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Highly efficient cascading synergy of cancer photo-immunotherapy enabled by engineered graphene quantum dots/photosensitizer/CpG oligonucleotides hybrid nanotheranostics

Wu, Chunhui, Guan, Xiaotian, Xu, Jiming, Zhang, Yingxue, Liu, Qiuyue, Tian, Yuan, Li, Shun, Qin, Xiang, Yang, Hong, Liu, Yiyao
Biomaterials 2019 v.205 pp. 106-119
T-lymphocytes, Toll-like receptor 9, cytokines, dendritic cells, fluorescence, gadolinium, graphene, image analysis, immunotherapy, irradiation, magnetic resonance imaging, magnetism, mammary neoplasms (animal), mice, models, nanocomposites, nanoparticles, neoplasm cells, oligodeoxyribonucleotides, photosensitizing agents, polymers, quantum dots, secretion
Currently, photoimmunotherapy based on a theranostic nanoplatform emerges as a promising modality in advanced cancer therapy. In this study, a new type of versatile nanoassemblies (denoted as PC@GCpD(Gd)) was rationally designed by integrating the polydopamine stabilized graphene quantum dots (GQD)-photosensitizer nanocomposites (denoted as GCpD), immunostimulatory polycationic polymer/CpG oligodeoxynucleotide (CpG ODN) nanoparticles (denoted as PC) and Gd3+/Cy3 imaging probes for dual magnetic resonance/fluorescence imaging-guided photoimmunotherapy. PC@GCpD(Gd) effectively killed the tumor cells through the amplified photothermal and photodynamic effects mediated by GCpD, and contemporaneously delivered CpG ODN to the targeted endosomal Toll-like receptor 9 (TLR9) to continuously stimulate the secretion of proinflammatory cytokines and the maturation of dendritic cells, thereby resulting in the activation and infiltration of T lymphocytes. As a result, PC@GCpD(Gd) achieved robust inhibition efficiency to almost completely suppress the EMT6 murine mammary cancer model under laser irradiation, implying the superior synergy of combined photoimmunotherapy. Moreover, the in vivo delivery and biodistribution of PC@GCpD(Gd) could be tracked using the high-quality bimodal magnetic resonance imaging/fluorescence imaging. This study highlighted the potent prospect of hybrid PC@GCpD(Gd) nanoassemblies for precise cancer photoimmunotherapy with a cascading effect.