Table 2.

Examples of potential nano-delivery systems for various phytochemicals in the treatment of GBM

Phytochemical	Nano delivery system	Properties	References
Curcumin	Anti-EGFRvIII-PLGA	Biocompatible, biodegradable, and versatile with high specificity towards EGFRvIII overexpressing cells	[79, 82, 84]
	PLGA-DSPE-mPEG	Narrow particle size distribution and provides prolonged curcumin release (168 h)	[82]
	m-PNPs	Controlled curcumin release and can be conjugated with GRGDS for enhanced bioavailability of curcumin	[84]
	mPEG-PCL	High drug encapsulation efficiency, high drug loading content, slow curcumin release (120 h for sustained drug exposure, with approximately 20% burst from the NP surface within the first 10 h	[86]
	Micellar NPs	Low bioavailability of curcumin in tumor and high serum curcumin concentrations	[89]
	ZpD-G23 NPs	Biocompatible, biodegradable, stable with an increased hydrophilicity, reactivity and ability to circulate and, can cross the BBB via trans endocytosis	[85]
	Chitosan coated mesoporous silica NPs	Nontoxic, biocompatible, and biodegradable. Chitosan coating is pH sensitive, making it suitable for controlled drug delivery	[112]
	Niosome NPs	Safe, biocompatible, biodegradable, non-immunogenic, able to cross the BBB with high curcumin encapsulation efficiency and release drugs in a sustained manner	[87]
	PBAE (poly(beta-amino ester)	Highly selective and suitable for the delivery of drugs in a steady, controlled manner	[113]
Luteolin	mPEG-PCL	Stable, biodegradable, soluble in aqueous solution, improves drug bioavailability, retention at tumor site and selectivity	[92]
	Fa-PEG-PCL	Slow drug release to maintain the desirable drug concentration at tumor region. Smaller diameter to facilitate active diffusion through tumor cell intercellular junctions	[91]
Quercetin	Dextran coated SPIONs	Less toxic, suitable for targeted drug delivery systems due to their magnetic properties, increased quercetin bioavailability in brain. Biodistribution of quercetin can be regulated with the aid of an external magnet	[94]
	PMMs	Stable for over 60 days, have a high encapsulation capacity, release quercetin in a sustained manner and have an enhanced safety and efficacy	[95]
	PLGA NPs	High cellular uptake, small in size and improves solubility and bioavailability of quercetin	[96]
	Freeze-dried Polymeric micelles	Released quercetin in a sustained drug release pattern, increased the concentration of quercetin at primary tumor tissues and its cellular uptake	[97]
Resveratrol	Pep-PP	Highly selective for IL-13Rα2 overexpressing GBM cells, specific and enhances the intracellular retention of resveratrol	[98]
	mPEG-PCL	Encapsulation efficiency of over 90% and a sustained drug release	[99]
	Tf-PEG-Lip	Selective for transferrin overexpressing tumor cells, able to cross the BBB, stable, easily scalable, have a sustained drug release pattern and a good drug loading capacity	[101]
	Tf-PEG-PLA	Cross the brain through Tf mediated transcytosis, increases resveratrol’s cellular uptake and have less toxicity	[102]
	SPIONs-CPTES	Small in size, high surface to volume ratio, high magnetic moment, biocompatible and surface coating consisting of HAPtS and CPTES enhances passage via the BBB barrier	[103]
	SLNPs	Small sized, biodegradable, biocompatible, able to cross the BBB, released resveratrol in a sustained drug release pattern and enhanced resveratrol’s brain concentration	[104]
Asiasic acid	PCL	Sustained drug release pattern and effective at low half-maximal inhibitory concentration (IC50)	[105]
	MS-SLNPs	Small in size, high drug loading capacity and reduced toxicity	[106]
	Tf-PLGA	High selectivity, cellular intake, encapsulation efficiency and slow drug release	[107]
	RGD-SLNPs	High selectivity and penetration capacity in spheroid models	[108]
Gallic acid	GNPs	Small in size, biocompatible, low biotoxicity and easy to be synthesized	[109]
	Fe–GA/BSA	pH-responsiveness, good biocompatibility and low toxicity	[110]
	Dextran-coated MNPs	Enhanced stability, superparamagnetism and increased cellular internalization	[111]

EGFRvIII, Epidermal growth factor receptor variant III; PLGA, Poly (D, l-lactic-co-glycolic acid); DSPE-mPEG, 1,2-Distearoyl-glycerol-3-phospho-ethanolamine-N-[methoxy (polyethylene glycol)-2000] ammonium salt; mPNPs, Magnetic polymeric nanoparticles; ZpD-G23, Dodecamer peptide-functionalized polydopamine-coated zein; PCL, Polycaprolactone; SPIONs, Superparamagnetic iron oxide nanoparticles; PMM, Polymeric mixed micelles; qNPs, Quercetin nanoparticles; Fa, Iron; Pep-PP, Pep 1-PEG-b-PCL; lip, Liposomes; Tf, Transferrin; CPTES, 3-Chloropropyltriethoxysilane; SLNPs, Solid lipid NPs; MS, Glyceryl monostereate; RGD, Arginyl-glycyl-aspartic acid; GNPs, Gold nanoparticles; GA/BSA, Gallic acid/bovine serum albumin; PLA, Poly lactic acid and MNPs, Magnetic nanoparticles