Table 3.

^{Antibody−conjugated nanospheres for brain cancer treatment}

Type of polymer used	Antibody conjugated + target receptor	Encapsulated Compound	Size	Surface charge	Outcomes (in vitro)	Outcomes (in vivo)	References
PMLA and PEG	Transferrin (TfR) antibody targeting transferrin receptor on brain cancer cells and vascular endothelium	TMZ (TMZ)	6.5 nm to 14.8 nm	-6.3 mV to -17.7 mV	-Lower potency on U87MG cells with nanoconjugates than with free TMZ	-Increase in the half-life of conjugated TMZ (about 3–4 times) compared with free TMZ -In U87MG cells (TfR-expressing), free TMZ was more potent than nanoconjugate. The most potent nanoconjugate was P/PEG(2%)/LLL(40%)/TMZH(17%)/HuTfR mAb. -In MDA-M8-468 cells, nanoconjugates were more effective at reducing cancer cell viability than free TMZ	[210]
PLA	Cetuximab inhibiting the PI3K pathway	Alpelisib and,1’-Dioctadecyl-3,3,3’,3’-tetramethylindocarbocyanine perchlorate (DiR) dye	100 nm	-	-Reduction in cell viability (73.8%) for antibody-conjugated nanoparticles compared with non-targeted nanoparticles (70.6%) when tested in SCC cell lines at 6 h -Improved cellular uptake by Cal33 cells with cetuximab-conjugated nanoparticle (more than 85% of cells after 6 h) than non-targeted nanoparticles, based on fluorescence studies	-Improved tumor targeting with antibody-conjugated nanoparticles than without	[211]
Chitosan grafted with PEG	Transferrin (TfR) (CD71) antibody conjugation targeting transferrin receptors on brain cancer cells	Dil fluorescent dye	284.1 nm	+ 34.4. mV	-Higher cytotoxicity in hCMEC/D3 cells with TfRmAB-conjugated nanoparticles (77.3% cell viability) than with non-targeted nanoparticles (92%) after 24 h incubation -Higher cellular uptake in hCMEC/D3 cells than non-targeted nanoparticle -Internalization of TfRmAb-conjugated nanoparticles inhibited by both amiloride and chlorpromazine (inhibition of macropinocytosis and transcytosis)		[212]
PLGA	Anti-EGFRvIII MAb targeting EGFR receptors on glioblastoma cell line (DKMG/EGFRvIII cells)	Curcumin	249 nm to 280 nm	-13.1 mV to -1.4 mV	-Cytotoxicity for nanoconjugates is dose-dependent -More significant cytotoxicity towards DKMG/EGFRvIII glioma cells with MAb-CUR-PLGA NPs compared with non-targeted nanoparticles (at 40 and 60 µM) -Higher internalization in DK-MGlow cells of MAb-CUR-PLGA NPs than non-targeted nanoparticles -No cytotoxicity effects seen in DKMG/EGFRvIII cells with CUR-PLGA NPs and MAb-CUR-PLGA NPs without irradiation		[213]
Poly (butyl cyanoacrylate) (PBCA) with PEGylation	Anti-endothelial growth factor receptor (anti-EGFR) antibodies targeting EGFR expressed in glioblastoma cells	Carboplatin	365 nm	-10.7 mV	-Higher stability of drug when encapsulated in antibody-conjugated nanoparticle	-Higher survival times (23.5 days) in rats that were administered antibody-conjugated nanoparticles -Lower cytotoxicity to other tissues for antibody-conjugated nanoparticle than free carboplatin (40% higher)	[214]
PMLA	Anti-mouse transferrin receptor antibody and anti-nucleosome antibody 2C5 targeting receptors on U87MG glioma cels	Polycefin variant	20 nm to 30 nm	-	-Higher cytotoxicity with antibody-conjugation than without -Highest U87MG cellular uptake of 2C5-conjugated nanoparticle after 1 h. No internalization without 2C5 antibody.	-Higher drug accumulation in cultured human glioma cells and tumors in nude mice with induced glioblastoma with dual-targeted nanoparticle compared with nanoparticles only conjugated with anti-TfR or 2C5 antibody	[174]
Chitosan-PLGA	Cetaxizumab (CTX) antibody targeting different glioma cell lines (U251 and SW1088)	alpha-cyano-4-hydroxycinnamic acid (CHC)	213 to 875 nm	+ 33.2to + 58.9 mV	-Insignificant cell viability reduction when CHC is encapsulated in LGA/OCS NP, compared with PLGA/TMC NP -Higher cytotoxicity towards U251 and SW1088 glioma cells with antibody-conjugated nanoparticles compared to control (about 5% cell viability) -Enhanced antiangiogenic activity of conjugated nanoparticles compared to those without		[215]
PLGA-PEG	Anti-EGFRvIII MAb targeting EGFR receptors on glioblastoma cell line (U87MG vIII cells)	DOX	196.5 nm	-5.05 mV	-Higher cellular uptake was shown by MAb-DXR-PLGA NP -Enhanced sustained drug release at pH 7.4 by MAb-DXR-PLGA nanoparticles compared to without -Higher cytotoxicity towards U87MG vIII cell line shown by MAb-DXR-PLGA NP compared with unconjugated nanoparticle antibody conjugation		[216]
PMLA	Anti-TfR mAb targeting Transferrin receptors on glioma cells (T98G and RG62 cells)	Antisense oligonucleotides (AONs)	2 nm	-5.2 mV	-Different nanoparticle composition affects membrane-disruptive ability (P/LLL was pH independent while P/LOEt nanoparticle was pH-independent) -Higher cytotoxicity with P/LOEt nanoconjugates at 0.15 mg/mL but higher concentrations (0.5 mg/mL) caused cell shrinkage. This was not seen with P/LLL nanoconjugates	-Higher tumor growth inhibition with LLL-nanoconjugate (about 2 times) than LOEt-nanoconjugate -No anti-tumor effect with nanoconjugates without AONs or anti-TfR mAbs -Reduction in brain vessel area with LOEt/AON/Hu/Ms and P/LLL/AON/Hu/Ms than in control group	[180]
PLGA	Anti-OX40 mAb to enhance cytotoxic T-cell (CD4 and CD8) response against glioma cells	Anti-OX40 mAb	86 nm	-12.8 mV	-Higher sustained release of anti-OX40 mAb compared to control -Increased cytotoxic activity of cytotoxic T-cells with anti-OX40-PLGA-NP -Higher CTL proliferation with anti-OX40-PLGA-NP compared with anti-OX40 mAb and untargeted nanoparticle -No significant difference in T-cell proliferation between anti-OX40-PLGA-NP and immobilized anti-OX40		[217]