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Research on Smart Peptides for Drug Targeted Delivery and Immune Activation
- Acta Polymerica Sinica Vol. 56, Issue 8, Pages: 1333-1344(2025)
- 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：
Wei-hai Chen, E-mail: chenweihai@whu.edu.cn
- 基金信息：
DOI：10.11777/j.issn1000-3304.2025.25052
CLC：- CSTR：32057.14.GFZXB.2025.7389
Received：27 February 2025，
Accepted：25 March 2025，
Published Online：17 June 2025，
Published：20 August 2025
- 稿件说明：
移动端阅览
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, 2025, 56(8), 1333-1344
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, 2025, 56(8), 1333-1344
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, 2025, 56(8), 1333-1344 DOI： 10.11777/j.issn1000-3304.2025.25052. 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, 2025, 56(8), 1333-1344 DOI： 10.11777/j.issn1000-3304.2025.25052. 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
N
-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
Wang S. ; Yang S. Q. ; Cui Z. L. ; Liu X. Y. ; Yang Y. ; Wang T. ; Ma W. J. ; Zhou Y. B. ; Liang R. Z. ; Yan D. ; Chen H. Z. In-situ activation of CuAl-LDH nanosheets to catalyze bioorthogonal chemistry in vivo in tumor microenvironment for precise chemotherapy and chemodynamic therapy . Chem. Eng. J. , 2023 , 457 , 141186 . doi: 10.1016/j.cej.2022.141186 http://dx.doi.org/10.1016/j.cej.2022.141186
刘畅 , 陈宇欣 , 王江帆 , 罗萱 , 黄宇迪 , 徐瑾蕾 , 鄢国平 , 陈思 , 张先正 . 基于枝化多肽的多功能药物递送系统用于肿瘤细胞核的精准靶向治疗 . 高分子学报 , 2018 , ( 6 ), 682 - 691 . doi: 10.11777/j.issn1000-3304.2017.17335 http://dx.doi.org/10.11777/j.issn1000-3304.2017.17335
Cui W. ; Li J. B. ; Decher G. Self-assembled smart nanocarriers for targeted drug delivery . Adv. Mater. , 2016 , 28 ( 6 ), 1302 - 1311 . doi: 10.1002/adma.201502479 http://dx.doi.org/10.1002/adma.201502479
李怡静 , 龚雪峰 , 王冬 , 杨洲 , 曹晖 , 王磊 . 基于多肽的药物递送系统研究进展 . 高分子学报 , 2022 , 53 ( 5 ), 445 - 456 . doi: 10.11777/j.issn1000-3304.2021.21369 http://dx.doi.org/10.11777/j.issn1000-3304.2021.21369
Ramirez-Velez I. ; Namjoshi A. A. ; Effiong U. M. ; Peppas N. A. ; Belardi B. Paracellular delivery of protein drugs with smart EnteroPatho nanoparticles . ACS Nano , 2024 , 18 ( 32 ), 21038 - 21051 . doi: 10.1021/acsnano.4c02116 http://dx.doi.org/10.1021/acsnano.4c02116
吉垒 , 张雪豪 , 杨子欣 , 乔增莹 , 王浩 . 肿瘤微环境诱导多肽聚合物原位组装行为研究 . 高分子学报 , 2019 , 50 ( 6 ), 642 - 652 . doi: 10.11777/j.issn1000-3304.2019.19039 http://dx.doi.org/10.11777/j.issn1000-3304.2019.19039
Pan W. ; Zhang L. ; Li L. ; Cen J. ; Song R. ; Song C. ; Zhang G. ; Hu J. ; Liu S. Engineering semicarbazide-bearing polypeptide conjugates for efficient tumor chemotherapy and imaging of tumor metastasis . Adv Mater , 2024 , 36 ( 9 ), e 2309315 . doi: 10.1002/adma.202309315 http://dx.doi.org/10.1002/adma.202309315
Kim W. ; Thévenot J. ; Ibarboure E. ; Lecommandoux S. ; Chaikof E. L. Self-assembly of thermally responsive amphiphilic diblock copolypeptides into spherical micellar nanoparticles . Angew. Chem. Int. Ed , 2010 , 49 ( 25 ), 4257 - 4260 . doi: 10.1002/anie.201001356 http://dx.doi.org/10.1002/anie.201001356
Lampel A. Biology-inspired supramolecular peptide systems . Chem , 2020 , 6 ( 6 ), 1222 - 1236 . doi: 10.1016/j.chempr.2020.03.005 http://dx.doi.org/10.1016/j.chempr.2020.03.005
邱文秀 , 程翰 , 张先正 , 卓仁禧 . 刺激响应型多肽的研究及其在肿瘤诊疗中的应用 . 高分子学报 , 2018 , ( 1 ), 32 - 44 . doi: 10.11777/j.issn1000-3304.2018.17256 http://dx.doi.org/10.11777/j.issn1000-3304.2018.17256
Liu, J. Y.;, Shen, G. Z.;, Yan, X. H. ;. Bacterial systems as a precision delivery platform of therapeutic peptides for cancer therapy. Polym. Sci. Technol. , 2025 , polymscitech. 4 c 00026 . doi: 10.1021/polymscitech.4c00026 http://dx.doi.org/10.1021/polymscitech.4c00026
Liu Y. Y. ; Ran R. ; Chen J. T. ; Kuang Q. F. ; Tang J. ; Mei L. ; Zhang Q. Y. ; Gao H. L. ; Zhang Z. R. ; He Q. Paclitaxel loaded liposomes decorated with a multifunctional tandem peptide for glioma targeting . Biomaterials , 2014 , 35 ( 17 ), 4835 - 4847 . doi: 10.1016/j.biomaterials.2014.02.031 http://dx.doi.org/10.1016/j.biomaterials.2014.02.031
Yu Y. P. ; Wang Q. ; Liu Y. C. ; Xie Y. Molecular basis for the targeted binding of RGD-containing peptide to integrin αVβ3 . Biomaterials , 2014 , 35 ( 5 ), 1667 - 1675 . doi: 10.1016/j.biomaterials.2013.10.072 http://dx.doi.org/10.1016/j.biomaterials.2013.10.072
袁洋 , 蒋惠忆 , 陈伟芝 , 蒋锡群 . 长循环双靶向重组蛋白药物偶联体用于抗肿瘤治疗 . 高分子学报 , 2025 , 56 ( 2 ), 266 - 277 .
Zhang Y. ; Sun Y. C. ; Dong X. ; Wang Q. S. ; Zhu D. W. ; Mei L. ; Yan H. S. ; Lv F. A platelet intelligent vehicle with navigation for cancer photothermal-chemotherapy . ACS Nano , 2022 , 16 ( 4 ), 6359 - 6371 . doi: 10.1021/acsnano.2c00453 http://dx.doi.org/10.1021/acsnano.2c00453
Mu W. ; Chu Q. ; Liu Y. ; Zhang N. A review on nano-based drug delivery system for cancer chemoimmunotherapy . Nanomicro Lett , 2020 , 12 ( 1 ), 142 . doi: 10.1007/s40820-020-00482-6 http://dx.doi.org/10.1007/s40820-020-00482-6
Han Z. Y. ; Chen Q. W. ; Fu Z. J. ; Cheng S. X. ; Zhang X. Z. Probiotic spore-based oral drug delivery system for enhancing pancreatic cancer chemotherapy by gut-pancreas-axis-guided delivery . Nano Lett. , 2022 , 22 ( 21 ), 8608 - 8617 . doi: 10.1021/acs.nanolett.2c03131 http://dx.doi.org/10.1021/acs.nanolett.2c03131
Luo Y. F. ; Li C. ; Zhang Y. W. ; Liu P. X. ; Chen H. Y. ; Zhao Z. H. ; Wang Y. ; Zhou Z. ; Song H. L. ; Su B. Y. ; Li C. F. ; Li X. W. ; Zhang T. Y. ; You H. Y. ; Wu Y. X. ; Tian Z. H. ; Zhang S. L. ; Guo Y. ; Fan H. R. ; Chen Q. J. ; Jiang C. ; Sun T. Gradient tumor microenvironment-promoted penetrating micelles for hypoxia relief and immunosuppression reversion in pancreatic cancer treatment . Acta Biomater. , 2023 , 167 , 387 - 400 . doi: 10.1016/j.actbio.2023.05.047 http://dx.doi.org/10.1016/j.actbio.2023.05.047
Li Q. ; Dang M. ; Tao J. ; Li X. Y. ; Xiu W. J. ; Dai Z. ; He A. ; Ding M. ; Zhang Y. ; Wen Z. F. ; Su X. D. ; Elbourne A. J. ; Bao L. ; Chen L. ; Mou Y. B. ; Teng Z. G. ; Dong H. Boosting antitumor immunity via a tumor microenvironment-responsive transformable trifecta nanovaccine . Adv. Funct. Mater. , 2024 , 34 ( 26 ), 2470141 . doi: 10.1002/adfm.202470141 http://dx.doi.org/10.1002/adfm.202470141
郑西西 , 林辉 , 王利群 . 同轴电喷-去模板法制备具有金属基质蛋白酶响应性的纳米载体 . 高分子学报 , 2017 , ( 11 ), 1789 - 1795 . doi: 10.11777/j.issn1000-3304.2017.17019 http://dx.doi.org/10.11777/j.issn1000-3304.2017.17019
Guo F. Y. ; Du Y. Z. ; Wang Y. J. ; Wang M. Q. ; Wang L. Y. ; Yu N. ; Luo S. ; Wu F. ; Yang G. S. Targeted drug delivery systems for matrix metalloproteinase-responsive anoparticles in tumor cells: a review . Int. J. Biol. Macromol. , 2024 , 257 , 128658 . doi: 10.1016/j.ijbiomac.2023.128658 http://dx.doi.org/10.1016/j.ijbiomac.2023.128658
He S. J. ; Shu X. ; Wang Z. Y. ; Gao X. W. ; Feng K. ; Yang S. M. ; Shao J. Q. ; Xie N. Photofabrication of fluorescent nanospheres from de novo designed peptides, and their enzyme-responsive dissociation in living cells . Mater. Adv. , 2024 , 5 ( 7 ), 2888 - 2897 . doi: 10.1039/d4ma00024b http://dx.doi.org/10.1039/d4ma00024b
Martín C. ; Ruiz A. ; Keshavan S. ; Reina G. ; Murera D. ; Nishina Y. ; Fadeel B. ; Bianco A. A biodegradable multifunctional graphene oxide platform for targeted cancer therapy . Adv. Funct. Mater. , 2019 , 29 ( 39 ), 1901761 . doi: 10.1002/adfm.201901761 http://dx.doi.org/10.1002/adfm.201901761
Ding R. Y. ; Xu G. Q. ; Feng Y. ; Zou L. ; Chao W. Lipopeptide PAM 3 CYS 4 synergizes N -formyl-met-leu-phe (fMLP)-induced calcium transients in mouse neutrophils . Shock, 2018, 50 ( 4 ), 493 - 499 . doi: 10.1097/shk.0000000000001062 http://dx.doi.org/10.1097/shk.0000000000001062
Deng X. C. ; Liang J. L. ; Zhang S. M. ; Wang Y. Z. ; Lin Y. T. ; Meng R. ; Wang J. W. ; Feng J. ; Chen W. H. ; Zhang X. Z. Interference of ATP-adenosine axis by engineered biohybrid for amplifying immunogenic cell death-mediated antitumor immunotherapy . Adv. Mater. , 2024 , 36 ( 36 ), e 2405673 . doi: 10.1002/adma.202405673 http://dx.doi.org/10.1002/adma.202405673
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