Moreover, aptamers are able to bind to nucleic acid, proteins, and small organic compounds and enable targeting to specific cells, in a manner similar to the concept of high-affinity antibodies. For example, a targeting nanoparticle was developed that had a mucin-1- (MUC-1-) specific Aptamer (Apt-NP) conjugated to the surface (Figure 9(b)). MUC1 protein is an attractive target for antiCAL101 cancer drug delivery owing to its overexpression in most Inhibitors,research,lifescience,medical adenocarcinomas. In this study, a reported MUC1 protein aptamer was exploited to target Paclitaxel- (PTX-) loaded PLGA NPs of ~225.3nm in size. Using MCF-7
breast cancer cells as a MUC1-overexpressing model, the aptamer increased the uptake of nanoparticles into the target cells as measured by flow cytometry. Moreover, the PTX-loaded Apt-NPs enhanced in vitro drug delivery and cytotoxicity to MUC1+ cancer cells, as compared with nontargeted NP lacking the MUC1 aptamer. The behavior of this novel aptamer-NP bioconjugate suggests that MUC1 aptamers may have Inhibitors,research,lifescience,medical a wider application potential in targeted gene delivery towards MUC1-overexpressing tumors . Other aptamers used for targeted delivery of NP have included PLGA conjugated to polyethylene
glycol (PEG), which have been used to deliver encapsulated prodrugs. PLGA NP are targeted using aptamers Inhibitors,research,lifescience,medical with affinity for the extracellular domain of PSMA [67, 68]. Such NP are highly efficacious compared to prodrugs in vivo, and pharmacokinetic studies showed improvements in tolerability and efficacy compared to standard chemotherapy (Figure 10). We envision that such a NP design might greatly enhance gene delivery targeted specifically to prostate cancer cells
expressing Inhibitors,research,lifescience,medical PSMA. Figure 10 Future Potential of PLGA-based nanoparticles for realizing efficient in vivo drug delivery. (a) PLGA formulations Inhibitors,research,lifescience,medical for drug delivery. The antitumor efficacy of single intratumoral injections of drugs or controls was compared for several NP groups. Groups … Other uses of aptamers have included a PLGA NP of ~156nm decorated with aptamer AS1411 (Apt-NP) . AS1411 is a DNA aptamer that specifically binds to nucleolin, a protein upregulated in the plasmsa membrane of both cancer cells and angiogenic blood vessels. Apt-NP was used to facilitate antiglioma delivery of paclitaxel (PTX). The Ap-nucleolin interaction significantly enhanced cellular association of nanoparticles in C6 glioma cells and increased the cytotoxicity of many its payload. Prolonged circulation and enhanced PTX accumulation at the tumor site were achieved by Ap-PTX-NP, which also yielded higher tumor inhibition on C6 glioma xenografts and prolonged survival when comapred to PTX-NP (untargeted) and Taxol. Therefore, aptamer-functionalized PLGA NP can be an efficient therapeutic and this design might be adapted as well for successful potential gene delivery to glioma. Antibodies.