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Vol. 19 (2027)

A Manganese-Chlorella Hydrogel for an Integrated “Remove–Remodel–Repair” Strategy in Pancreatic Cancer Therapy

https://doi.org/10.1007/s40820-026-02344-z
Tinglin Zhang
Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, People’s Republic of China
Zhu Peng
Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, People’s Republic of China
Shijin Zhao
Department of Gastroenterology, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, People’s Republic of China
Xin Jin
Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China
Yiqi Du
Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, People’s Republic of China
Zhaoshen Li
Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, People’s Republic of China
Kaixuan Wang
Department of Gastroenterology, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, People’s Republic of China
Jie Gao
Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, People’s Republic of China

Corresponding Author: Jie Gao

gaojiehighclea@smmu.edu.cn

Nano-Micro Letters, Vol. 19 (2027), Article Number: 45

Abstract

Pancreatic cancer faces the challenges of tumor progression and postoperative pancreatic fistula during the perioperative period, which severely affect patient prognosis. In this study, an injectable self-healing multifunctional hydrogel (CMCGel) was developed based on dynamic cross‑linking between manganese ions (Mn2+) and carboxymethyl chitosan loaded with chlorella extract (CE). This platform implements an integrated “Remove–Remodel–Repair” (3R) strategy for comprehensive perioperative management. CMCGel exhibits distinctive pH/laser dual-responsive behavior: In the acidic tumor microenvironment, the accelerated release of CE and Mn2+ enhances photodynamic therapy and chemodynamic therapy (CDT). This combination, activated by laser and gated by endogenous pH, achieves remarkable tumor suppression rates of 85.81% in vitro and 96.01% in vivo. As pH normalizes, Mn2+ shifts from CDT to activate the cyclic GMP-AMP synthase stimulator of interferon genes (cGAS-STING) pathway, remodeling the immune microenvironment. Crucially, CMCGel’s adhesion strength in artificial pancreatic fluid at 48 h was 4703.80 ± 50.36 Pa, only 8.17% lower than that at 10 min. This enzyme-resistant property enables durable mechanical sealing at the fistula site, reducing amylase leakage by 55.71% and creating favorable conditions for tissue repair. By integrating pH/laser-triggered combination therapy, immunomodulation, and enzyme-resistant barrier functionality into a single platform, CMCGel presents a clinically promising strategy for perioperative management of pancreatic cancer.


Highlights:
1 An injectable, self-healing hydrogel (CMCGel) is engineered via dynamic cross-linking of manganese ions and carboxymethyl chitosan to load chlorella extract.
2 The pH/laser dual-responsive platform with endogenous pH gating and exogenous laser switching enables a programmed “Remove–Remodel–Repair” (3R) strategy.
3 CMCGel achieves remarkable tumor suppression (96.01% in vivo), effectively remodels the antitumor immune microenvironment, and promotes postoperative pancreatic fistula repair through durable sealing and anti-inflammatory effects.

Keywords

Pancreatic cancer Pancreatic fistula Integrative therapy Hydrogels Photodynamic therapy cGAS-STING pathway Immunotherapy
Zhang, Tinglin, Zhu Peng, Shijin Zhao, Xin Jin, Yiqi Du, Zhaoshen Li, Kaixuan Wang, and Jie Gao. 2026. “A Manganese-Chlorella Hydrogel for an Integrated ‘Remove–Remodel–Repair’ Strategy in Pancreatic Cancer Therapy”. Nano-Micro Letters 19 (September):45. https://doi.org/10.1007/s40820-026-02344-z.
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