Co-Delivery of Doxorubicin and Anti-PD-L1 Peptide in Lipid/PLGA Nanocomplexes for the Chemo-Immunotherapy of Cancer.
Nan ZhangJing LiWen-Xia GaoWangwei ZhuJianqin YanZiyun HeLi LiFang WuYuji PuBin HePublished in: Molecular pharmaceutics (2022)
The combined delivery of chemotherapeutics with checkpoint inhibitors of the PD-1/PD-L1 pathway provides a new approach for cancer treatment. Small-molecule peptide inhibitors possess short production cycle, low immunogenicity, and fewer side effects; however, their potential in cancer therapy is hampered by the rapid biodegradation and a nanocarrier is needed for efficient drug delivery. Herein, anticancer drug doxorubicin (DOX) and PD-L1 inhibitor peptide P-12 are co-loaded by a lipid polymer nanocomplex based on poly(lactic- co -glycolic acid) (PLGA) and DSPE-PEG. Octaarginine (R8)-conjugated DSPE-PEG renders the LPN efficient internalization by cancer cells. The optimal nanomedicine LPN-30-R8 2K @DP shows a diameter of 125 nm and a DOX and P-12 loading content of 5.0 and 6.2%, respectively. LPN-30-R8 2K @DP exhibits good physiological stability and enhanced cellular uptake by cancer cells. It successfully induces immunogenic cell death and PD-L1 blockade in CT26 cancer cells. The in vivo antitumor study further suggests that co-loaded nanomedicine efficiently suppresses CT26 tumor growth and elicits antitumor immune response. This study manifests that lipid polymer nanocomplexes are promising drug carriers for the efficient chemo-immunotherapy of cancer.
Keyphrases
- drug delivery
- cancer therapy
- small molecule
- drug release
- cell death
- immune response
- photodynamic therapy
- papillary thyroid
- computed tomography
- fatty acid
- image quality
- signaling pathway
- radiation therapy
- risk assessment
- magnetic resonance imaging
- squamous cell carcinoma
- contrast enhanced
- positron emission tomography
- dna damage
- toll like receptor
- dual energy
- cell cycle
- adverse drug
- loop mediated isothermal amplification
- oxidative stress
- locally advanced
- cell proliferation
- pet ct
- rectal cancer