Journal
ACS NANO
Volume 13, Issue 3, Pages 3083-3094Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.8b08346
Keywords
immunogenetic cell death; photodynamic therapy; polymersomes as adjuvant; in situ DC vaccine; colorectal cancer immunotherapy
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Funding
- Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH)
- National Natural Science Foundation of China [NSFC 81471689, 81771873, 91859207]
- NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING [ZICEB000087] Funding Source: NIH RePORTER
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A cancer vaccine is an important form of immunotherapy. Given their effectiveness for antigen processing and presentation, dendritic cells (DCs) have been exploited in the development of a therapeutic vaccine. Herein, a versatile polymersomal nanoformulation that enables generation of tumor-associated antigens (TAAs) and simultaneously serves as adjuvant for an in situ DC vaccine is reported. The chimeric cross-linked polymersome (CCPS) is acquired from self-assembly of a triblock copolymer, polyethylene glycol-poly(methyl methyacrylate-co-2-amino ethyl methacrylate (thiol/amine))-poly 2-(dimethylamino) ethyl methacrylate (PEG-P(M.MA-co-AEMA (SH/NH2)-PDMA). CCPS can encapsulate low dose doxorubicin hydrochloride (DOX) to induce immunogenic cell death (ICD) and 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH), a photosensitizer to facilitate photodynamic therapy (PDT) for reactive oxygen species (ROS) generation. This combination is able to enhance the population of TAAs and DC recruitment, eliciting an immune response cascade. In addition, CCPS with primary and tertiary amines act as adjuvant, both of which can stimulate DCs recruited to form an in situ DC vaccine after combination with TAAs for MC38 colorectal cancer treatment. In vivo results indicate that the all-in-one polymersomal nanoformulation (CCPS/HPPH/DOX) increases mature DCs in tumor-draining lymph nodes (tdLNs) and CD8(+) T cells in tumor tissues to inhibit primary and distant MC38 tumor growth following a single intravenous injection with a low dose of DOX and HPPH.
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