Engineering Oxaliplatin Prodrug Nanoparticles for Second Near‐Infrared Fluorescence Imaging‐Guided Immunotherapy of Colorectal Cancer. Issue 13 (10th March 2021)

• Record Type: Journal Article
• Authors: Zhu, Qiurong; Sun, Fang; Li, Tianliang; Zhou, Mengxue; Ye, Jiayi; Ji, Aiyan; Wang, Hui; Ding, Chunyong; Chen, Hao; Xu, Zhiai; Yu, Haijun
• Is Part Of: Small. Volume 17:Issue 13(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-03-10
• Subjects: colorectal cancer -- combinatory immunotherapy -- immunogenic cell death -- prodrug nanoparticles -- second near‐infrared fluorescence imaging; Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.202007882
• Languages: English
• ISSNs: 1613-6810

Abstract

Abstract: Colorectal cancer (CRC) ranks as the third common and the fourth lethal cancer type worldwide. Immune checkpoint blockade therapy demonstrates great efficacy in a subset of metastatic CRC patients, but precise activation of the antitumor immune response at the tumor site is still challenging. Here a versatile prodrug nanoparticle for second near‐infrared (NIR‐II) fluorescence imaging‐guided combinatory immunotherapy of CRC is reported. The prodrug nanoparticles are constructed with a polymeric oxaliplatin prodrug (PBOXA) and a donor–spacer–acceptor–spacer–donor type small molecular fluorophore TQTCD. The later displays large Stokes shift (>300 nm), fluorescence emission over 1000 nm, and excellent photothermal conversion performance for NIR‐II fluorescence imaging‐guided photothermal therapy (PTT). The prodrug nanoparticles show seven times higher intratumoral OXA accumulation than free oxaliplatin. TQTCD‐based PTT and PBOXA‐induced chemotherapy trigger immunogenic cell death of the tumor cells and elicit antitumor immune response in a spatiotemporally controllable manner. Further combination of the prodrug nanoparticle‐based PTT/chemotherapy with programmed death ligand 1 blockade significantly promotes intratumoral infiltration of the cytotoxic T lymphocytes and eradicates the CRC tumors. The NIR‐II fluorescence imaging‐guided immunotherapy may provide a promising approach for CRC treatment. Abstract : Versatile oxaliplatin prodrug nanoparticles are engineered for second near‐infrared (NIR‐II) fluorescence imaging‐guided immunotherapy of colorectal cancer. Under the guidance of NIR‐II fluorescence imaging, the prodrug nanoparticles can perform combinatory immunotherapy by inducing immunogenic cell death of the tumor cells. In combination with anti‐PD‐L1 antibody, the prodrug nanoparticles completely eradicate the colorectal cancer tumor xenograft by combating immune evasion.