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MnCaCs-Biomineralized Oncolytic Virus for Bimodal Imaging-Guided and Synergistically Enhanced Anticancer Therapy
Li-Li Huang1, Xue Li1, JinFeng Zhang1
1School of Life Science , Beijing Institute of Technology , Beijing 100081 , People's Republic of China.
Abstract:
Oncolytic adenovirus (OA) is an ideal candidate for clinical anticancer treatment, because it can specifically replicate in tumor cells with high titer. However, its systemic administration is still hindered, because of severely compromised antitumor efficacy. Herein, an engineered OA was innovatively developed by enwrapping OA with calcium and manganese carbonates (MnCaCs) biomineral shell, which could protect the virus from removal of the host immune system and prolong its in vivo circulation. Upon accumulating in tumor sites, MnCaCs readily dissolved under the acidic microenvironment, releasing Mn2+ that could convert endogenous H2O2 into oxygen (O2) and then enhance the duplication ability of OA, thus significantly increased the antitumor efficacy. Meanwhile, Mn2+ and the increased O2 individually endowed the T1 modal magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) feasibility, providing real-time monitoring information for the therapy. This versatile engineered OA demonstrated its promise for visible and efficient oncolytic virotherapy by systemic administration.
Insights
Engineered oncolytic adenoviruses (OA) wrapped in biomineral shells show enhanced antitumor efficacy and circulation time. This novel approach improves cancer virotherapy through targeted drug delivery and real-time imaging.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Oncolytic adenoviruses (OA) show promise for cancer treatment due to tumor-specific replication.
- Systemic administration of OA is limited by reduced antitumor efficacy and immune system clearance.
Purpose of the Study:
- To develop an engineered OA with enhanced systemic delivery and antitumor efficacy.
- To utilize a biomineral shell for viral protection and tumor microenvironment-responsive drug release.
- To enable real-time monitoring of therapy using advanced imaging techniques.
Main Methods:
- Engineered OA by enwrapping with calcium and manganese carbonates (MnCaCs) biomineral shell.
- Investigated MnCaCs' protective effect on OA during systemic circulation.
- Assessed Mn2+-mediated oxygen generation in acidic tumor microenvironments to enhance OA replication.
- Evaluated T1-modal magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) for therapy monitoring.
Main Results:
- MnCaCs shell protected OA from immune clearance and prolonged in vivo circulation.
- Acidic tumor microenvironment triggered MnCaCs dissolution, releasing Mn2+.
- Released Mn2+ converted H2O2 to O2, enhancing OA replication and antitumor efficacy.
- Achieved visible and real-time monitoring of OA therapy using MRI and PAI.
Conclusions:
- Engineered OA with MnCaCs biomineral shell offers a promising strategy for effective systemic oncolytic virotherapy.
- The developed system enhances viral delivery, tumor cell killing, and provides theranostic capabilities.
- This versatile platform demonstrates significant potential for visible and efficient anticancer treatment.
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