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Inducing enhanced immunogenic cell death with nanocarrier-based drug delivery systems for pancreatic cancer therapy

Paper ID Volume ID Publish Year Pages File Format Full-Text
5320 366 2016 11 PDF Available
Title
Inducing enhanced immunogenic cell death with nanocarrier-based drug delivery systems for pancreatic cancer therapy
Abstract

Immunogenic cell death (ICD) occurs when apoptotic tumor cell elicits a specific immune response, which may trigger an anti-tumor effect, via the release of immunostimulatory damage-associated molecular patterns (DAMPs). Hypothesizing that nanomedicines may impact ICD due to their proven advantages in delivery of chemotherapeutics, we encapsulated oxaliplatin (OXA) or gemcitabine (GEM), an ICD and a non-ICD inducer respectively, into the amphiphilic diblock copolymer nanoparticles. Neither GEM nor nanoparticle-encapsulated GEM (NP-GEM) induced ICD, while both OXA and nanoparticle-encapsulated OXA (NP-OXA) induced ICD. Interestingly, NP-OXA treated tumor cells released more DAMPs and induced stronger immune responses of dendritic cells and T lymphocytes than OXA treatment in vitro. Furthermore, OXA and NP-OXA exhibited stronger therapeutic effects in immunocompetent mice than in immunodeficient mice, and the enhancement of therapeutic efficacy was significantly higher in the NP-OXA group than the OXA group. Moreover, NP-OXA treatment induced a higher proportion of tumor infiltrating activated cytotoxic T-lymphocytes than OXA treatment. This general trend of enhanced ICD by nanoparticle delivery was corroborated in evaluating another pair of ICD inducer and non-ICD inducer, doxorubicin and 5-fluorouracil. In conclusion, although nanoparticle encapsulation did not endow a non-ICD inducer with ICD-mediated anti-tumor capacity, treatment with a nanoparticle-encapsulated ICD inducer led to significantly enhanced ICD and consequently improved anti-tumor effects than the free ICD inducer. The proposed nanomedicine approach may impact cancer immunotherapy via the novel cell death mechanism of ICD.

Keywords
Nanocarriers; Immunogenic cell death; Dendritic cells; Oxaliplatin; Gemcitabine; Pancreatic cancer
First Page Preview
Inducing enhanced immunogenic cell death with nanocarrier-based drug delivery systems for pancreatic cancer therapy
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 102, September 2016, Pages 187–197
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering