期刊
NATURE MATERIALS
卷 20, 期 10, 页码 1440-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41563-021-01042-y
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资金
- Koch Institute Support Grant from the National Cancer Institute (Swanson Biotechnology Center) [P30-CA14051]
- National Institute of Environmental Health Sciences [P30-ES002109]
- Koch Institute Frontier Research Program via the Casey and Family Foundation Cancer Research Fund
- Virginia and D.K. Ludwig Fund for Cancer Research
- KI Quinquennial Cancer Research Fellowship
- American Cancer Society
- Ludwig Center for Molecular Oncology at MIT
- Koch Institute Marble Center for Cancer Nanomedicine
Multimodal nanosensors have been developed to target and respond to hallmarks in the tumor microenvironment and provide both a non-invasive urinary monitoring tool and an on-demand positron emission tomography imaging agent to localize tumor metastasis and assess response to therapy. Through tailored target specificities, this modular platform has the capacity to be engineered as a pan-cancer test that may guide treatment decisions for numerous tumor types.
Therapeutic outcomes in oncology may be aided by precision diagnostics that offer early detection, localization and the opportunity to monitor response to therapy. Here, we report a multimodal nanosensor engineered to target tumours through acidosis, respond to proteases in the microenvironment to release urinary reporters and (optionally) carry positron emission tomography probes to enable localization of primary and metastatic cancers in mouse models of colorectal cancer. We present a paradigm wherein this multimodal sensor can be employed longitudinally to assess burden of disease non-invasively, including tumour progression and response to chemotherapy. Specifically, we showed that acidosis-mediated tumour insertion enhanced on-target release of matrix metalloproteinase-responsive reporters in urine. Subsequent on-demand loading of the radiotracer Cu-64 allowed pH-dependent tumour visualization, enabling enriched microenvironmental characterization when compared with the conventional metabolic tracer F-18-fluorodeoxyglucose. Through tailored target specificities, this modular platform has the capacity to be engineered as a pan-cancer test that may guide treatment decisions for numerous tumour types. Multimodal nanosensors have been developed to target and respond to hallmarks in the tumour microenvironment and provide both a non-invasive urinary monitoring tool and an on-demand positron emission tomography imaging agent to localize tumour metastasis and assess response to therapy.
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