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Biomineralized outer membrane vesicles for synergistic immuno-photodynamic therapy of oral squamous cell carcinoma
Jingyuan Wang1,2, Guanxiong Zhu1,2, Hongru Zhang1,2
1Department of Preventive Dentistry, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Medical University, Guangzhou, Guangdong 510182, PR China.
Abstract:
Immunotherapy against oral squamous cell carcinoma (OSCC) currently exhibits a clinical response rate significantly lower than anticipated, underscoring the need for more effective therapeutic strategies. Outer membrane vesicles (OMVs) represent promising natural immune modulators; however, their systemic application is limited by risks such as cytokine storms and inadequate tumor accumulation. To overcome these challenges, this study developed biomineralized OMVs coated with calcium phosphate (CaP) and subsequently loaded with the photosensitizer chlorin e6 (Ce6) on the surface, termed OMVs@CaP-Ce6 (OCC). The resulting OCC demonstrates enhanced tumor accumulation and responsiveness to acidic conditions, including the tumor microenvironment (TME). Under acidic pH conditions, the CaP shell disintegrates, releasing both OMVs and Ce6 to enable synergistic immunotherapy and photodynamic therapy (PDT). PDT promotes cancer cell apoptosis, while OMVs activate antitumor immunity by modulating immune responses. Studies demonstrate that OCC, as a highly biocompatible and synergistic platform, effectively suppresses tumor growth under laser irradiation by eliminating cancer cells and reversing the immunosuppressive TME to enhance antitumor immunity. This spatiotemporal and biomineralized OCC system maximizes the immunotherapeutic potential of OMVs, overcomes the limitations of conventional monotherapies, and offers a promising alternative strategy for the effective treatment of OSCC.
Insights
This study introduces biomineralized outer membrane vesicles (OMVs) loaded with chlorin e6 (Ce6) for oral squamous cell carcinoma (OSCC) treatment. This novel platform combines photodynamic therapy (PDT) and immunotherapy for enhanced antitumor immunity.
Area of Science:
- Oncology
- Immunology
- Biomaterials Science
Background:
- Current immunotherapy for oral squamous cell carcinoma (OSCC) has limited clinical response rates.
- Outer membrane vesicles (OMVs) show promise as immune modulators but face challenges in systemic application due to toxicity and poor tumor accumulation.
- Developing advanced therapeutic strategies is crucial for improving OSCC treatment outcomes.
Purpose of the Study:
- To develop a novel therapeutic platform, OMVs@CaP-Ce6 (OCC), for synergistic immunotherapy and photodynamic therapy (PDT) against OSCC.
- To enhance tumor accumulation and responsiveness to the acidic tumor microenvironment (TME) using biomineralized OMVs.
- To overcome the limitations of conventional monotherapies and improve the efficacy of OSCC treatment.
Main Methods:
- Biomineralization of OMVs using calcium phosphate (CaP) coating.
- Surface loading of the photosensitizer chlorin e6 (Ce6) onto CaP-coated OMVs, creating the OCC system.
- Evaluation of OCC's tumor accumulation, pH responsiveness, and synergistic therapeutic effects in vitro and in vivo.
Main Results:
- The developed OCC system demonstrated enhanced tumor accumulation and triggered drug release in acidic TME conditions.
- Synergistic effects of PDT (inducing cancer cell apoptosis) and immunotherapy (activating antitumor immunity) were observed.
- OCC effectively suppressed tumor growth under laser irradiation by eliminating cancer cells and reversing the immunosuppressive TME.
Conclusions:
- The biomineralized OCC system offers a biocompatible and synergistic platform for effective OSCC treatment.
- This approach maximizes the immunotherapeutic potential of OMVs and overcomes limitations of monotherapies.
- OCC presents a promising alternative strategy for enhancing antitumor immunity and treating OS squamous cell carcinoma.
