Nanoconjugates to enhance PDT-mediated cancer immunotherapy by targeting the indoleamine-2,3-dioxygenase pathway

• Type of Material: Article
• Authors: Xueyuan Yang, University of Georgia; Weizhong Zhang, University of Georgia; Wen Jiang, University of Georgia; Anil Kumar, University of Georgia; Shiyi Zhou, University of Georgia; Zhengwei Cao, University of Georgia; Shuyue Zhan, University of Georgia; Wei Yang, University of Georgia; Rui Liu, University of Georgia; Yong Teng, Emory University; Jin Xie, University of Georgia
• Language: English
• Date: 2021-06-14
• Publisher: BMC
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2021
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s12951-021-00919-z
• Title of Journal or Parent Work: JOURNAL OF NANOBIOTECHNOLOGY
• Volume: 19
• Issue: 1
• Start Page: 182
• End Page: 182
• Grant/Funding Information: This work was supported by the National Science Foundation (CAREER Grant no. NSF1552617 to J.X.), the National Institute of Biomedical Imaging and Bioengineering (Grant no. R01EB022596 to J.X.), the National Cancer Institute (Grant no. R01CA247769 and R01CA257851 to J.X.), and the National Institute of Dental and Craniofacial Research (R01DE028351 to Y. T.).
• Keywords: Nanoscience & Nanotechnology; IMMUNE ESCAPE; Life Sciences & Biomedicine; Science & Technology; INHIBITION; Science & Technology - Other Topics; Cancer; PHOTODYNAMIC-THERAPY; Immunotherapy; IDO; Photodynamic therapy; INDOLEAMINE 2,3-DIOXYGENASE; Nanoparticles; Biotechnology & Applied Microbiology; DENDRITIC CELLS; Ferritin; RESISTANCE
• Research Categories: Health Sciences, Oncology; Chemistry, General

Abstract

Background: Photodynamic therapy (PDT) may elicit antitumor immune response in addition to killing cancer cells. However, PDT as a monotherapy often fails to induce a strong immunity. Immune checkpoint inhibitors, which selectively block regulatory axes, may be used in combination with PDT to improve treatment outcomes. Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme and an important meditator of tumor immune escape. Combination therapy with PDT and IDO-targeted immune checkpoint blockage is promising but has been seldom been explored. Methods: Herein we report a composite nanoparticle that allows for simultaneous delivery of photosensitizer and IDO inhibitor. Briefly, we separately load ZnF16Pc, a photosensitizer, and NLG919, an indoleamine 2,3-dioxygenase (IDO) inhibitor, into ferritin and poly(lactide-co-glycolic)-block-poly(ethylene glycol) (PEG-PLGA) nanoparticles; we then conjugate these two compartments to form a composite nanoparticle referred to as PPF NPs. We tested combination treatment with PPF NPs first in vitro and then in vivo in B16F10-tumor bearing C57/BL6 mice. Results: Our results showed that PPF NPs can efficiently encapsulate both ZnF16Pc and NLG919. In vivo studies found that the combination treatment led to significantly improved tumor suppression and animal survival. Moreover, the treatment increased tumor infiltration of CD8+ T cells, while reducing frequencies of MDSCs and Tregs. 30% of the animals showed complete tumor eradication, and they successfully rejected a second tumor inoculation. Overall, our studies introduce a unique composite nanoplatform that allows for co-delivery of photosensitizer and IDO inhibitor with minimal inter-species interference, which is ideal for combination therapy. [Figure not available: see fulltext.].