Table 2.

Summary of All Investigations for Treatment of Glioblastoma with PAMAM Dendrimer Technology - Transfection of GB Cells and/Or Penetration of GB Tumor with Dendrimer

Investigators	Cytotoxic Cargo	Cell Lines	Results	Cell Viability Measurement	Distribution Analyses
Bae et al (2019)60	Apoptin	GBL-14	PAMAM-FHR showed improved apoptin gene transfection efficacy vs PAMAM alone. PAMAM-FHR/pJDK-apoptin complex demonstrated apoptosis induction in the GBL-14 cell line with minimal cytotoxicity in control dermal fibroblasts.	[In vitro] EZ-Cytox assay	N/A
Qiu et al (2018)62	B-cell lymphoma/leukemia-2 (Bcl-2) siRNA VEGF siRNA	U87MG	Bcl-2 and VEGF-siRNA delivery with Au DENPs-β-CD modified G5 dendrimers had high uptake of vector polyplex and gene product silencing capabilities and low cell cytotoxicity.	[In vitro] MTT assay	[In vitro] flow cytometry
Liu et al (2018)87	KLAK	U87MG	KLAK-TAT-PEG conjugated G4 dendrimers (PKT-S-PEG) demonstrated enhanced U87MG cytotoxicity via mitochondrial apoptosis as well as increased depth of tumor penetration in U87MG spheroids.	[In vitro] JC-1 assay	N/A
Stenstrӧm et al (2018)65	p42-MAPK siRNA	U87MG C6	G2, G3, and G4 dendrimers successfully complexed the siRNA. G3 and G4 dendrimers showed toxicity in primary neurons only at high concentrations and G2 showed none. G3 and G4 dendrimers were taken up in C6 cell line for p42-MAPK siRNA delivery.	[In vitro] LDH release	[In vitro] Rhodamine fluorescence microscopy
Uram et al (2017)63	Biotin Pyridoxal	U-118 SCC-15	Increased cellular uptake of biotinylated G3 PAMAM dendrimers for up to 24 hrs of incubation. Cell viability of U-118-MG cells reduced with high sensitivity using biotinylated G3 PAMAM dendrimers with lower normal cell cytotoxicity.	[In vitro] neutral red lysosomal stability assay & XTT assay	[In vitro] FITC confocal microscopy
Jiang et al (2016)75	Pep-1 (glioma homing peptides)	U87MG	PEGylated PAMAM dendrimers conjugated with glioma homing peptide (Pep-1) for targeting U87MG cells in vitro and U87MG tumor-bearing mice in vivo. Pep-1 conjugated dendrimers were not cytotoxic to U87MG cells in vitro but was localized within U87MG cell lysosomes. Dendrimer construct accumulated in the tumor within tumor-bearing mice.	[In vitro] MTT assay	[In vitro] FITC fluorescence microscopy [In vivo] FITC & Cy5.5 fluorescence microscopy
Zhang et al (2015)74	Fibrin-binding peptide CREKA	9L	G4 PAMAM dendrimers delivered intracranially for rodent gliosarcoma. Dendrimers distributed throughout tumor within 15 mins with high permeation and perfusion. Dendrimers cleared at a rate of 0.01 μg/g/hr and accumulated in the renal cortex.	N/A	[In vivo] FITC & Cy5.5 fluorescence
Zhao et al (2015)76	Fibrin-binding CREKA	U87MG	CREKA-conjugated PEGlyated PAMAM dendrimers enhanced fibrin binding capacity of dendrimers and increases uptake into glioma. Nanoparticles also found in kidney, liver, and spleen.	N/A	[In vitro], [In vivo], & [ex vivo] IVIS spectrum imaging
Yang et al (2014)88	Epirubicin Let-7g miRNA	U87MG	PAMAM dendrimers conjugated with Gd-NGO carried epirubicin and Let-7g miRNA which inhibited cancer cell growth and showed efficient transfection.	[In vivo] FAM-labelled fluorescence microscopy	[In vivo] FAM -labelled fluorescence microscopy
Yan et al (2011)54	Tumor vasculature targeted cyclic peptides BBB-permeable angiopep-2 peptides	U87MG	G5 PAMAM dendrimers packaged with peptides target integrin on tumor vasculature and LRP receptors on vascular endothelial cells and tumor cells for targeting U87MG GB cells.	[In vitro] MTT assay	[In vitro] & [In vivo] Den-RGD-Angio fluorescence microscopy
Ofek et al (2010)56	Luciferase siRNA	U87MG	PEI-PAMAM dendrimers delivered luciferase siRNA to silence luciferase gene expression in U87MG cancer cells with high efficacy and low cytotoxicity.	[In vitro] XTT assay	[In vivo] Bioluminescence imaging with mCherry and FITC-labelled luciferase siRNA