Indocyanine green and poly I:C containing thermo-responsive liposomes used in immune-photothermal therapy prevent cancer growth and metastasis

Abstract

Background Efficient cancer therapy is sought not only for primary tumor treatment but also for the prevention of metastatic cancer growth. Immunotherapy has been shown to prevent cancer metastasis by inducing antigen-specific immune responses. Indocyanine green (ICG) has a peak spectral absorption at about 800 nm, which makes it a photothermal reagent for direct treatment of solid tumors by photothermal therapy (PTT). Since PTT alone cannot fully induce antigen-specific immune response for prevention of cancer metastasis, the combination of PTT and immunotherapy has been developed as a new strategy of cancer treatment. Methods Thermal responsive liposomes (TRL) were synthesized by incorporating ICG into the lipid bilayer and encapsulating the water-soluble immune stimulatory molecule polyinosinic:polycytidylic acid (poly I:C) in the hydrophilic core. The poly I:C- and ICG-containing TRLs (piTRLs) were analyzed according to size, and their photothermal effect was evaluated following laser irradiation at 808 nm. Moreover, the temperature-dependent release of poly I:C was also measured. For cancer therapy, CT-26 (carcinoma) and B16 (melanoma) cells were subcutaneously inoculated to build the 1st transplanted tumor in BALB/c and C57BL/6 mice, respectively. These mice received a 2nd transplantation with the same cancer cells by intravenous inoculation, for evaluation of the anti-metastatic effects of the liposomes after PTT. Results Near-infrared (NIR) laser irradiation increased the temperature of piTRLs and effectively released poly I:C from the liposomes. The increased temperature induced a photothermal effect, which promoted cancer cell apoptosis and dissolution of the 1st transplanted tumor. Moreover, the released poly I:C from the piTRL induced activation of dendritic cells (DCs) in tumor draining lymph node (tdLN). Cancer cell apoptosis and DC-activation-mediated cancer antigen-specific immune responses further prevented growth of lung metastatic cancer developed following intravenous transplantation of cancer cells. Conclusion These results demonstrated the potential usage of a piTRL with laser irradiation for immuno-photothermal therapy against various types of cancer and their metastases. Electronic supplementary material The online version of this article (10.1186/s40425-019-0702-1) contains supplementary material, which is available to authorized users.

Cancer immunotherapy using a polysaccharide from Codium fragile in a murine model

“…Induction of cancer Ag-specific immune activation is one of the immunotherapy strategies used to treat cancer. 26,27,40 Although cancer cells over-express Ag candidate proteins, these proteins are not immunogenic as they are produced from the somatic cells without mutation. Therefore, immune stimulatory molecules or adjuvants are required to elicit cancer Ag-specific immune activation.…”

<p>Pathological Mechanism of Photodynamic Therapy and Photothermal Therapy Based on Nanoparticles</p>

“…9 Using branched poly (vinylamine) (PVA, MW=10k Da) as the best linker, the system was prepared on suitable thin layer hollow gold nanospheres (HAuNS) combined with indocyanine green (ICG) to maintain the fluorescence, 10 significantly enhanced intratumoral accumulation, boost photothermal conversion efficiency and synchronous PTT and PDT. 11 The second generation is carbon materials, for example, graphene and carbon nanorods, which have large photothermal conversion area but have poor absorption capacity under the NIR. 12 Wang et al proposed that an upconversion Magnetic Agent (FeCUPs) mediated by Hollow carbon spheres provides a dual-function platform of PTT and biological imaging for tumor elimination.…”

Harnessing nanomedicine to overcome the immunosuppressive tumor microenvironment

“…Anti-PD-L1 [179,180], anti-PD-1 [181][182][183]; poly (I:C) [184], CpG [185,186], LPS, GM-CSF, and anti-PD-1 [187]; CAR-T [188] Electrotherapy: Electrochemotherapy…”

“… Hyperthermia therapy combined with immune adjuvant, checkpoint regulator, or CAR-T therapy. Anti-PD-L1 [ 179 , 180 ], anti-PD-1 [ 181 – 183 ]; poly (I:C) [ 184 ], CpG [ 185 , 186 ], LPS, GM-CSF, and anti-PD-1 [ 187 ]; CAR-T [ 188 ] Electrotherapy: Electrochemotherapy Tumor-treating fields Local electroporation-facilitated drug uptake results in tumor cell death and release of tumor-associated antigens, activating immune reaction [ 189 ]; Mitotic disruption caused by alternating electric fields potentiates immunogenic cell death [ 190 ]. Electrochemotherapy combined with immune checkpoint blockade; Tumor-treating fields combined with immune checkpoint blockade.…”