DB-PTZ: A Novel NIR-II AIE Photosensitizer for Image-Guided Photothermal and Photodynamic Therapy of Hepatocellular Carcinoma

  • ACS Appl Mater Interfaces. 2026 Apr 15;18(14):20175-20188. doi: 10.1021/acsami.6c01570.
Qingqing Wu  1  2 ,  Yumeng Liu  1 ,  Lu Zhou  1 ,  Weiyi Zhao  1 ,  Miaoyu Wei  1 ,  Yueqin Zhang  1 ,  Shuanglin Han  3 ,  Muhammad Umar  4 ,  Mu He  1  2 ,  Jun Tong  1  2 ,  Ting Zhou  1  2 ,  Zehao Yao  1  2 ,  Lidong Cao  1 ,  Chengwu Zhang  1 ,  Changwei Dou  1
Affiliations
  • 1. General Surgery, Cancer Center, Department of Hepatobiliary & Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China.
  • 2. Graduate School of Hangzhou Normal University, Hangzhou 311121, Zhejiang Province, China.
  • 3. Department of Gastroenterology, The Second Hospital of Dalian Medical University, No.467, Zhongshan Road, Shahekou District, Dalian 116000, Liaoning Province, China.
  • 4. International Education College of Zhejiang Chinese Medical University, Hangzhou 310014, Zhejiang Province, China.
PMID: 41941216 DOI: 10.1021/acsami.6c01570
Abstract

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, and treatment options for advanced disease are still inadequate. Photodynamic therapy (PDT) offers a minimally invasive alternative by generating cytotoxic reactive oxygen species (ROS) upon Photosensitizer activation, yet its efficacy is limited by the hypoxic tumor microenvironment. We developed a novel near-infrared II (NIR-II) aggregation-induced emission (AIE) Photosensitizer, DB-PTZ, by combining the electron donor phenothiazine with the electron acceptor malononitrile and introducing conjugated peripheral groups to enhance electron delocalization. DB-PTZ nanoparticles, prepared via 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy (polyethylene glycol)-2000 (DSPE-PEG2000) encapsulation, exhibited uniform size (∼45 nm), negative surface charge (∼35.82 mV), high photothermal conversion efficiency (∼49%), robust stability, minimal hemolysis (<4% at 25 μg/mL), and efficient, time-dependent cellular uptake with lysosomal escape. Under 808 nm laser irradiation (0.8 W·cm-2), DB-PTZ significantly increased intracellular ROS, induced Apoptosis (44.74%), and inhibited the proliferation, migration, and invasion of HCC cells. In vivo, DB-PTZ selectively accumulated in Tumors, providing potent growth suppression without measurable systemic toxicity. These results establish DB-PTZ as a hypoxia-tolerant NIR-II AIE Photosensitizer with dual photothermal-photodynamic activity, offering a promising platform for precise, image-guided theranostics in HCC.

Keywords
DB-PTZ; apoptosis; diagnosis; hepatocellular carcinoma; photodynamic therapy; treatment strategy.
Products