Table 3.

Summary of design strategies for SNA's programmable structure on maximizing immune system activation.

Structure	Variables in the structure	Adjuvant	Antigen	modol	Outcomes	Ref
L -SNA	Differential hydrophobic anchors between nucleic acids and liposomes (lipid-tail or cholesterol-tail)	CpG-1826	None	RAW-Blue macrophages	The structures utilizing lipid tail-anchored nucleic acids in LSNA have greater stability as well as greater ability to activate TLR receptors than those utilizing cholesterol-anchored nucleic acids.	[207]
L -SNA	Diacyl lipid tail	CpG-1826	Py8119 TNBC cells lysates	Orthotopic mouse models of 4T1 & Py8119	The use of DPPC with high Tc value as a lipid tail could improve the serum stability of L-SNA as well as the ability to activate immunity, with obvious anti-tumor effects, and inhibit the lung metastasis of TNBC cells.	[202]
L -SNA	The Linker between antigen and SNA(Whether or not it can be cracked)	CpG	Gp100 (KVPRNQDWL)	DC cells derived from bone marrow	A cleavable traceless linker between antigen and SNA enhances activation of T cells.	[203]
L -SNA	The Linker between peptide antigens and SNAs(The rate of cleavage)	CpG	OVA-1	C57BL/6&OT-1 mouse splenocytes	The cleavable Linker and the ability to rapidly release antigen can enhance the immunizing effect of SNA.	[204]
L -SNA	Location of antigen and adjuvant	CpG	Prostate cancer peptide	Syngeneic mouse models of prostate cancer	HM SNAs, which can simultaneously present antigen and adjuvant on the surface, are capable of inducing stronger anti-tumor immune responses than EM SNAs, in which the SNA core encapsulates the antigen.	[194]
L -SNA	Location of OVA1 and OVA2 on the SNA & the way of delivery for both antigens OVA1 and OVA2.	CpG	OVA1&OVA2	DC cells derived from bone marrow& C57BL/6	Simultaneous delivery of both antigens with the same SNA induced stronger T cell activation than delivery of two SNAs separately. Moreover, the structure of core-coated OVA2 and externally crosslinked OVA1 significantly improved the tumor suppression effect than the structure of core-coated OVA1 and externally crosslinked OVA2.	[175]
L -SNA	Categories of nucleic acids loaded on the surface of LSNA	CpG-A&CpG-B	None	DC cells derived from bone marrow	LSNA containing two-component CpG activated the maturation of DC cells more than mixtures of CpG-A and CpG-B and single-component LSNA containing CpG-A or CpG-B.	[205]