DNA nanotechnology-based composite-type gold nanoparticle-immunostimulatory DNA hydrogel for tumor photothermal immunotherapy

Abstract

Success of tumor photothermal immunotherapy requires a system that induces heat stress in cancer cells and enhances strong anti-tumor immune responses. Here, we designed a composite-type immunostimulatory DNA hydrogel consisting of a hexapod-like structured DNA (hexapodna) with CpG sequences and gold nanoparticles. Mixing of the properly designed hexapodna and oligodeoxynucleotide-modified gold nanoparticles resulted in the formation of composite-type gold nanoparticle-DNA hydrogels. Laser irradiation of the hydrogel resulted in the release of hexapodna, which efficiently stimulated immune cells to release proinflammatory cytokines. Then, EG7-OVA tumor-bearing mice received an intratumoral injection of a gold nanoparticle-DNA hydrogel, followed by laser irradiation at 780 nm. This treatment increased the local temperature and the mRNA expression of heat shock protein 70 in the tumor tissue, increased tumor-associated antigen-specific IgG levels in the serum, and induced tumor-associated antigen-specific interferon-γ production from splenocytes. Moreover, the treatment significantly retarded the tumor growth and extended the survival of the tumor-bearing mice.

Nanoparticle‐Mediated Immunogenic Cell Death Enables and Potentiates Cancer Immunotherapy

“…An umber of inorganic nano-agents (e.g.A uNPs and nanoshells, [37] CuS NPs, [38] GO, [39] MoS 2 nanosheets, [40] or carbon nanotubes [41] )w ith intrinsic capacity for NIR light absorption have been developed to deliver thermal energy and immunoadjuvants.Y ata et al modified AuNPs with CpG oligodeoxynuleotides and then mixed them with ah exapodlike structured DNAcontaining CpG sequences,obtaining an immunostimulatory Au-DNAh ydrogel. Intratumoral injection of the Au-DNAh ydrogel followed by laser irradiation increased the local temperature and HSP70 mRNAl evels in the tumor,i mproved TAA-specific IgG levels in the serum, and induced TAA-specific IFN-g production in splenocytes, significantly retarding tumor growth and extending the survival time of tumor-bearing mice.…”

“…Intratumoral injection of the Au-DNAh ydrogel followed by laser irradiation increased the local temperature and HSP70 mRNAl evels in the tumor,i mproved TAA-specific IgG levels in the serum, and induced TAA-specific IFN-g production in splenocytes, significantly retarding tumor growth and extending the survival time of tumor-bearing mice. [37] Guo et al designed chitosan-coated hollow CuS NPs containing CpG,w hich could break down after laser excitation, reassemble,a nd transform into polymer complexes,i mproving CpG tumor retention, effectively eliminating the primary tumor and simultaneously inhibiting the growth of distant untreated tumors. [38] Small molecule photothermal agents can also be coloaded with immunostimulators into liposomes or polymeric NPs for effective combination of PTT and immunotherapy.Li et al coated ah yaluronic acid (HA)-CpG conjugate onto fluorophore (IR-7)-loaded liposomes to activate and increase tumor infiltration of DCs and CD8 + Tcells,thereby eradicating tumors in mice and inhibiting tumor metastasis.…”

Nanoparticle‐Based Nanomedicines to Promote Cancer Immunotherapy: Recent Advances and Future Directions

“…In this Review, bioadjuvants just refer to the ligands for pattern recognition receptors (PRR), including toll‐like receptors (TLRs), NOD‐like receptors (NLRs), RIG‐I‐like receptors (RLRs), and C‐type lectin receptors (CLRs), which predominantly target the antigen‐presenting cells, inducing the innate immunity, and consequently influencing the adaptive immune responses. Among numerous available bioadjuvants, TLR agonists have been intensely investigated, such as CpG, poly(I:C), monophosphoryl lipid A (MPLA), lipopolysaccharide (LPS), and resiquimod (R848), which show higher efficiency in the form of delivery nanovectors than free soluble form . Interestingly, a polymeric nanocomplex encapsulating low dose of paclitaxel, a kind of anticancer drug, displayed an adjuvant function to hinder immunologic escape and activate cancer immunotherapy …”

Nanoparticle‐based photothermal and photodynamic immunotherapy for tumor treatment

“…An effective method is to use immunoadjuvants, which are a class of substances that play a supporting role in non-specific alteration or enhance the specific immune response to antigens. 54 Single-walled carbon nanotube (SWNT)based PTT can induce a significant immune response, that is, increasing DC infiltration and maturation rate and stimulating the secretion of pro-inflammatory cytokines IL-1β, IL-12, IL-6 and TNF-α. This effect not only inhibits the recurrence of the primary tumor but also slows down or even eradicates the growth of metastatic tumors.…”

“…The hydrogels increase the amount of antitumor inflammatory mediators TNF-α, IL-6 and IFN-γ in tumors or splenocytes, ultimately inhibiting tumor growth and prolonging survival time. 54 Single-walled carbon nanotube (SWNT)based PTT can induce a significant immune response, that is, increasing DC infiltration and maturation rate and stimulating the secretion of pro-inflammatory cytokines IL-1β, IL-12, IL-6 and TNF-α. 47 The probable cause is that SWNTs can induce an adjuvant effect and therefore amplify immunostimulatory signals after PTT.…”