Retargeting nanoparticle albumin-paclitaxel to radiation-inducible receptors.

Abstract

e13560 Background: Ionizing radiation induces physiologic changes in cancer that uniquely alters cell surface molecules. Phage displayed peptide libraries were used to discover peptides that bind specifically to irradiated cancers. Methods: The amino acid sequence HVGGSSV achieved tumor-specific binding when conjugated to nanoparticles containing radiation sensitizing paclitaxel. Results: Near-infrared images showed binding in irradiated tumors treated with HVGGSSV-nab-paclitaxel, whereas tumors treated with SGVSGHV-nab-paclitaxel or nab-paclitaxel alone showed minimal radiance. Untreated (0 Gy) control tumors showed similar levels of radiance across all treatment groups. Irradiated tumors treated with HVGGSSV-nab-paclitaxel showed greater tumor specificity than SGVSGHV-nab-paclitaxel, or nab-paclitaxel (p<0.05). Radiation-guided delivery of nanoparticles improved both bioavailability of drug delivery and efficacy of radiotherapy in mouse models of lung cancer. Therapeutic efficacy of HVGGSSV guided nab-paclitaxel was studied in LLC and H460 lung carcinomas. On day 7 after tumor implantation, mice were injected with 10 mg/kg of either HVGGSSV-nab-paclitaxel, SGVSGHV-nab-paclitaxel, or nab-paclitaxel. Tumor volumes for each treatment group were measured until they reached a 4-fold increase in volume. Radiation alone achieved only a slight tumor growth delay (2 days) in LLC tumors, and 6 days in H460 tumors as compared to untreated controls. SGVSGHV-nab-paclitaxel controls showed no significant growth delay in LLC tumors and only 2 days delay in H460. After subsequent irradiation, this was improved to 2 days (LLC) and 6 days (H460). Treatment with nab-paclitaxel alone produced tumor growth delay of 2 days (LLC) and 6 days (H460), and upon additional irradiation increased to 6 days (LLC) and 11 days (H460). Both LLC and H460 lung carcinoma showed significant tumor growth delay for HVGGSSV-nab-paclitaxel as compared to nab-paclitaxel, SGVSGHV-nab-paclitaxel and saline controls. HVGGSSV-nab-paclitaxel treatment achieved a growth delay of 10 days (LLC) and 15 days (H460) over untreated controls. Conclusions: Thus, radiation can be used to guide nanoparticles to cancer. No significant financial relationships to disclose.