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Charge convertible biomimetic micellar nanoparticles for enhanced melanoma-targeted therapy through tumor cells and tumor-associated macrophages dual chemotherapy with IDO immunotherapy
Luo, Kaipei1; Lian, Yunfei1; Zhang, Min1; Yu, Hua2; Wang, Guangji3; Li, Juan1
2021-05-15
Source PublicationChemical Engineering Journal
ISSN1385-8947
Volume412Pages:128659
Abstract

Immunotherapy is demonstrating great potential for cancer therapy nowadays. However, its therapeutic efficacy has been impeded by the natural biological barriers, poor immunogenicity, and highly immunosuppressive tumor microenvironment (ITM). In this study, a charge convertible biomimetic micellar nanoparticle co-encapsulated with chemotherapeutic drug paclitaxel (PTX) and indoleamine 2,3-dioxygenase (IDO) inhibitor NLG919 is developed for combined chemoimmunotherapy. The resulting nanoparticle presents prolonged blood circulation as well as specific uptake in both B16F10 melanoma cells and M2-type tumor-associated macrophages (TAM2) via folate receptor-mediated endocytosis. Moreover, rapid drug release could be elegantly triggered by the charge conversion from negative to positive in response to the acidic environment in the lysosomes. PTX can lead to immunogenic cell death to provoke antitumor immunogenicity and intratumoral infiltration of effector T cells, while the ITM is reversed by simultaneous NLG919-mediated IDO inhibition and PTX-induced TAM2 elimination. Such a biomimetic nanomedicine efficiently boosts the synergistic antitumor treatment and minimizes systemic side effects in a mouse melanoma model. Hence, this strategy demonstrates high drug delivery efficiency and provides a potential application for the combined chemoimmunotherapy of melanoma.

KeywordCharge Convertible Biomimetic Nanoparticle Combined Chemoimmunotherapy Ido Inhibition Immunogenic Cell Death M2-type Tumor-associated Macrophages
DOI10.1016/j.cej.2021.128659
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaEngineering
WOS SubjectEngineering, Environmental ; Engineering, Chemical
WOS IDWOS:000638221300002
PublisherELSEVIER SCIENCE SAPO BOX 564, 1001 LAUSANNE, SWITZERLAND
Scopus ID2-s2.0-85100431362
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Citation statistics
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
THE STATE KEY LABORATORY OF QUALITY RESEARCH IN CHINESE MEDICINE (UNIVERSITY OF MACAU)
Corresponding AuthorLi, Juan
Affiliation1.State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 210009, China
2.Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macao SAR, China
3.Center of Pharmacokinetics, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, 210009, China
Recommended Citation
GB/T 7714
Luo, Kaipei,Lian, Yunfei,Zhang, Min,et al. Charge convertible biomimetic micellar nanoparticles for enhanced melanoma-targeted therapy through tumor cells and tumor-associated macrophages dual chemotherapy with IDO immunotherapy[J]. Chemical Engineering Journal, 2021, 412, 128659.
APA Luo, Kaipei., Lian, Yunfei., Zhang, Min., Yu, Hua., Wang, Guangji., & Li, Juan (2021). Charge convertible biomimetic micellar nanoparticles for enhanced melanoma-targeted therapy through tumor cells and tumor-associated macrophages dual chemotherapy with IDO immunotherapy. Chemical Engineering Journal, 412, 128659.
MLA Luo, Kaipei,et al."Charge convertible biomimetic micellar nanoparticles for enhanced melanoma-targeted therapy through tumor cells and tumor-associated macrophages dual chemotherapy with IDO immunotherapy".Chemical Engineering Journal 412(2021):128659.
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