. 2025 Aug 22;7(19):5905–5931. doi: 10.1039/d5na00323g

Table 5. Summary of studies reporting antibody-decorated LBNPs encapsulating therapeutic RNAs.

Type of loaded RNA	Type of antibody used for functionalization	Type of lipid-based nanocarrier	Linker	Lipid composition	Size (nm) and PDI	ZP (mV)	Target cells	Advantages	Reference
siRNA	αHB-EGF	cLNP	DSPE-PEG-Mal	DOPE, cholesterol, DMPG, and DSPE-PEG	∼170	∼6	MDA-MB-231 cancer cell line	They prolonged circulation, with plasma retention 6 to 9 times higher than unmodified LNP-siRNA. Tumor accumulation was also higher. They also penetrated more deeply within tumor tissue, due to specific binding to HB-EGF expressed on MDA-MB-231 tumor cells	87
siRNA	αHB-EGF	cLNP	DSPE-PEG-Mal	DOPE, cholesterol, DMPG, and DSPE-PEG	∼0.28	∼6	MDA-MB-231 cancer cell line		87
Anti-miRNA 27a	Anti-GPC3	Cationic switchable LNPs	Thiol-maleimide chemistry (DSPE-PEG-MAL)	CSL3, DSPC, DSPE-PEG2000, DSPE-PEG2000-MAL, and cholesterol	∼165	25	HepG2 cell line	They showed an IC₅₀ of 0.71 μg mL⁻¹. Additionally, 76% of SRF was released at acidic pH within 24 hours, compared to only 38% at physiological pH, supporting targeted intracellular delivery	32
Anti-miRNA 27a	Anti-GPC3	Cationic switchable LNPs	Thiol-maleimide chemistry (DSPE-PEG-MAL)	CSL3, DSPC, DSPE-PEG2000, DSPE-PEG2000-MAL, and cholesterol	0.115	25	HepG2 cell line		32
miRNA 130a	PD-L1 antibody	Liposomes	Thiol-maleimide chemistry (DSPE-PEG2000-Mal)	DSPC, DSPE-PEG2000, cholesterol, DSPE-PEG2000-Mal, and DOTAP	∼168	∼21.5	HGC27 cancer cell line	Both reduced Ki67⁺ cells and increased TUNEL⁺ cells were witnessed in immunohistochemical analysis, suggesting increased apoptosis. Regarding the liposomes' release profile, 43% were released at acidic pH compared to 26% only at physiological pH. MTT assay showed a concentration-dependent inhibition of the HGC27 viability	88
miRNA 130a	PD-L1 antibody	Liposomes	Thiol-maleimide chemistry (DSPE-PEG2000-Mal)		0.128	∼21.5	HGC27 cancer cell line		88
mRNA	αPV1 antibody	LNP	Thiol-maleimide chemistry (DSPE-PEG-Mal)	Dlin-MC3-DMA ionizable lipid, DSPC, cholesterol, DMG-PEG, and DSPE-PEG-Mal	∼160	−5.43	Tested in vivo only on female Balb-c (BALB/cAnNHsd) mice	Decorating LNPs with αPV1 antibody promoted a 14-fold increase in lung accumulation. Confocal imaging confirmed the endothelial localization of αPV1 LNPs in lung tissue; meanwhile, mRNA translation in the lungs was even more remarkable	89
mRNA	αPV1 antibody	LNP	Thiol-maleimide chemistry (DSPE-PEG-Mal)		0.222	−5.43	Tested in vivo only on female Balb-c (BALB/cAnNHsd) mice		89
sgRNA PLK1	Anti-EGFR antibody	LNP	ASSET linker system	Ionizable lipids (lipids 1, 6, 8, and 10, DSPC, cholesterol, DMG-PEG, and DSPE-PEG)	71–80	N/A	OV8 cell line	Upon tagging the LNP with anti-EGFR antibodies, 3-fold higher tumor accumulation compared to isotype controls and selective uptake into disseminated ovarian tumors was detected. RNA release and expression were very rapid, with therapeutic effects observed within 48 hours. PLK1 gene editing achieved an average of 82% efficacy in tumor cells and remained less than 1% in normal ones. Consequently, more efficient tumor growth inhibition and an 80% increase in patients' survival rate were achieved	91
sgRNA PLK1	Anti-EGFR antibody	LNP	ASSET linker system		0.2	N/A	OV8 cell line		91
siRNA E6	Anti-EGFR antibody	LNP	ASSET linker system (recombinant protein linker)	DSPC, DMG-PEG, (DSPE-mPEG), cholesterol, and cationic lipid 10	∼90	∼−5	FaDu, 2A3, UMSCC-104, and UPCI: SCC090 cell lines	LNPs decreased tumor volume by 50% and restricted tumor progression. They demonstrated significant RNA release and gene silencing, as evidenced by the low levels of E6 mRNA and reduced expression of E7 protein at 48 and 72 hours post-treatment	92
siRNA E6	Anti-EGFR antibody	LNP	ASSET linker system (recombinant protein linker)		∼0.1	∼−5	FaDu, 2A3, UMSCC-104, and UPCI: SCC090 cell lines		92
mRNAmCherry	Anti-CD3 antibody	LNP	Thiol-maleimide chemistry (DSPE-PEG5000-Mal)	Cationic lipid DLin-MC3-DMA, DSPC, DSPE-PEG2000, DSPE-PEG5000-Mal, DSPE-PEG2000-Cyanine7, and cholesterol	71.2	∼−9	Jurkat T-cell leukemia cells	LNPs had a blood circulation half-life of about 2 hours. The transfected T cells were preferentially localized in tumors and tumor-draining lymph nodes, with a rapid RNA release profile	93
mRNAmCherry	Anti-CD3 antibody	LNP	Thiol-maleimide chemistry (DSPE-PEG5000-Mal)		0.13	∼−9	Jurkat T-cell leukemia cells		93
siRNA CKAP5	Anti-CD38 antibody	Ionizable LNPs	Thiol-maleimide chemistry	Ionizable cationic lipids (lipid 10), PEG-DMG, DSPC, and cholesterol	56–73	−1.7 to −6.4	Human CAG cell line	In vitro, the LNPs induced cell death of 90% of multiple myeloma cells. In vivo, 59.4% of multiple myeloma cells in the bone marrow took up siRNA within the first 4 hours, with sustained RNA release for 24 hours	94
siRNA CKAP5	Anti-CD38 antibody	Ionizable LNPs	Thiol-maleimide chemistry		0.05–0.11	−1.7 to −6.4	Human CAG cell line		94
siRNA XBP1	Anti-EGFR antibody	PLGA LNP	Thiol-maleimide chemistry (DSPE-PEG2000-Mal)	DOTAP and DSPE-PEG2000-Mal	∼230	∼−3	MDA-MB-231 and MCF-7 cell lines	The NPs significantly enhanced cellular uptake in TNBC cells, showing a 1.45-fold increase in fluorescence after 2 hours compared to non-targeted NPs. They achieved 75% XBP1 gene knockdown and enhanced apoptosis	95
siRNA XBP1	Anti-EGFR antibody	PLGA LNP	Thiol-maleimide chemistry (DSPE-PEG2000-Mal)	DOTAP and DSPE-PEG2000-Mal	∼0.3	∼−3	MDA-MB-231 and MCF-7 cell lines		95
siRNA PLK1	BsAb for PEG and EGFR	PEGylated LNP	Non-covalent complexation with PEGylated LNPs	DLin-MC3-DMA, cholesterol, DSPC, and varying PEG-lipids (DMG-PEG, DSG-PEG, DSPE-PEG)	64.8–79.5	−16.2 to −18.7	SH-SY5Y, SK-N-BE(2), and CHP-134 human neuroblastoma cell lines	They achieved significant PLK1 gene silencing by more than 2-fold and improved cell targeting by 1.2 to over 4.5 times. In vivo, tumor uptake was average 3 times higher than controls and persisted up to 48 hours, suggesting an acceptable circulation half-life	96
siRNA PLK1	BsAb for PEG and EGFR	PEGylated LNP	Non-covalent complexation with PEGylated LNPs		<0.3	−16.2 to −18.7			96