Second near-infrared photothermal-amplified immunotherapy using photoactivatable composite nanostimulators

Haitao Sun,Peike Peng,Jianke Li,Tianzhu Yu,Yu Luo,Xiaolin Wang,Yangyang Lei,Xin Li,Xiuhui Wang,Dalong Ni

doi:10.1186/s12951-021-01197-5

Abstract

BackgroundThe construction of a nanoimmune controlled-release system that spatiotemporally recognizes tumor lesions and stimulates the immune system response step by step is one of the most potent cancer treatment strategies for improving the sensitivity of immunotherapy response.ResultsHere, a composite nanostimulator (CNS) was constructed for the release of second near-infrared (NIR-II) photothermal-mediated immune agents, thereby achieving spatiotemporally controllable photothermal-synergized immunotherapy. CNS nanoparticles comprise thermosensitive liposomes as an outer shell and are internally loaded with a NIR-II photothermal agent, copper sulfide (CuS), toll-like receptor-9 (TLR-9) agonist, cytosine-phospho-guanine oligodeoxynucleotides, and programmed death-ligand 1 (PD-L1) inhibitors (JQ1). Following NIR-II photoirradiation, CuS enabled the rapid elevation of localized temperature, achieving tumor ablation and induction of immunogenic cell death (ICD) as well as disruption of the lipid shell, enabling the precise release of two immune-therapeutical drugs in the tumor region. Combining ICD, TLR-9 stimulation, and inhibited expression of PD-L1 allows the subsequent enhancement of dendritic cell maturation and increases infiltration of cytotoxic T lymphocytes, facilitating regional antitumor immune responses.ConclusionCNS nanoparticle-mediated photothermal-synergized immunotherapy efficiently suppressed the growth of primary and distant tumors in two mouse models and prevented pulmonary metastasis. This study thus provides a novel sight into photo-controllably safe and efficient immunotherapy.Graphical

Highlights

The construction of a nanoimmune controlled-release system that spatiotemporally recognizes tumor lesions and stimulates the immune system response step by step is one of the most potent cancer treatment strategies for improving the sensitivity of immunotherapy response
Hydrophobic JQ1 and hydrophilic Copper sulfide (CuS) and CpG were encapsulated into temperature-responsive liposomes through hydrophobic and π–π stacking interactions
The results showed that cells treated with diverse composite nanostimulator (CNS) nanoparticles plus NIRII light all decreased with elevating CuS concentrations (Fig. 2c)

Summary

Introduction

The construction of a nanoimmune controlled-release system that spatiotemporally recognizes tumor lesions and stimulates the immune system response step by step is one of the most potent cancer treatment strategies for improving the sensitivity of immunotherapy response. Tumor immunotherapy that mobilizes immune cells to fight malignant tumors is a promising therapeutic approach [1, 2] Diverse immunotherapy strategies, such as the modulation of immune checkpoint inhibitors (ICBs) against programmed death/ligand 1 (PD-1/ PD-L1) [3, 4], cytotoxic T lymphocyte-associated protein 4 (CTLA-4) [5, 6], and adoptive T cell transfer [7,8,9], have shown satisfactory prospects in clinical studies. Several immune drugs, such as PD-L1 inhibitors and CTLA-4 inhibitors, have been approved by the U.S Food and Drug Administration (FDA) and successfully commercialized [10]. The use of clinical immunotherapy with higher efficiency and safety is necessary

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Conclusion