Table 2.

Antibody-conjugated dendrimers used for brain cancer treatment

Type of polymer used	Antibody-conjugated target receptor	Encapsulated Compound	Size	Surface charge	Outcomes (in vitro)	Outcomes (in vivo)	Reference
PAMAM dendrimer	Anti-EGFRvIIImAb (L8A4) and anti-EGFR mAb (cetuximab)	Boron-10	-	-	-L8A4 and cetuximab bind to different parts of the EGFRvIII molecule	-Higher drug accumulation at the tumor site for the dual-antibody-conjugated dendrimer (61.4% of the injected dose per gram) compared with L8A4 conjugation (30.8%) and C225 conjugation alone (34.7%) -Higher mean survival time in rats with F98 gliomas (55 days) compared to L8A4 (36 days) and C225 alone (38 days) -Poor delivery of boron for BNCT with C225 mAb in EGFRvIII- expressing gliomas	[197]
PAMAM dendrimer	CD133 monoclonal antibodies targeting CD133-positive glioma stem cells (GSCs)	Boron-10	-	-	-Higher cellular uptake for CD133-conjugated dendrimers in CD133 + GSCs (90%) compared with in CD133- cells (40%)	-Higher boron accumulation in CD133 + glioma xenografts compared with CD133- xenografts after administration of PD-CD133/BSH with minimal accumulation in other sites -No significant difference in boron levels between CD133 + and CD133- xenografts with combination therapy (PD-CD133/ BSH and BSH) due to loss of selective targeting -Higher mean survival times in mice with CD133 + implanted glioma xenografts (61.8 days) compared with mice implanted with CD133- glioma xenograft (46.7 days)	[172]
PAMAM dendrimer	Anti-EGFR mAb, cetuximab (C225) targeting EGFRvIII mutant receptor	Methotrexate	-	-	-Higher in vitro mean nanoparticle accumulation in mutant F98 glioma cells (62.9% ID/g tumor) compared with F98 wild-type cells (11.3%/g tumor)	-No significant difference in median survival times, with C255-conjugated nanoparticle, free mAb and free drug, in glioma-bearing mice	[198]
Polylysine G5 dendrimers	anti-programmed cell death ligand 1 (aPD-L1) monoclonal antibody targeting programmed-death ligand 1	Cy5	21.4 nm	+ 21.1 mV	-Higher tumor penetration with G5-R nanodots	-Higher survival times in mice with CT26 tumors when aPD-L1 conjugated G5-dendrimers  (> 50 days) compared with control groups (35 days)	[199]
Phosphorus dendrimer (AK128)	Anti-PD-L monoclonal antibody targeting programmed-death ligand 1	BSA	228.7 nm	-10.3mV	-Higher cellular uptake with dendrimer (2.2 times) than without dendrimers -No significant increase in NK cell proliferation with aPD1 or aPD1-conjugated dendrimer compared to AK128 alone -Highest BBB penetration efficacy with AK128-aPD1@M1m NCs compared with other groups -Higher levels of apoptosis of C6 cells when antibody-conjugated dendrimer was administered (31.7%) compared to control groups due to higher natural killer cell proliferation	-Dual targeting with M1m and aPD1 antibody allows enhanced recruitment of T lymphocytes and NK cells into glioma and spleen and increase in Tregs in tumor sites -Higher tumor inhibition efficacy with aPD1 conjugated dendrimer (11.02%) compared to control groups	[200]
Hyperbranched polymeric (HBP) nanoparticle (with PEGylation)	HER3 bispecific-antibody fragment, lumretuzumab, targeting HER3 receptor expressed in breast cancer brain metastasis	DOX	480 nm	-	-High targeting specificity of HER3-bsAb to HER3 receptors -Lower accumulation of HER3-HBPs in the brain than untargeted HBPs due to poorer BBB penetration as a result of larger molecular size	-No significant reduction in tumor growth with HER3-HBP-DOX group compared with untargeted group -More significant cytotoxicity for HER3-HBP than without antibody conjugation (14 times higher intracranial drug accumulation) with HER3-HBP than without antibody conjugation	[184]
Targeted Lyposome/activated nanoparticles (tLyp)	Anti-NKG2A monoclonal antibody targeting NK and T cells to stimulate immune response (also conjugated with cell penetrating peptides tLyp-1 to form tLyp/aNKNP-siRNA	siLSINCT5 (siRNA)	103.42 nm	6.81 mV	-More significant tumor growth inhibition with tLypNP-siRNA and tLyp/aNKNP-siRNA compared with non-targeted NP, but no significant difference seen between aNKNP-siRNA and NP-siRNA - Higher U87 cell apoptosis with tLyp/aNKNP-siRNA (38.94%) compared with control groups	-Higher U87 tumor growth inhibition with tLyp/aNKNP-siRNA than in control groups -Higher levels of NK and T cells with tLyp/aNKNP-siRNA than in control groups, as shown in immunofluorescence studies -Higher drug accumulation in brain tumor site with tLyp/aNKNP-siRNA compared to other groups 24 h post-injection, but this decreases 36 h after injection (metabolic activity)	[201]
G7-anti-programmed cell death ligand 1(G7-aPD-L1)	Anti PD-L1 immune checkpoint inhibitors		27.4 nm	-	-Significant increase in IL-2 production with G7-aPD-L1h conjugates (1.9 times higher) than untargeted nanoparticles -Higher cellular retention in cancer cells with G7-c conjugates than free aPD-L1h -Higher cytotoxicity with antibody conjugation than with untargeted nanoparticles, where no cytotoxic effect was observed	-Higher tumor accumulation of G7-aPD-L1 compared with non-targeted nanoparticle 72 h post-injection	[202]
PAMAM dendrimer-based polyplex containing plasmid DNA encoding the interferon-beta (PAMAM-R/pORF-IFN-β polyplex )	No antibody conjugated	human interferon beta (IFN-B) plasmid	-	-	-	-Higher tumor inhibition with PAMAM-R/pORF-IFN-β compared to without gene in mice with brain tumors -Higher tumor cell apoptosis and selectivity	[203]
Hyperbranched polyglycerol-conjugated poly(lactic-co-glycolic acid)- (OX26–HPG–PLGA)	Transferrin antibody (OX26), targeting transferrin receptors	Endomorphins (analgesic drug)	170 nm	-27 mV	-Uptake of nanoparticles into brain microvascular endothelial cells in a time- and concentration-dependent manner, with filipin enhancing uptake at the same NP concentration	-Stronger and earlier analgesic effect with OX26-conjugated nanoparticles compared with untargeted nanoparticles and free drug (higher uptake of nanoparticles into brain microvascular endothelial cells)	[166]