Table 2.

Summary of SNA working strategies for tumor immunotherapy.

Adjuvant	Antigens or drugs	Disease model	Innovative Strategies	Modes of action	Outcomes	Ref.
CpG	Pembrolizumab/cemiplimab	Advanced MCC/CSCC patients	AST-OO8, an SNA that activates TLR9, in combination with pembrolizumab for the treatment of MCC or with cemiplimab for the treatment of CSCC.	AST-OO8 increases th1-type cytokines, which in turn activate T cells and NK cells; pembrolizumab and cemiplimab bind specifically to PD-1	Tumor regression was observed and, at the site of the lesion, increased infiltration of toxic immune cells	[189]
dsDNA	None	Glioblastoma	Nucleic acids can be delivered to intracranial tumor sites through the nasal cavity using SNA transported dsDNA.	Binding of dsDNA to cGAS induces endogenous CDN production, which in turn stimulates interferon gene-stimulating proteins to activate innate immunity for tumor treatment.	Tumors have good tolerance to STING-SNA, and fewer doses can delay tumor growth and improve survival.	[196]
CpG	Prostate peptide antigens (PSA; PSMA; PAP)	C57BL6 mouse prostate cancer transplantation tumor model	Co-delivery of SNA to adjuvants and peptide antigens enhances DC activation, spanning the current limitations of immunotherapy against weakly immunogenic tumors using only antigens such as OVA.	Class B CpG matures DCs to produce Th1 cytokines such as IL-12; peptide antigens activate antigen-specific T-cell immune responses in vivo	Co-delivery of CpG and antigen using SNA produced a stronger immune response than delivery of a simple mixture of CpG and antigen, and structural activation of immunity by antigen and adjuvant on the surface of SNA was most effective.	[194]
CpG-1826	Lysates from TNBC cells (Oxidized or non-oxidized)	EMT6 model of TNBC; Py230 and Py8119 models of TNBC	Use of oxidized tumor cell lysates as antigens in SNA	SNA co-delivery of lysates and adjuvants can increase cellular uptake and bioavailability	Lys-SNAs were more potent than CpG and lysates co-mixtures in delaying tumor growth in Py230 and Py8119 models; OxLys-SNAs showed potent anti-tumor effects in EMT6 model of TNBC.	[193]
CpG	DOX	Tumor-bearing E.G7-OVA mice	Ability to generate tumor-specific antigens, effectively avoiding off-target effects	Using DOX to generate ICD effects and CpG to enhance ICD-generated immune responses	Enhances CD8+ and CD4+ amplification, delays tumor growth and prolongs survival of tumor-bearing mice	[192]
CpG	Au&αPD-L1	Tumor-bearing 4T1 mice	SNA acts as both a radiosensitizer and an immunotherapeutic agent.	Gold nanoparticles of SNA act as radiosensitizers; RT causes tumor cells to produce ICD; SNA captures antigen to form an in situ vaccine and works synergistically with αPD-L1.	A potent anti-tumor effect was obtained, completely inhibiting tumor growth.	[198]