Engineering Oxaliplatin Prodrug Nanoparticles for Second Near-Infrared Fluorescence Imaging-Guided Immunotherapy of Colorectal Cancer.
Qiurong ZhuFang SunTianliang LiMengxue ZhouJiayi YeAiyan JiHui WangChunyong DingHao ChenZhiai XuHaijun YuPublished in: Small (Weinheim an der Bergstrasse, Germany) (2021)
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.
Keyphrases
- fluorescence imaging
- photodynamic therapy
- cancer therapy
- drug release
- immune response
- drug delivery
- cell death
- end stage renal disease
- chronic kidney disease
- ejection fraction
- fluorescent probe
- newly diagnosed
- squamous cell carcinoma
- toll like receptor
- bone marrow
- prognostic factors
- papillary thyroid
- radiation therapy
- high glucose
- wastewater treatment
- peritoneal dialysis
- stress induced
- pseudomonas aeruginosa
- rectal cancer
- patient reported
- drug resistant