Targeted reduction-responsive nanovehicles for photodynamic therapy-primed immunotherapy in melanoma

Sep 29, 2026

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Melanoma is a common, highly malignant skin tumor with persistent multidrug resistance and high recurrence, where current therapies often suffer toxicity and limited durable control. A combined photodynamic therapy (PDT) and immunotherapy approach is promising but constrained by poor photosensitizer solubility and adverse effects. This work constructs BM@HSSC nanoparticles that reduce-responsive hyaluronic acid delivers Ce6 and the PD-L1 inhibitor BMS-1 to CD44-positive tumors, enabling laser-triggered ROS generation, immunogenic cell death, dendritic cell maturation, and PD-1/PD-L1 blockade to amplify cytotoxic T-cell responses and enhance antitumor efficacy.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Introduction

Background and clinical challenges

Design concept and nanoparticle mechanism

BM@HSSC composition and tumor targeting

Ce6/PDT and ICD induction

BMS-1 immune checkpoint blockade

Journal of Pharmaceutical Analysis 15 (2025) 101311 Contents lists available at ScienceDirect Journal of Pharmaceutical Analysis journal [homepage:](homepage: www. elsevier. com/locate/jpa)[ www. elsevier. com/locate/jpa](homepage: www. elsevier. com/locate/jpa) | Original article | | | | | --- | --- | --- | --- | | Targeted reduction-responsive nanovehicles for photodynamic therapy-primed immunotherapy in melanoma | | | | | Chenqian Feng a, 1, Lingfeng Zhou a, 1, Bo Chen a, Hui Li a, Min Mu a, Rangrang Fan b, Haifeng Chen b, **, Gang Guo a, *
a State Key Laboratory of Biotherapy and Cancer Center, Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, 610041, China b Department of Neurosurgery and Institute of Neurosurgery, West China Hospital, Sichuan University, Chengdu, 610041, China | | | | | a r t i c l e i n f o | | a b s t r a c t | | | Article history:
Received 28 November 2024
Received in revised form
5 April 2025
Accepted 10 April 2025
Available online 11 April 2025 | | Melanoma, a common malignant skin tumor, faces challenges with multidrug resistance and high recurrence rates. Combining photodynamic therapy (PDT) and immunotherapy offers a promising personalized treatment approach. However, poor water solubility and signiﬁcant side effects of photosensitizers and immune checkpoint inhibitors (ICIs) limit their application. Enhancing delivery efﬁciency while reducing adverse effects is crucial. Herein, we formulate BM@HSSC nanoparticles (NPs), which consist of a reduction-responsive hyaluronic acid (HA) backbone modiﬁed with photosensitizer chlorine6 (Ce6) and loaded with the programmed cell death-ligand 1 (PD-L1) inhibitor BMS-1. This system synergistically integrates PDT, immunogenic cell death (ICD), and immunotherapy for melanoma treatment. BM@HSSC NPs target and accumulate at the tumor site via the CD44 receptor. The disulﬁde bonds (-S-S-) in the NPs react with high glutathione (GSH) concentrations in tumor cells, rapidly releasing Ce6 and BMS-1. Under 660 nm laser irradiation, BM@HSSC NPs generate cytotoxic reactive oxygen species (ROS), inducing cell apoptosis and triggering ICD via PDT damage-associated molecular patterns (DAMPs) and tumor-associated antigens (TAAs) released from ICD promote dendritic cell (DC) maturation, enhancing antigen presentation and activating cytotoxic T lymphocytes (CTLs). Meanwhile, BMS-1 blocks the programmed cell death-1 (PD-1)/PD-L1 pathway, countering the immunosuppressive tumor microenvironment (iTME) and inhibiting tumor cell immune escape. This strategy ampliﬁes antitumor immune responses by enhancing immunogenicity and synergizing with ICIs, resulting in robust antitumor efﬁcacy.
© 2025 The Authors. Published by Elsevier B.V. on behalf of Xi’an Jiaotong University. This is an open access article under the CC BY-NC-ND license ([http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/)). | | | Keywords:
Hyaluronic acid Immunogenic cell death Photodynamic therapy Immune checkpoint blockade Reduction responsive | | | | 1. Introduction Melanoma, recognized as one of the most aggressive malignant skin tumors, poses a signiﬁcant threat to patient health and survival [1]. Characterized by poor prognosis and high mortality rates, patients often succumb within months of diagnosis [2]. Traditional melanoma treatment strategies, including clinical surgery, chemotherapy, and radiotherapy, have shown some clinical efﬁcacy [3]. However, these methods are limited by high toxicity, multidrug resistance, and a propensity for recurrence [4,5]. Consequently, recent research in melanoma therapy has shifted from Peer review under responsibility of Xi'an Jiaotong University. * Corresponding author. ** Corresponding author. E-mail addresses: [chfbox@wchscu.cn](chfbox@wchscu.cn) (H. Chen), [guogang@scu.edu.cn](guogang@scu.edu.cn) (G. Guo). 1 Both authors contributed equal

FAQs

What therapeutic actions drive the synergistic antitumor effect?

Under 660 nm laser irradiation, the system generates cytotoxic ROS to induce apoptosis and immunogenic cell death, while BMS-1 blocks the PD-1/PD-L1 pathway to counter immunosuppression and prevent immune escape.

Sep 29, 2026

Uploaded by Đào