VEGF- and VEGFR2-Targeted Liposomes for Cisplatin Delivery to Glioma Cells

Abstract

Targeted delivery of anticancer drugs to brain tumors, especially glioblastoma multiforme, which is the most frequent and aggressive type, is one of the important objectives in nanomedicine. Vascular endothelial growth factor (VEGF) and its receptor type II (VEGFR2) are promising targets because they are overexpressed by not only core tumor cells but also by migrated glioma cells, which are responsible for resistance and rapid progression of brain tumors. The purpose of the present study was to develop the liposomal drug delivery system combining enhanced loading capacity of cisplatin and high binding affinity to glioma cells. This was achieved by using of highly soluble cisplatin analogue, cis-diamminedinitratoplatinum(II), and antibodies against the native form of VEGF or VEGFR2 conjugated to liposome surface. The developed drug delivery system revealed sustained drug release profile, high affinity to antigens, and increased uptake by glioma C6 and U-87 MG cells. Pharmacokinetic study on glioma C6-bearing rats revealed prolonged blood circulation time of the liposomal formulation. The above features enabled the present drug delivery system to overcome both poor pharmacokinetics typical for platinum formulations and low loading capacity typical for conventional liposomal cisplatin formulations.

Tumor Microenvironment Targeted Nanotherapy

“…In another study, siRNA- and DTX-loaded two receptor-specific peptides-modified liposomes [i.e., LDL receptor-related protein receptor (Angiopep-2) and neuropilin-1 receptor (tLyP-1)] were found to be having superior brain tumor targeting and tumor penetration (Yang et al, 2014 ). Shein et al ( 2016 ) focused on studying the effect of VEGF- and VEGFR2-targeted liposomes for delivery of cisplatin to C6 and U-87 MG glioma cells. The drug and antibody-conjugated liposomes exhibited prolonged release in vivo , superior affinity to antigens and enhanced uptake by the glioma cell lines.…”

Targeted co-delivery of protein and drug to a tumor in vivo by sophisticated RGD-modified lipid-calcium carbonate nanoparticles

“…For example, a membrane-associated cytokine TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) was attached outside of doxorubicin-loaded graphene nanoparticles [8]. Monoclonal antibodies are widely used in such combinations as both therapeutic units and targeting moieties by conjugation to the nanoparticles [9,10]. However, single carrier nanoparticles encapsulating a drug/protein combination where both components function in the cytosol has been rarely reported to date, while there are several examples of sequential treatments including apoptin proteins/dacarbazine [11], apoptin proteins/paclitaxel/etoposide [12], and caspase-3/flavopiridol [13] combinations.…”

Multicompartment Polymeric Nanocarriers for Biomedical Applications

“…[6,57] These multicompartment systems are of interest as they combine physicochemical properties of both liposomes and polymer capsules while minimizing some limitations associated with each system. Liposomes are natural lipid carriers which have potential to encapsulate a variety of small therapeutic cargoes including enzymes, [58] nucleic acids, [59,60] anticancer drugs, [61][62][63] proteins, [64,65] and imaging agents. [66,67] However, they can be prone to leakage.…”