Maleimide as the PEG end-group promotes macrophage-targeted drug delivery of PEGylated nanoparticles in vivo by enhancing interaction with circulating erythrocytes

  • Biomaterials. 2023 Sep:300:122187. doi: 10.1016/j.biomaterials.2023.122187.
Xin Wang  1 ,  Xiandi Meng  2 ,  Kuirong Mao  3 ,  Hongmei Chen  4 ,  Xiuxiu Cong  2 ,  Feiqi Liu  5 ,  Jialiang Wang  2 ,  Shuhan Liu  2 ,  Yanbao Xin  2 ,  Ge Zhu  2 ,  Huizhu Tan  2 ,  Yong-Guang Yang  3 ,  Tianmeng Sun  6
Affiliations
  • 1. Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, Institute of Immunology, The First Hospital, Jilin University, Changchun, Jilin, China; National-local Joint Engineering Laboratory of Animal Models for Human Diseases, Changchun, Jilin, China; Medical Laboratory Center, Affiliated Hospital of Inner Mongolia Minzu University, Tongliao, Inner Mongolia, China.
  • 2. Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, Institute of Immunology, The First Hospital, Jilin University, Changchun, Jilin, China; National-local Joint Engineering Laboratory of Animal Models for Human Diseases, Changchun, Jilin, China.
  • 3. Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, Institute of Immunology, The First Hospital, Jilin University, Changchun, Jilin, China; International Center of Future Science, Jilin University, Changchun, Jilin, China; National-local Joint Engineering Laboratory of Animal Models for Human Diseases, Changchun, Jilin, China.
  • 4. Department of Oncology Chemotherapy, Shandong Provincial Hospital, Shandong First Medical University, Jinan, Shandong, China.
  • 5. Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, Institute of Immunology, The First Hospital, Jilin University, Changchun, Jilin, China.
  • 6. Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, Institute of Immunology, The First Hospital, Jilin University, Changchun, Jilin, China; International Center of Future Science, Jilin University, Changchun, Jilin, China; National-local Joint Engineering Laboratory of Animal Models for Human Diseases, Changchun, Jilin, China; State Key Laboratory of Supramolecular Structure and Materials, Jilin University, Changchun, Jilin, China. Electronic address: [email protected].
PMID: 37302279 DOI: 10.1016/j.biomaterials.2023.122187
Abstract

Radiotherapy (IR) is capable of enhancing antitumor immune responses. However, IR treatment also aggravates the infiltration of peripheral macrophages into the tumor, resulting in reversing the therapeutic effects of antitumor immunity. Thus, a strategy to effectively prevent tumor infiltration by macrophages may further improved the therapeutic efficacy of radiotherapy. Herein, we found that PEGylated solid lipid nanoparticles with maleimide as PEG end-group (SLN-PEG-Mal) show significantly enhanced adsorption onto RBCs through reacting with reactive sulfhydryl groups on RBCs' surface both in vitro and in vivo, and caused significant changes in the surface properties and morphology of RBCs. These RBCs adsorbed by SLN-PEG-Mal were rapidly removed from circulation due to efficient engulfment by reticuloendothelial macrophages, supporting the usefulness of SLN-PEG-Mal for macrophage-targeted drug delivery. While lacking the use of radioisotope tracing (considered the gold standard for PK/BD studies), our data align with the expected pathway of host defense activation through surface-loaded RBCs. Importantly, injection of paclitaxel-loaded SLN-PEG-Mal effectively inhibited the tumor-infiltration by macrophages, and significantly improved the antitumor immune responses in tumor-bearing mice treated with low-dose irradiation. This study provides insights into the effects of maleimide as PEG end-group on enhancing the interaction between PEGylated nanoparticles and RBCs and offers an effective strategy to inhibit tumor infiltration by circulating macrophages.

Keywords
Low-dose irradiation; Macrophage-targeted drug delivery; Maleimide; PEG end-Group; Red blood cells.
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