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Title: Enhanced cellular ablation by attenuating hypoxia status and reprogramming tumor-associated macrophages via NIR light-responsive upconversion nanocrystals
Authors: Ai, Xiangzhao
Hu, Ming
Wang, Zhimin
Lyu, Linna
Zhang, Wenmin
Li, Juan
Yang, Huanghao
Lin, Jun
Xing, Bengang
Keywords: Science::Chemistry
Issue Date: 2018
Source: Ai, X., Hu, M., Wang, Z., Lyu, L., Zhang, W., Li, J., . . . Xing, B. (2018). Enhanced cellular ablation by attenuating hypoxia status and reprogramming tumor-associated macrophages via NIR light-responsive upconversion nanocrystals. Bioconjugate Chemistry, 29(4), 928-938. doi:10.1021/acs.bioconjchem.8b00068
Journal: Bioconjugate Chemistry
Abstract: Near-infrared (NIR) light-mediated photodynamic therapy (PDT), especially based on lanthanide-doped upconversion nanocrystals (UCNs), have been extensively investigated as a promising strategy for effective cellular ablation owing to their unique optical properties to convert NIR light excitation into multiple short-wavelength emissions. Despite the deep tissue penetration of NIR light in living systems, the therapeutic efficiency is greatly restricted by insufficient oxygen supply in hypoxic tumor microenvironment. Moreover, the coexistent tumor-associated macrophages (TAMs) play critical roles in tumor recurrence during the post-PDT period. Herein, we developed a unique photosensitizer-loaded UCNs nanoconjugate (PUN) by integrating manganese dioxide (MnO2) nanosheets and hyaluronic acid (HA) biopolymer to improve NIR light-mediated PDT efficacy through attenuating hypoxia status and synergistically reprogramming TAMs populations. After the reaction with overproduced H2O2 in acidic tumor microenvironment, the MnO2 nanosheets were degraded for the production of massive oxygen to greatly enhance the oxygen-dependent PDT efficiency upon 808 nm NIR light irradiation. More importantly, the bioinspired polymer HA could effectively reprogram the polarization of pro-tumor M2-type TAMs to anti-tumor M1-type macrophages to prevent tumor relapse after PDT treatment. Such promising results provided the great opportunities to achieve enhanced cellular ablation upon NIR light-mediated PDT treatment by attenuating hypoxic tumor microenvironment, and thus facilitated the rational design of new generations of nanoplatforms toward immunotherapy to inhibit tumor recurrence during post-PDT period.
ISSN: 1043-1802
DOI: 10.1021/acs.bioconjchem.8b00068
Rights: This document is the Accepted Manuscript version of a Published Work that appeared in final form in Bioconjugate Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see
Fulltext Permission: none
Fulltext Availability: No Fulltext
Appears in Collections:SPMS Journal Articles


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