Journal Article Epublish
PubMed: 40598510 DOI: 10.1186/s12951-025-03568-8
A novel carrier-free nanoparticle with stable distinctive three-dimensional structure for tumor-targeted precision chemoimmunotherapy.
J Nanobiotechnology 23(1):480
Authors: Bo Deng, Youpeng Kong, Yingying Ma, Yijie Zhan, Yitong Sun, Rudan Wang, Pengyu Huang, Lanxia Liu
Affiliations
- State Key Laboratory of Advanced Medical Materials and Devices, Institute of Biomedical Engineering, Tianjin Institutes of Health Science, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, China.
- State Key Laboratory of Advanced Medical Materials and Devices, Institute of Biomedical Engineering, Tianjin Institutes of Health Science, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, China. School of Life Science and Biopharmaceuticals, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning, China.
- State Key Laboratory of Advanced Medical Materials and Devices, Institute of Biomedical Engineering, Tianjin Institutes of Health Science, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, China.
Abstract
Despite significant advancements in oncology, cancer remains a leading global health burden, necessitating innovative therapeutic strategies. Here, we present a novel carrier-free tumor-targeted nanomedicine system (DPA NPs) for tumor-targeted chemoimmunotherapy, formed by self-assembly of a conjugate synthesized with doxorubicin (DOX), tumor-homing peptide iRGD, matrix metalloproteinase 2 enzyme responsive peptide (MMP2), and adjuvant monophosphoryl lipid A (MPLA). The results demonstrated that DPA NPs exhibited a stable unique 3D nanostructure with tumor microenvironment (TME)-responsive properties. DPA NPs could efficiently deliver DOX to tumor cells, inducing immunogenic cell death (ICD) and simultaneously triggering tumor specific immune response. Meanwhile, MPLA amplified the anti-tumor immunity, significantly inhibiting tumor growth and metastasis. When combined with immune checkpoint inhibitors (ICIs), DPA NPs further enhanced the therapeutic outcomes in a B16 melanoma model, demonstrating remarkable suppression of tumor growth, metastasis inhibition and recurrence prevention. Mechanistic investigations across multiple biological hierarchies conclusively further confirmed the synergistic therapeutic effect. This study demonstrated that DPA NPs provide a precise, multifunctional nanoplatform for tumor-targeted combination therapy, highlighting their potential for clinical translation in cancer treatment.
MeSH
Cells, Growth, Nanoparticles, Neoplasms, Neoplasm Metastasis, Immunity, Therapeutics, Nanotechnology