Targeted Nanoparticles That Deliver a Sustained, Specific Release of Paclitaxel to Irradiated Tumors

Abstract

To capitalize on the response of tumor cells to XRT, we developed a controlled-release nanoparticle drug delivery system using a targeting peptide that recognizes a radiation-induced cell surface receptor. Phage display biopanning identified Gly-Ile-Arg-Leu-Arg-Gly (GIRLRG) as a peptide that selectively recognizes tumors responding to XRT. Membrane protein extracts of irradiated glioma cells identified glucose-regulated protein GRP78 as the receptor target for GIRLRG. Antibodies to GRP78 blocked the binding of GIRLRG in vitro and in vivo. Conjugation of GIRLRG to a sustained-release nanoparticle drug delivery system yielded increased paclitaxel concentration and apoptosis in irradiated breast carcinomas for up to 3 weeks. Compared with controls, a single administration of the GIRLRG-targeted nanoparticle drug delivery system to irradiated tumors delayed the in vivo tumor tripling time by 55 days (P = 0.0001) in MDA-MB-231 and 12 days in GL261 (P < 0.005). This targeting agent combines a novel recombinant peptide with a paclitaxel-encapsulating nanoparticle that specifically targets irradiated tumors, increasing apoptosis and tumor growth delay in a manner superior to known chemotherapy approaches. Cancer Res; 70(11); 4550-9. ©2010 AACR.

Inhibition of C6 glioma in vivo by combination chemotherapy of implantation of polymer wafer and intracarotid perfusion of transferrin-decorated nanoparticles

“…Following the NPs arrival at the disease site in the body, the polymer matrix slowly degrades resulting in sustained release of the encapsulated therapeutic agents. Thus, the NPs have a dual capacity of drug targeting delivery and sustained release capability (28,29).…”

Supramolecular nanoscale assemblies for cancer diagnosis and therapy

“…Additionally new approaches based in fluorescent labelled DDS are used for identification of dysplasia by molecular imaging [49]. The prof-of-principle of targeting and drug release is being investigated by attaching antibodies to DDS [50] and by applying radiation [51,52] or by thermal effects in the tissues [53,54]. Nanosystems like dendrimers, liposomes, niosomes, metal based NPs, micelles, nanoemulsions, quantum dots and polymer NPs have been developed (Table 2).…”

Glutathione-triggered disassembly of isothermally responsive polymer nanoparticles obtained by nanoprecipitation of hydrophilic polymers

“…When functionalised with a targeting peptide these particles were used successfully to deliver paclitaxel to tumours exposed to 35 ionising radiation. 10 Yang et al reported the use of polyester/DNA nanoparticles to deliver the gene for vascular endothelial growth factor into stem cells to promote limb growth in mice, 11 and Palamoor and Jablonski exploited the gradual degradation of poly(orthoesters) for ocular applications, 40 achieving delivery of epinephrine over a period of several months. 12 Perhaps the most appealing feature of polyesters is for sustained (slow) release applications.…”

“…The principal aim of this study was to evaluate whether the nanoparticles would specifically disassemble in response to intracellular levels of GSH via reduction of the PDS solubility release catch. To verify a GSH-induced physical response, the 10 nanoparticles were held at 50 °C, GSH was added at 10 μM (extracellular) or 1 mM (intracellular) and the particle size measured. Addition of 10 µM GSH showed no changes visually, or by DLS.…”