Laser Immunotherapy in Combination with Perdurable PD-1 Blocking for the Treatment of Metastatic Tumors.
Lihua LuoChunqi ZhuHang YinMengshi JiangJunlei ZhangBing QinZhenyu LuoXiaoling YuanJie YangWei LiYong-Zhong DuJian YouPublished in: ACS nano (2018)
A convenient and feasible therapeutic strategy for malignant and metastatic tumors was constructed here by combining photothermal ablation (PTA)-based laser immunotherapy with perdurable PD-1 blockade immunotherapy. Hollow gold nanoshells (HAuNS, a photothermal agent) and AUNP12 (an anti PD-1 peptide, APP) were co-encapsulated into poly(lactic- co-glycolic) acid (PLGA) nanoparticles. Unlike monoclonal PD-1/PD-L1 antibodies, PD-1 peptide inhibitor shows lower cost and immunotoxicity but needs frequent administration due to its rapid clearance in vivo. Our data here showed that the formed HAuNS- and APP-loaded PLGA nanoparticles (AA@PN) could maintain release periods of up to 40 days for the peptide, and a single intratumoral injection of AA@PN could replace the frequent administration of free APP. After the administration of AA@PN and irradiation with a near-infrared laser at the tumor site, an excellent killing effect on the primary tumor cells was achieved by the PTA. The nanoparticles also played a vaccine-like role under the adjuvant of cytosine-phospho-guanine (CpG) oligodeoxynucleotide and generated a localized antitumor-immune response. Furthermore, sustained APP release with laser-dependent transient triggering could induce the blockage of PD-1/PD-L1 pathway to activate T cells, thus subsequently generating a systemic immune response. Our data demonstrated that the PTA combined with perdurable PD-1 blocking could efficiently eradicate the primary tumors and inhibit the growth of metastatic tumors as well as their formation. The present study provides a promising therapeutic strategy for the treatment of advanced cancer with metastasis and presents a valuable reference for obtaining better outcomes in clinical cancer immunotherapy.
Keyphrases
- immune response
- drug delivery
- squamous cell carcinoma
- small cell lung cancer
- advanced cancer
- cancer therapy
- drug release
- early stage
- photodynamic therapy
- electronic health record
- dendritic cells
- toll like receptor
- dna methylation
- gene expression
- mass spectrometry
- type diabetes
- insulin resistance
- wastewater treatment
- cerebral ischemia
- skeletal muscle
- brain injury
- machine learning
- molecularly imprinted
- atrial fibrillation
- walled carbon nanotubes