在溶酶体 pH5.4 下的药物释放是在生理血液 pH7.4 下的 5 倍。使用 MTT 测定法在 HeLa、A549 和 NIH-3T3 细胞上进行的细胞相容性评估证实了 f-D 的非毒性，即使在高浓度下也是如此。此外，f-D 在类似 DOX 浓度下对 HeLa 细胞的细胞毒性高于 f-CD。细胞摄取研究表明，在叶酸受体阳性的 HeLa 和 MDA-MB231 细胞中，f-D 的摄取增加。溶血试验验证了所开发配方的生物相容性。总的来说，这些工程化的纳米液滴代表了一类无毒的纳米载体，作为叶酸受体阳性细胞的纳米治疗剂具有很大的应用潜力。
