Dual Functional Peptide-Driven Nanoparticles for Highly Efficient Glioma-Targeting and Drug Codelivery

Abstract

Compared with peripheral tumors, glioma is very difficult to treat, not only because it has general features of tumor but also because the therapy has been restricted by the brain-blood barrier (BBB). The two main features of tumor growth are angiogenesis and proliferation of tumor cells. RNA interference (RNAi) can downregulate VEGF overexpression to inhibit tumor neovascularization. Meanwhile, doxorubicin (DOX) has been used for cytotoxic chemotherapy to kill tumor cells. Thus, combining RNAi and chemotherapy has been regarded as a potential strategy for cancer treatment. However, the BBB limits the shVEGF-DOX codelivery system to direct into glioma. Here, a smart drug delivery system modified with a dual functional peptide was established, which could target to transferrin receptor (TfR) overexpressing on both the BBB and glioma. It showed that the dual-targeting delivery system had high tumor targeting efficiency in vitro and in vivo.

Noncovalent Strategy with Cell-Penetrating Peptides to Facilitate the Brain Delivery of Insulin through the Blood–Brain Barrier

“…47) The effect of D-R8 administered as a noncovalent form in the physical mixture was significantly meaningful, since the conventional methods that use specific ligands such as transferrin and Angiopep-2 usually require covalent linkage to drugs. 13,15,[19][20][21] Only one study suggested that synthetic carrier peptide combining sixteen lysine residues and low-density lipoprotein receptorbinding sequence (K16ApoE) had the potential to deliver the immunoglobulins to brain via noncovalent manner. 48) However, the delivery of immunoglobulins into the brain as well as other organs was achieved by larger carrier peptide with total 36 amino acids, and its finding was obtained by the semi-quantitative analysis without cytotoxicity examination; therefore, this cannot exclude the toxic possibility of K16ApoE peptide to the endothelial membranes.…”

“…For instance, receptor-mediated transcytosis has been used as one of the typical strategies. [13][14][15][16][17][18][19][20][21] However, this method requires covalent conjugation of the drugs with ligands for transferrin receptor and low density lipoprotein-related protein-1 (LRP1), requiring complicated preparation procedures and therefore raising concerns on the loss of therapeutic activity because of structural modifications. Another typical strategy that uses tight junction opening agents might be linked to the nonspecific influx of undesirable pathogens.…”

Everything You Always Wanted to Know about Poly‐l‐lysine Dendrigrafts (But Were Afraid to Ask)

“…[42] Another level of sophistication can be added to the formern anoparticle approach by replacing the targeting ligand by an activatable cell-penetrating peptide that is dual-triggered by the pH and MMP-2. Using the previously described vector G3-PEG-HAIYPRH, it has been shown that Dox as ac hemotherapeutic drug to kill tumour cells, and anti-VEGF (i.e.,v ascular endothelial growth factor) as ag ene to inhibit tumour angiogenesis, both synergically promoted ar emarkable extend of median survival time in treated glioma-bearing mice (i.e.,t wice as long in comparison untreated animals).…”

“…Using the previously described vector G3-PEG-HAIYPRH, it has been shown that Dox as ac hemotherapeutic drug to kill tumour cells, and anti-VEGF (i.e.,v ascular endothelial growth factor) as ag ene to inhibit tumour angiogenesis, both synergically promoted ar emarkable extend of median survival time in treated glioma-bearing mice (i.e.,t wice as long in comparison untreated animals). [42] Another level of sophistication can be added to the formern anoparticle approach by replacing the targeting ligand by an activatable cell-penetrating peptide that is dual-triggered by the pH and MMP-2. [43] The resulting nanotherapeutics displayed as uperior efficiency againstg lioma as ar esult of both tumour targeting andi nternalization functions.…”

New Potential In Situ Anticancer Agent Derived from [188Re]rhenium Nitro-Imidazole Ligand Loaded 5th Generation Poly-L-Lysine Dendrimer for Treatment of Transplanted Human Liver Carcinoma in Nude Mice

“…This method has at least three advantages as a powerful therapeutic tool: a) A spherical polycationic supramolecule dendrimer vector whose diameter is adaptable to embolize neo-vascularization of tumor stroma. In addition, the dendrimer injected directly into or near the tumor, remains in the site of injection and then could be considered as nano delivery system [36,37]; b) [ 188 Re]Rhenium, an isotope with a 16.9 h half-life, has a maximum beta energy compared to that of [ 90 Y]Yttrium and gamma emission of 155-KeV (15%) photon that is suitable for imaging [38]. This β emitter complexed with a nitro-imidazole ligand vector that is preferentially taken up by the hypoxic cells, resulting in the radiotoxic effect optimization [39]; c) Providing new targeting anticancer agents in situ for treating primary and/or metastatic tumors [35].…”