Related Experiment Video
Updated: Sep 6, 2025
Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles
Published on: December 1, 2016
Siglec15 Checkpoint Blockade for Simultaneous Immunochemotherapy and Osteolysis Inhibition in Lung Adenocarcinoma
Haifeng Liang1,2, Lei Zhou1,2, Zhichao Hu1,2
1Department of Orthopaedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Abstract:
Low responsiveness to anti-programmed death-1/programmed death-ligand 1 (anti-PD-1/PD-L1) for solid tumors indicates the presence of other immunosuppressive pathways. Siglec15, a newly discovered immune checkpoint, has been reported to repress immune responses in the tumor microenvironment (TME) and regulate osteoclast differentiation. However, the role of Siglec15 in the treatment for bone metastasis remains unclear. Herein, Siglec15 shows significantly higher expression in lung adenocarcinoma spinal metastasis (LUAD-SM) than in para-cancerous spinal tissues and primary LUAD. Subsequently, a TME-responsive hollow MnO2 nanoplatform (H-M) loaded with Siglec15 siRNA and cisplatin (H-M@siS15/Cis) is developed, and the surface is modified with an aspartic acid octapeptide (Asp8 ), thus allowing H-M to target spinal metastasis. High drug-loading capacity, good biocompatibility, effective tumor accumulation, and efficient Siglec15 silencing are demonstrated. Furthermore, the nanoparticles could reverse immunosuppression caused by tumor cells and tumor-associated macrophages (TAMs) and inhibit osteoclast differentiation via Siglec15 downregulation in vitro. In a LUAD-SM mouse model, H-M@siS15/Cis-Asp8 exhibits superior therapeutic efficacy via synergetic immunochemotherapy and osteolysis inhibition. Taken together, this single nanoplatform reveals the therapeutic potential of the new immune checkpoint Siglec15 in LUAD-SM and provides a strategy to treat this disease.
Insights
This study introduces a novel nanoplatform targeting Siglec-15, a new immune checkpoint, to treat lung adenocarcinoma with bone metastasis. The therapy combines chemotherapy and immune suppression reversal for enhanced efficacy.
Area of Science:
- Oncology
- Immunology
- Nanomedicine
Background:
- Low response to anti-PD-1/PD-L1 therapies suggests alternative immunosuppressive pathways in solid tumors.
- Siglec-15, a novel immune checkpoint, suppresses immune responses and influences osteoclast differentiation, but its role in bone metastasis is unknown.
Purpose of the Study:
- To investigate the role of Siglec-15 in lung adenocarcinoma spinal metastasis (LUAD-SM).
- To develop a targeted nanoplatform for synergistic chemo-immunotherapy and osteolysis inhibition in LUAD-SM.
Main Methods:
- Siglec-15 expression analysis in LUAD-SM tissues.
- Development of a TME-responsive hollow MnO2 nanoplatform (H-M) loaded with Siglec-15 siRNA and cisplatin, surface-modified with Asp8 for spinal metastasis targeting.
- In vitro assessment of nanoplatform biocompatibility, drug loading, Siglec-15 silencing, and immunomodulatory effects.
- In vivo evaluation of therapeutic efficacy in a LUAD-SM mouse model.
Main Results:
- Siglec-15 is significantly upregulated in LUAD-SM compared to normal tissues.
- The developed nanoplatform (H-M@siS15/Cis-Asp8) demonstrated high drug loading, biocompatibility, tumor targeting, and efficient Siglec-15 silencing.
- In vitro studies showed reversal of immunosuppression and inhibition of osteoclast differentiation.
- The nanoplatform achieved superior therapeutic outcomes in vivo through combined chemo-immunotherapy and osteolysis inhibition.
Conclusions:
- Siglec-15 plays a crucial role in LUAD-SM and represents a potential therapeutic target.
- The developed nanoplatform offers a promising strategy for treating LUAD-SM by combining immunotherapy and chemotherapy while inhibiting bone destruction.
More Related Videos
08:47Improved Visualization of Lung Metastases at Single Cell Resolution in Mice by Combined In-situ Perfusion of Lung Tissue and X-Gal Staining of lacZ-Tagged Tumor Cells
Published on: August 21, 2012
07:24Repression of Multiple Myeloma Cell Growth In Vivo by Single-wall Carbon Nanotube SWCNT-delivered MALAT1 Antisense Oligos
Published on: December 13, 2018
