Preparation and characterization of RGD modified “core-shell” nanoparticles loaded with doxorubicin and study on their anti-tumor effects

LI Qingling; LIU Jinguang; ZU Qi; YU Qinglong; SUN Shizhen

doi:10.6039/j.issn.1001-0408.2025.16.11

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Preparation and characterization of RGD modified “core-shell” nanoparticles loaded with doxorubicin and study on their anti-tumor effects

更新时间：2025-09-25

- Preparation and characterization of RGD modified “core-shell” nanoparticles loaded with doxorubicin and study on their anti-tumor effects
- ZHONGGUO YAOFANG Vol. 36, Issue 16, Pages: 2017-2023(2025)
- 作者机构：
  
  1.山东中医药高等专科学校中医系，山东烟台　264199
  2.烟台药物研究所，山东烟台　264000
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2025.16.11
  CLC： R943;R979.1
- Received：12 February 2025，
  
  Revised：2025-07-07，
  
  Accepted：10 July 2025，
  
  Published：30 August 2025
- 稿件说明：
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李庆龄,刘金光,祖琦,等.RGD修饰的载多柔比星“核-壳”型纳米粒的制备、表征及其抗肿瘤作用研究[J].中国药房,2025,36(16):2017-2023.

LI Qingling,LIU Jinguang,ZU Qi,et al.Preparation and characterization of RGD modified “core-shell” nanoparticles loaded with doxorubicin and study on their anti-tumor effects[J].ZHONGGUO YAOFANG,2025,36(16):2017-2023.
李庆龄,刘金光,祖琦,等.RGD修饰的载多柔比星“核-壳”型纳米粒的制备、表征及其抗肿瘤作用研究[J].中国药房,2025,36(16):2017-2023. DOI： 10.6039/j.issn.1001-0408.2025.16.11.

LI Qingling,LIU Jinguang,ZU Qi,et al.Preparation and characterization of RGD modified “core-shell” nanoparticles loaded with doxorubicin and study on their anti-tumor effects[J].ZHONGGUO YAOFANG,2025,36(16):2017-2023. DOI： 10.6039/j.issn.1001-0408.2025.16.11.

摘要

目的

制备精氨酰-甘氨酰-天冬氨酸（RGD）修饰的载多柔比星（DOX）“核-壳”型纳米粒（RGD@DOX-LPNs），并对其进行表征和抗肿瘤作用研究。

方法

通过纳米沉淀法制备RGD@DOX-LPNs，观察其外观和微观形态，检测其粒径、多分散性指数（PDI）、Zeta电位，并进行差示扫描量热、X射线衍射分析，检测其包封率和载药量，考察其稳定性，分析其体外释放情况、体外黏液扩散情况和肿瘤细胞摄取情况[以香豆素6（COU）定位]、体内组织分布及胃肠道滞留情况[以11-氯-1，1′-二正丙基-3，3，3′，3′-四甲基-10，12-三亚甲基吲哚三碳花青碘盐（IR780）定位]。以4T1荷瘤小鼠为对象，评价所得制剂对其瘤体体积、瘤重、细胞凋亡率的影响。

结果

所制RGD@DOX-LPNs为橙色透明液体，其颗粒大小均一且近球形；纳米粒粒径为（159.67±8.02）nm，PDI为0.15±0.06，Zeta电位为（－19.70±0.79）mV；经RDG修饰后，DOX的热吸收峰和晶型衍射峰均消失；RGD@DOX-LPNs

的包封率为（72.65±4.37）%，载药量为（4.62±0.38）%；于4、25 ℃下放置7 d后的外观、粒径、包封率均无明显变化；其4 h的累积释放量约为73%，低于DOX原料药（1 h内近乎释放完全）；COU-LPNs第1段薄片中COU的量显著低于同段RGD@COU-LPNs，而第2～5段薄片中COU的量则显著高于RGD@COU-LPNs（

＜0.01）；肠细胞对RGD@COU-LPNs中COU的摄取量明显多于COU-LPNs（

＜0.05）；RGD@IR780-LPNs的离体组织荧光强度均强于IR780-LPNs，且显示出更强的胃肠道滞留性。与DOX原料药及普通纳米粒（DOX-LPNs）比较，RGD@DOX-LPNs的抑瘤率更高（65.74%），并可使荷瘤小鼠瘤体体积显著缩小、瘤重显著降低、细胞凋亡率显著升高（

＜0.01）。

结论

成功制备了RGD@DOX-LPNs；该制剂具有一定的缓释作用，可增加肠细胞对DOX的摄取，增强DOX的胃肠道黏液滞留性和抗乳腺癌活性。

Abstract

OBJECTIVE

To prepare Arg-Gly-Asp（RGD）-modified doxorubicin （DOX）-loaded “core-shell” nanoparticles （RGD@DOX-LPNs）， characterize the nanoparticles， and investigate their antitumor effects.

METHODS

RGD@DOX-LPNs were prepared using the nanoprecipitation method. Their morphology was examined by visual inspection and electron microscopy. Particle size， polydispersity index （PDI）， and Zeta potential were determined， and differential scanning calorimetry （DSC） and X-ray diffraction （XRD） were employed. Encapsulation efficiency （EE）， drug loading （DL）， and stability were evaluated. The

in vitro

release kinetics， mucus diffusion， and tumor cell uptake [tracked using coumarin 6 （COU）

]

were investigated. The

in vivo

tissue distribution and gastrointestinal retention [labeled with 11-chloro-1，1′-dipropyl-3，3，3′，3′-tetramethyl-10，12-trimethyleneindotricarbocyanine iodide （IR780）

]

were investigated. Using 4T1 tumor-bearing mice as the experimental subjects， the effects of the prepared formulation on tumor volume， tumor weight， and cell apoptosis rate were evaluated.

RESULTS

RGD@DOX-LPNs presented as orange transparent liquid with uniform and near-spherical particles. The particle size was （159.67±8.02） nm， PDI was 0.15±0.06， and Zeta potential was （－19.70±0.79） mV. After modification with RGD， the thermal absorption pea

k and crystalline diffraction peak of DOX disappeared. EE and DL of RGD@DOX-LPNs were （72.65±4.37）% and （4.62±0.38）%， respectively. No obvious changes in appearance， particle size， or EE were observed after storage at 4 ℃ and 25 ℃ for 7 days. The cumulative drug release at 4 h was approximately 73%， which was lower than that of free DOX （almost completely released within 1 h）. The amount of COU in the first segmental mucus layer of COU-LPNs was significantly lower than that in the corresponding segment of RGD@COU-LPNs， whereas it was significantly higher in the 2nd to 5th segmental mucus layers compared to RGD@COU-LPNs （

＜0.01）. Cellular uptake of RGD@COU-LPNs was significantly higher than that of COU-LPNs（

＜0.05）. The isolated tissue fluorescence intensity of RGD@IR780-LPNs was stronger than that of IR780-LPNs， indicating better small intestinal retention. Compared with free DOX and unmodified nanoparticles （DOX-LPNs）， RGD@DOX-LPNs exhibited a higher tumor inhibition rate of 65.74%， significantly reduced tumor volume and weight， and increased apoptosis rate（

＜0.01）.

CONCLUSIONS

RGD@DOX-LPNs are successfully prepared with sustained release properties， which can improve gastrointestinal mucus retention， enhance cellular uptake of DOX， and have potent antitumor activity against breast cancer.

关键词

Keywords

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