ABSTRACT
Using metal coordination to assemble carbon nanodots (CND) into clusters can enhance their photophysical properties for applications in sensing and biomedicine. Water-soluble clusters of CNDs are prepared by one-step microwave synthesis starting from ethylenediaminetetraacetic acid, ethylenediamine and MnCl2·4H2O as precursors. Transmission electron microscopy and powder X-Ray diffraction techniques indicate that the resulting clusters form spherical particles of 150 nm constituted by amorphous CNDs joined together with Mn ions in a laminar crystalline structure. The nanomaterial assemblies show remarkable fluorescence quantum yields (0.17-0.20) and magnetic resonance imaging capability (r1 = 2.3-3.8 mM-1.s-1). In addition, they can be stabilized in aqueous solutions by phosphate ligands, providing a promising dual imaging platform for use in biological systems.
ABSTRACT
Encouraging results are emerging from systems that exploit Toll like receptor (TLR) signaling, nanotechnology, checkpoint inhibition and molecular imaging for cancer immunotherapy. A major remaining challenge is developing effective, durable and tumour-specific immune responses without systemic toxicity. Here, we report a simple and versatile system based on synergistic activation of immune responses and direct cancer cell killing by combined TLR ligation using polyIC as TLR3 and imiquimod (R837) as TLR7 agonist, in combination with the model antigen ovalbumin (OVA) and phospholipid micelles loaded with zinc-doped iron oxide magnetic nanoparticles (MNPs). The combination of TLR agonists triggered a strong innate immune response in the lymph nodes (LNs) without systemic release of pro-inflammatory cytokines. The vaccines showed excellent efficacy against aggressive B16-F10 melanoma cells expressing OVA, which was improved with immune checkpoint abrogation of the immunosuppressive programmed death-ligand 1 (PD-L1) at the level of the cancer cells. By magnetic resonance (MR) and nuclear imaging we could track the vaccine migration from the site of injection to LNs and tumour. Overall, we show this synergistic TLR agonists and their combination with MNPs and immune checkpoint blockade to have considerable potential for preclinical and clinical development of vaccines for cancer immunotherapy.
Subject(s)
Imiquimod/pharmacology , Immunotherapy , Magnetite Nanoparticles/chemistry , Nanotechnology , Neoplasms/immunology , Neoplasms/therapy , Poly I-C/pharmacology , Animals , Antigen-Presenting Cells/drug effects , Antigen-Presenting Cells/metabolism , Cancer Vaccines/immunology , Cell Death/drug effects , Cell Line , Cell Line, Tumor , Cell Movement/drug effects , Drug Synergism , Endocytosis/drug effects , Endosomes/drug effects , Endosomes/metabolism , Imiquimod/therapeutic use , Immunity, Innate/drug effects , Immunization , Lymph Nodes/drug effects , Lymph Nodes/pathology , Melanoma/immunology , Melanoma/pathology , Melanoma/therapy , Mice, Inbred C57BL , Neoplasms/diagnosis , Neoplasms/pathology , Phospholipids/chemistry , Poly I-C/therapeutic use , Polyethylene Glycols/chemistryABSTRACT
The fac-[(99m)Tc(OH2)3(CO)3](+) complex reacts with QD-filled micelles to create a bimodal SPECT-optical imaging probe which upon visible light irradiation generates cisplatin from an inert Pt(IV) prodrug.
Subject(s)
Antineoplastic Agents/administration & dosage , Cisplatin/administration & dosage , Micelles , Optical Imaging/methods , Prodrugs/administration & dosage , Quantum Dots , Tomography, Emission-Computed, Single-Photon/methods , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cisplatin/chemistry , Cisplatin/pharmacology , Drug Delivery Systems , Humans , Light , Luminescence , Male , Prodrugs/chemistry , Prodrugs/pharmacology , Prostate/drug effects , Prostatic Neoplasms/drug therapyABSTRACT
Magnetite-filled micelles capture fac-[M(OH(2))(3)(CO)(3)](+) complexes (M = (99m)Tc, Re), creating versatile self-assembled constructs for multimodal SPECT/MR/optical imaging and radiopharmaceutical guided delivery.
