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Supplementary Materials from Chemotherapy-Induced Macrophage Infiltration into Tumors Enhances Nanographene-Based Photodynamic Therapy

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posted on 2023-03-31, 01:45 authored by Yang Zhao, Chenran Zhang, Liquan Gao, Xinhe Yu, Jianhao Lai, Dehua Lu, Rui Bao, Yanpu Wang, Bing Jia, Fan Wang, Zhaofei Liu

The Supplementary Materials file contains the following: 1) Supplementary Methods; 2) Supplementary Fig. S1: structure and characterizations of GO(HPPH)-PEG; 3) Supplementary Fig. S2: in vitro stability of GO(HPPH)-PEG; 4) Supplementary Fig. S3: singlet oxygen sensor green assay for free HPPH and GO(HPPH)-PEG; 5) Supplementary Fig. S4: in vivo NIRF imaging of free HPPH and GO(HPPH)-PEG; 6) Supplementary Fig. S5: in vivo PDT efficiency of free HPPH and GO(HPPH)-PEG; 7) Supplementary Fig. S6: in vivo NIRF imaging of 4T1 tumor-bearing mice after intratumoral injection of IRDye800-labeled F4/80+ macrophages; 8) Supplementary Fig. S7: ex vivo microdistribution analysis of CM-DiI-labeled F4/80+ macrophages in tumor tissues; 9) Supplementary Fig. S8: ex vivo NIRF imaging of GO(HPPH)-PEG; 10) Supplementary Fig. S9: flow cytometric analysis of integrin β6 for 4T1 tumor cells; 11) Supplementary Fig. S10: in vivo NIRF imaging of GO(HPPH)-PEG in control and CTX-treated 4T1 tumor-bearing mice; 12) Supplementary Fig. S11: immunofluorescence analysis of integrin β6 and F4/80 in 4T1 tumor tissues; 13) Supplementary Fig. S12: the synthetic scheme of IRDye800-αF4/80-Fab and 99mTc-αF4/80-Fab; 14) Supplementary Fig. S13: SDS-PAGE and in vitro NIRF imaging of IRDye800-αF4/80-Fab and αF4/80-Fab; 15) Supplementary Fig. S14: in vitro macrophage-specific binding of IRDye800-αF4/80-Fab; 16) Supplementary Fig. S15: in vivo specific targeting of IRDye800-αF4/80-Fab; 17) Supplementary Fig. S16: in vitro macrophage-specific binding of 99mTc-αF4/80-Fab.

Funding

National Basic Research Program

National Natural Science Foundation of China

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ARTICLE ABSTRACT

Increased recruitment of tumor-associated macrophages (TAM) to tumors following chemotherapy promotes tumor resistance and recurrence and correlates with poor prognosis. TAM depletion suppresses tumor growth, but is not highly effective due to the effects of tumorigenic mediators from other stromal sources. Here, we report that adoptive macrophage transfer led to a dramatically enhanced photodynamic therapy (PDT) effect of 2-(1-hexyloxyethyl)-2-devinyl pyropheophor-bide-alpha (HPPH)-coated polyethylene glycosylated nanographene oxide [GO(HPPH)-PEG] by increasing its tumor accumulation. Moreover, tumor treatment with commonly used chemotherapeutic drugs induced an increase in macrophage infiltration into tumors, which also enhanced tumor uptake and the PDT effects of GO(HPPH)-PEG, resulting in tumor eradication. Macrophage recruitment to tumors after chemotherapy was visualized noninvasively by near-infrared fluorescence and single-photon emission CT imaging using F4/80-specific imaging probes. Our results demonstrate that chemotherapy combined with GO(HPPH)-PEG PDT is a promising strategy for the treatment of tumors, especially those resistant to chemotherapy. Furthermore, TAM-targeted molecular imaging could potentially be used to predict the efficacy of combination therapy and select patients who would most benefit from this treatment approach. Cancer Res; 77(21); 6021–32. ©2017 AACR.