用于药物靶向递送与免疫激活的智能多肽的研究

蒙然; 林彦彤; 姚炜钦; 张诗曼; 陈巍海; 张先正

doi:10.11777/j.issn1000-3304.2025.25052

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用于药物靶向递送与免疫激活的智能多肽的研究

研究论文 | 更新时间：2025-05-19

- 用于药物靶向递送与免疫激活的智能多肽的研究
- Research on Smart Peptides for Drug Targeted Delivery and Immune Activation
- 高分子学报 2025年页码：1-12
- 作者机构：
  
  武汉大学化学与分子科学学院生物医用高分子材料教育部重点实验室武汉 430072
- 作者简介：
  
  E-mail: chenweihai@whu.edu.cn;
  E-mail:; xz-zhang@whu.edu.cn
- 基金信息：
  
  国家自然科学基金(52273301;52473145;22135005)
- DOI：10.11777/j.issn1000-3304.2025.25052
  中图分类号：
- CSTR：32057.14.GFZXB.2025.7389
- 收稿日期：2025-02-27，
  
  录用日期：2025-03-25，
  
  网络出版日期：2025-05-19，
- 稿件说明：
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蒙然, 林彦彤, 姚炜钦, 张诗曼, 陈巍海, 张先正. 用于药物靶向递送与免疫激活的智能多肽的研究. 高分子学报, doi: 10.11777/j.issn1000-3304.2025.25052

Meng, R.; Lin, Y. T.; Yao, W. Q.; Zhang, S. M.; Chen, W. H.; Zhang, X. Z. Research on smart peptides for drug targeted delivery and immune activation. Acta Polymerica Sinica, doi: 10.11777/j.issn1000-3304.2025.25052
蒙然, 林彦彤, 姚炜钦, 张诗曼, 陈巍海, 张先正. 用于药物靶向递送与免疫激活的智能多肽的研究. 高分子学报, doi: 10.11777/j.issn1000-3304.2025.25052 DOI： CSTR： 32057.14.GFZXB.2025.7389.

Meng, R.; Lin, Y. T.; Yao, W. Q.; Zhang, S. M.; Chen, W. H.; Zhang, X. Z. Research on smart peptides for drug targeted delivery and immune activation. Acta Polymerica Sinica, doi: 10.11777/j.issn1000-3304.2025.25052 DOI： CSTR： 32057.14.GFZXB.2025.7389.

摘要

设计开发了一种多肽纳米药物(RGDGPN@DOX)，以实现药物靶向递送和增强免疫应答，提高肿瘤治疗的精确性和有效性. 其中，精氨酸-甘氨酸-天冬氨酸(RGD)肽段能够特异性靶向肿瘤细胞高表达的整合素，增强纳米药物在肿瘤部位的富集和摄取；脯氨酸-亮氨酸-甘氨酸-亮氨酸-丙氨酸(PLGLA)肽段则具备对基质金属蛋白酶2(MMP2)的响应特性，能够在肿瘤微环境中选择性释放化疗药物阿霉素(DOX)，提高化疗疗效同时减少对正常组织的毒副作用；而

-甲酰基-蛋氨酸-亮氨酸-苯丙氨酸(NFMLP)的引入赋予了纳米药物免疫调节的功能，促进巨噬细胞的募集及激活，进一步增强抗肿瘤效果. 体外细胞实验结果表明，RGDGPN@DOX多肽纳米药物能够精准杀灭肿瘤细胞，诱导免疫反应，促进巨噬细胞的趋化，在药物靶向递送和免疫治疗领域具有良好的应用潜力.

Abstract

Traditional chemotherapeutic drugs lack targeting ability and often cause damage to normal tissues during treatment. With advancements in tumor research

the development of intelligent drug delivery systems has made remarkable progress. Peptides are widely used in the fields of drug delivery and bioimaging because of their unique biological activity

favorable biocompatibility

ease of synthesis

modification

and functionalization. In this study

a peptide nanomedicine (RGDGPN@DOX) was rationally designed to achieve precise tumor-targeted drug delivery

amplify immune activation

and enhance therapeutic efficacy. Among them

the RGD peptide could specifically target overexpressed integrins in tumor cells and enhance the enrichment and uptake of nanomedicines in tumor cells. Furthermore

the response characteristic of the PLGLA segment was matrix metalloproteinase 2 (MMP2)

which selectively released the chemotherapeutic drug doxorubicin (DOX) in the tumor microenvironment. Simultaneously

the incorporation of the NFMLP peptide endowed the nanomedicine with immune-regulatory capabilities

promoting the recruitment and activation of macrophages and further enhancing the antitumor effect. The results of the cell experiments demonstrated that RGDGPN@DOX peptide nanodrugs could accurately target tumor cells and effectively kill tumor cells. It also induces an immune response

promotes macrophage chemotaxis

and enhances antitumor immune effects. The designed RGDGPN@DOX peptide nanodrugs integrate multiple functions

including targeting

enzyme-responsive release

chemotherapy

and immunomodulation

showing promising application potential in the fields of drug-targeted delivery and immunotherapy.

关键词

Keywords

references

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