Photothermal-Activatable Fe3O4 Superparticle Nanodrug Carriers with PD-L1 Immune Checkpoint Blockade for Anti-metastatic Cancer Immunotherapy.

Abstract

Checkpoint blockade immunotherapy has shown great potential in clinical cancer therapy, but the body's systemic immune must be fully activated and generates a positive tumor-specific immune cell response. In this work, we demonstrate the design of the immune-adjuvant nanodrug carriers on the basis of poly(ethylene glycol)- block-poly(lactic- co-glycolic acid) copolymer-encapsulated Fe3O4 superparticles (SPs), in which imiquimod (R837), a kind of Toll-like receptor 7 agonist, is loaded. The nanodrug carriers are defined as Fe3O4-R837 SPs. The multitasking Fe3O4-R837 SPs can destroy the 4T1 breast tumor by photothermal therapy (PTT) under near-infrared laser irradiation to generate the tumor-associated antigens because of the high efficiency of tumor magnetic attraction ability and photothermal effect. The PTT also triggers the release of R837 as the adjuvant to trigger a strong antitumor immune response. By further combining with the checkpoint blockade adjusted by programmed death ligand 1 (PD-L1) antibody, the Fe3O4-R837 SP-involved PTT cannot only eliminate the primary tumors but also prevent tumor metastasis to lungs/liver. Meanwhile, this synergistic therapy also shows abscopal effects by completely inhibiting the growth of untreated distant tumors through effectively triggering the tumors infiltrated by CD45+ leukocytes. Such findings suggest that Fe3O4-R837 SP-involved PTT can significantly potentiate the systemic therapeutic efficiency of PD-L1 checkpoint blockade therapy by activating both innate and adaptive immune systems in the body.

• Authors: Rui Ge, Cangwei Liu, Xue Zhang, Wenjing Wang, Binxi Li, Jie Liu, Yi Liu, Hongchen Sun, Daqi Zhang, Yuchuan Hou, Hao Zhang, Bai Yang
• Journal: ACS applied materials & interfaces (ACS Appl Mater Interfaces) Vol. 10 Issue 24 Pg. 20342-20355 (Jun 20 2018) ISSN: 1944-8252 [Electronic] United States
• PMID: 29878757 (Publication Type: Journal Article)

Chemical References

• Adjuvants, Immunologic
• Antigens, Neoplasm
• B7-H1 Antigen
• CD274 protein, human
• Ferric Compounds
• ferric oxide

Topics

• Adjuvants, Immunologic
• Antigens, Neoplasm
• B7-H1 Antigen
• Breast Neoplasms
• Ferric Compounds (chemistry)
• Humans
• Immunotherapy
• Phototherapy