A novel carrier-free nanoparticle with stable distinctive three-dimensional structure for tumor-targeted precision chemoimmunotherapy

Sep 24, 2026

Despite significant advancements in oncology, cancer remains a leading global health burden, necessitating innovative therapeutic strategies. This study presents a novel carrier-free tumor-targeted nanomedicine system (DPA NPs) built by self-assembly of a conjugate incorporating doxorubicin, iRGD, an MMP2-responsive peptide, and MPLA. DPA NPs form a stable 3D nanostructure with tumor microenvironment responsiveness, enabling efficient DOX delivery, immunogenic cell death, and tumor-specific immune activation.

LanguageEnglish

CategoryHealthcare

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Pages15

Reading Time38 min

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Abstract

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Introduction

Deng et al. Journal of Nanobiotechnology (2025) 23:480 [https://doi.org/10.1186/s12951-025-03568-8](https://doi.org/10.1186/s12951-025-03568-8) Journal of Nanobiotechnology RESEARCH Open Access A novel carrier-free nanoparticle with stable distinctive three-dimensional structure for tumor-targeted precision chemoimmunotherapy Bo Deng1†, Youpeng Kong1†, Yingying Ma1, Yijie Zhan1, Yitong Sun1,2, Rudan Wang1,2, Pengyu Huang1 and Lanxia Liu 1* 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 tumortargeted combination therapy, highlighting their potential for clinical translation in cancer treatment. Highlights • Self-assembled, three-dimensional, carrier-free nanoparticles integrate DOX, iRGD, MMP2-responsive peptide, and MPLA to enable TME-responsive therapy. • Dual cell targeting facilitates precise delivery of DOX to tumor cells and MPLA to dendritic cells, enhancing therapeutic accuracy and safety. • Robust ICD-driven immune responses synergistically eradicate tumors, inhibit metastasis, and prevent recurrence. Keywords Combination therapy, Nanovaccine, Immunogenic cell death, Immunotherapy †Bo Deng andYoupeng Kong contributed equally to this work. *Correspondence: Lanxia Liu [liulanxiabme@163.com](liulanxiabme@163.com) Full list of author information is available at the end of the article © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/.)[.](http://creativecommons.org/licenses/by-nc-nd/4.0/.) Deng et al. Journal of Nanobiotechnology (2025) 23:480 Page 2 of 15 Graphical Abstract Introduction Cancer remains a formidable global health challenge, with high morbidity and mortality rates despite signi

FAQs

What is the main therapeutic concept behind DPA NPs?

DPA NPs are a carrier-free, tumor-targeted nanomedicine system designed for combined chemoimmunotherapy, delivering doxorubicin while simultaneously triggering immune responses through immunogenic cell death and MPLA-mediated immune activation.

How do DPA NPs achieve tumor microenvironment responsiveness?

They rely on a stable, distinctive three-dimensional structure that includes an MMP2-responsive peptide component, enabling responsiveness to the tumor microenvironment for targeted activity.

What is the benefit of combining DPA NPs with immune checkpoint inhibitors?

In a B16 melanoma model, combining DPA NPs with immune checkpoint inhibitors further enhances therapeutic outcomes, producing stronger suppression of tumor growth, metastasis inhibition, and recurrence prevention.

Sep 24, 2026

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