An on‐Demand Oxygen Nano‐vehicle Sensitizing Protein and Nucleic Acid Drug Augment Immunotherapy
Abstract
Abstract Hypoxia severely limits the antitumor immunotherapy for breast cancer. Although efforts to alleviate tumor hypoxia and drug delivery using diverse nanostructures achieve promising results, the creation of a versatile controllable oxygen‐releasing nano‐platform for co‐delivery with immunostimulatory molecules remains a persistent challenge. To address this problem, a versatile oxygen controllable releasing vehicle PFOB@F127@PDA (PFPNPs) is developed, which effectively co‐delivered either protein drug lactate oxidase (LOX) or nucleic acids drug unmethylated cytosine‐phosphate‐guanine oligonucleotide (CpG ODNs). Upon photothermal heating, this platform triggered oxygen release, thereby augmenting LOX‐mediated lactate detection rates, and improving T cells infiltrating and cytokine expression. Moreover, under an oxygenated tumor microenvironment (TME), PFPNPs co‐delivered with CpG ODNs effectively reprogrammed the immunosuppressive TME by repolarizing macrophages to an M1‐like phenotype, promoting dendritic cells maturation, and increasing tumor‐infiltrating T cells while decreasing the ratio of regulatory T cells (Tregs). Our study demonstrated that this controlled oxygen‐releasing platform possessed adaptive drug‐loading capabilities to meet varied immunotherapeutic demands in clinical settings.
Article Details
Authors (14)
Sidi Zhang
State Key Laboratory of Systems Medicine for Cancer Shanghai Cancer Institute. Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200032 P. R. China
Xinghui Wang
College of Physics and Information Engineering, Institute of Micro–Nano Devices and Solar Cells, Fuzhou University
Xiaojing Chen
Duohuo Shu
Quankun Lin
State Key Laboratory of Systems Medicine for Cancer Shanghai Cancer Institute. Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200032 P. R. China
Hanbing Zou
State Key Laboratory of Systems Medicine for Cancer Shanghai Cancer Institute. Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200032 P. R. China
Jialin Dong
Anshan Ziyu Laser Technology Co., Ltd. 4 , AnShan 114044,
Bing Wang
Qianyun Tang
State Key Laboratory of Systems Medicine for Cancer Shanghai Cancer Institute. Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200032 P. R. China
Huishan Li
State Key Laboratory of Systems Medicine for Cancer Shanghai Cancer Institute. Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200032 P. R. China
Xiaoxiang Chen
Jun Pu
Bin Gu
Peifeng Liu
State Key Laboratory of Systems Medicine for Cancer Shanghai Cancer Institute Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai P. R. China