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用于在胶质瘤细胞系中双重递送阿霉素和吉非替尼的表面改性生物基聚合物纳米颗粒

Surface-Modified Biobased Polymeric Nanoparticles for Dual Delivery of Doxorubicin and Gefitinib in Glioma Cell Lines.

作者信息

Farheen Ms, Akhter Md Habban, Chitme Havagiray, Suliman Muath, Jaremko Mariusz, Emwas Abdul-Hamid

机构信息

School of Pharmaceutical and Population Health Informatics (SoPPHI), DIT University, Dehradun, Uttrakhand 248009, India.

Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha 62521, Saudi Arabia.

出版信息

ACS Omega. 2023 Jul 26;8(31):28165-28184. doi: 10.1021/acsomega.3c01375. eCollection 2023 Aug 8.

DOI:10.1021/acsomega.3c01375
PMID:37576633
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10413376/
Abstract

Glioma is a malignant form of brain cancer that is challenging to treat due to the progressive growth of glial cells. To target overexpressed folate receptors in glioma brain tumors, we designed and investigated doxorubicin-gefitinib nanoparticles (Dox-Gefit NPs) and folate conjugated Dox-Gefit NPs (Dox-Gefit NPs-F). Dox-Gefit NPs and Dox-Gefit NPs-F were characterized by multiple techniques including Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), proton nuclear magnetic resonance (H NMR), and transmission electron microscopy (TEM). In vitro release profiles were measured at both physiological and tumor endosomal pH. The cytotoxicity of the Dox-Gefit NP formulations was measured against C6 and U87 glioma cell lines. A hemolysis assay was performed to investigate biocompatibility of the formulations, and distribution of the drugs in different organs was also estimated. The Dox-Gefit NPs and Dox-Gefit NPs-F were 109.45 ± 7.26 and 120.35 ± 3.65 nm in size and had surface charges of -18.0 ± 3.27 and -20.0 ± 8.23 mV, respectively. Dox-Gefit NPs and Dox-Gefit NPs-F significantly reduced the growth of U87 cells, with IC values of 9.9 and 3.2 μM. Similarly, growth of the C6 cell line was significantly reduced, with IC values of 8.43 and 3.31 μM after a 24 h incubation, in Dox-Gefit NPs and Dox-Gefit NPs-F, respectively. The percentage drug releases of Dox and Gefit from Dox-Gefit NPs at pH 7.4 were 60.87 ± 0.59 and 68.23 ± 0.1%, respectively. Similarly, at pH 5.4, Dox and Gefit releases from NPs were 70.87 ± 0.28 and 69.24 ± 0.12%, respectively. Biodistribution analysis revealed that more Dox and Gefit were present in the brain than in the other organs. The functionalized NPs inhibited the growth of glioma cells due to high drug concentrations in the brain. Folate conjugated NPs of Dox-Gefit could be a treatment option in glioma therapy.

摘要

神经胶质瘤是一种恶性脑癌，由于神经胶质细胞的进行性生长，其治疗具有挑战性。为了靶向神经胶质瘤脑肿瘤中过表达的叶酸受体，我们设计并研究了阿霉素-吉非替尼纳米颗粒（Dox-Gefit NPs）和叶酸偶联的Dox-Gefit NPs（Dox-Gefit NPs-F）。通过多种技术对Dox-Gefit NPs和Dox-Gefit NPs-F进行了表征，包括傅里叶变换红外光谱（FT-IR）、X射线衍射（XRD）、差示扫描量热法（DSC）、质子核磁共振（H NMR）和透射电子显微镜（TEM）。在生理和肿瘤内体pH值下测量了体外释放曲线。测定了Dox-Gefit NP制剂对C6和U87神经胶质瘤细胞系的细胞毒性。进行了溶血试验以研究制剂的生物相容性，并估计了药物在不同器官中的分布。Dox-Gefit NPs和Dox-Gefit NPs-F的粒径分别为109.45±7.26和120.35±3.65 nm，表面电荷分别为-18.0±3.27和-20.0±8.23 mV。Dox-Gefit NPs和Dox-Gefit NPs-F显著降低了U87细胞的生长，IC值分别为9.9和3.2 μM。同样，在Dox-Gefit NPs和Dox-Gefit NPs-F中，孵育24小时后，C6细胞系的生长也显著降低，IC值分别为8.43和3.31 μM。在pH 7.4时，Dox-Gefit NPs中阿霉素和吉非替尼的药物释放百分比分别为60.87±0.59和68.23±0.1%。同样，在pH 5.4时，NPs中阿霉素和吉非替尼的释放率分别为70.87±0.28和69.24±0.12%。生物分布分析表明，脑中存在的阿霉素和吉非替尼比其他器官中的更多。由于脑中药物浓度高，功能化纳米颗粒抑制了神经胶质瘤细胞的生长。Dox-Gefit的叶酸偶联纳米颗粒可能是神经胶质瘤治疗的一种选择。

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