Dual‐Targeting Heparin‐Based Nanoparticles that Re‐Assemble in Blood for Glioma Therapy through Both Anti‐Proliferation and Anti‐Angiogenesis

Abstract

The efficient and specific delivery of nanoparticles (NPs) to brain tumors is crucial for successful glioma treatment. Heparin‐based polymers decorated with two peptides self‐assemble into multi‐functional NPs that specifically target glioma cells. These NPs re‐self‐assemble to a smaller size in blood, which is beneficial for in‐vivo brain drug delivery. The hydrodynamic size of one type of these NPs is 63 ± 11 nm under blood‐mimic conditions (10% fetal bovine serum), but it is 164 ± 16 nm in water. Additionally their zeta potential is more neutral in the blood‐mimic conditions. Transmission electron microscopy reveals the morphology of the spherical NPs. In vitro experiments demonstrate that the NPs exhibit a high cellular uptake and the ability to efficiently discourage proliferation, endothelial‐lined vessels, and vasculogenic mimicry. In vivo studies demonstrate that the NPs can by‐pass the normal blood–brain and blood–(brain tumor) barriers and specifically accumulate in glioma tissues; moreover, they present an excellent anti‐glioma effect in subcutaneous/intracranial glioma‐bearing mice. Their superiority is due to their appropriate size in blood and the synergic effect arising from their targeting of two different receptors. The data suggests that these NPs are ideal for anti‐glioma therapy.

Antiangiogenic Targets for Glioblastoma Therapy from a Pre-Clinical Approach, Using Nanoformulations

“…Of the 24 articles identified in the Cochrane Library, no articles were included, as 16 articles were reviews, 5 were protocols, and 3 were clinical articles in the screening analysis. In total, only 27 full-text articles not duplicated were included in this systematic review [ 32 , 34 , 38 , 41 , 43 , 44 , 45 , 48 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 ], as illustrated in Figure 1 .…”

Nanotherapeutics engineered to cross the blood-brain barrier for advanced drug delivery to the central nervous system

“…However, all models used in these studies are either brain injury or brain tumor models, where the BBB structure is often disrupted. On the other hand, targeting ligands are attached on the surface of nanoparticles in order to deliver those across the healthy or intact BBB, including cRGD [56,57], PS-80 [58], transferrin [59], IgG [60], and Pep-1 [61]. Electrostatic interaction-based entangled polymer nanoparticles designed to deliver therapeutic molecules across the BBB used a nanocomplex that has a cationic polymer network, polyethyleneimine (PEI) and poly-L-lysine (PLL) with plasmid DNA [62].…”

A rational design of a cancer-specific and lysosome-targeted fluorescence nanoprobe for glutathione imaging in living cells

“…[39][40][41][42][43][44][45][46] Up to now, several polymeric nanoparticle-based dual-targeting nanoprobes have been developed for cancer imaging and therapy. [47][48][49][50][51][52][53][54] However, to the best of our knowledge, dualtargeting fluorescence polymeric nanoprobes for efficiently detecting lysosomal GSH within specific cancer cells have not yet been reported.…”