AS1411 aptamer tagged PLGA‐lecithin‐PEG nanoparticles for tumor cell targeting and drug delivery

Abstract

Liposomes and polymers are widely used drug carriers for controlled release since they offer many advantages like increased treatment effectiveness, reduced toxicity and are of biodegradable nature. In this work, anticancer drug-loaded PLGA-lecithin-PEG nanoparticles (NPs) were synthesized and were functionalized with AS1411 anti-nucleolin aptamers for site-specific targeting against tumor cells which over expresses nucleolin receptors. The particles were characterized by transmission electron microscope (TEM) and X-ray photoelectron spectroscopy (XPS). The drug-loading efficiency, encapsulation efficiency and in vitro drug release studies were conducted using UV spectroscopy. Cytotoxicity studies were carried out in two different cancer cell lines, MCF-7 and GI-1 cells and two different normal cells, L929 cells and HMEC cells. Confocal microscopy and flowcytometry confirmed the cellular uptake of particles and targeted drug delivery. The morphology analysis of the NPs proved that the particles were smooth and spherical in shape with a size ranging from 60 to 110 nm. Drug-loading studies indicated that under the same drug loading, the aptamer-targeted NPs show enhanced cancer killing effect compared to the corresponding non-targeted NPs. In addition, the PLGA-lecithin-PEG NPs exhibited high encapsulation efficiency and superior sustained drug release than the drug loaded in plain PLGA NPs. The results confirmed that AS1411 aptamer-PLGA-lecithin-PEG NPs are potential carrier candidates for differential targeted drug delivery.

Selective Delivery of PEGylated Compounds to Tumor Cells by Anti-PEG Hybrid Antibodies

“…Proteins, peptides containing specific motifs such as arginine-glycine-aspartic acid (RGD; ref. 33), folate (34), antibodies and antibody fragments (immunoliposomes), nucleic acids (35), and transferrin (36) have been conjugated to PEGylated nanoparticles to facilitate active targeting.…”

Concepts and practices used to develop functional PLGA-based nanoparticulate systems

“…AS1411 anti-nucleolin aptamers have also been conjugated to PEGylated lipid-PLGA hybrid nanoparticles containing paclitaxel to target tumor cells that overexpressed nucleolin receptors. 159 These functional lipid-PLGA hybrid nanoparticles displayed greater cytotoxic effects toward cancer cell lines such as MCF-7 cells than did the aptamer-free nanoparticles. Additional notable features were that this approach enabled better drug encapsulation efficiency and superior sustained drug release than was possible with bare paclitaxel-loaded PLGA nanoparticles.…”

Nanotechnology-based approaches in anticancer research

“…136 Anticancer drugs loaded in PLGA-lecithin-PEG NPs and functionalized with AS1411 antinucleolin aptamers have been reported as having high encapsulation efficiency and superior sustained drug release for differential targeted drug delivery in cancer treatment. 137 Aptamer-functionalized PEG-PLGA nanoparticles have been reported with enhanced delivery of paclitaxel as a therapeutic application in the treatment of gliomas. 138 Targeted delivery of an anticancer agent, cisplatin, against prostate cancer cells by aptamer-functionalized Pt(IV) prodrug-PLGA-PEG NPs have been also reported with higher efficiency compared with free cisplatin.…”