Abstract 4472: Targeted multifunctional lipid-PLGA hybrid nanosystems for metastatic breast cancer imaging and therapy

Abstract

Abstract Introduction: Targeted theranostic nanoparticles based on near-infrared fluorescence is a novel concept in next-generation medicine that combines diagnostics and therapeutics simultaneously to radically change the way we diagnose, image and treat the breast cancer. Often these targeted therapies are efficacious and at the same time less toxic than traditional regimens. Our aim is to formulate a multifunctional theranostic agent capable of tumor targeting and tumor imaging along with anticancer therapy for metastatic breast cancer. Methods: We engineered lipo-polymeric composite multifunctional nanoparticles co-encapsulated with long lived dyes (like ADOTA) together with a combination of anticancer drugs, docetaxel and curcumin by nanoprecipitation. These anticancer agents have been found to show synergistic anti-angiogenic effects. Further, curcumin has the potential to downregulate P-glycoprotein expression which helps in reversing drug resistance seen with drugs like docetaxel, thereby potentiating the activity of the drug at lower concentrations. The formulated composite nanoparticles are conjugated to Annexin A2 (AnxA2) peptide (LCKLSL) to enable specific targeting to tumor site. LCKLSL hexapeptide in the amino-terminal domain of the AnxA2motif is essential for tissue plasminogen activator binding. Therefore AnxA2 peptide will serve as a useful therapeutic target against invasion and metastasis. Results: Multifunctional nanoparticles were successfully formulated and then characterized for drug loading efficiency, particle size, encapsulation efficiency, surface morphology, zeta potential and in vitro drug release profiles. The results show smooth and spherical nanoparticles when seen under TEM with drug encapsulation of 50% for curcumin and 19% for docetaxel. The particle size distribution showed uniform distribution with average size being110±10nm. Zeta potential varied between -35±5mV. Percent AnxA2 peptide attachment on the nanoparticles was determined by using Flow cytometry and found to be 74%. Intracellular uptake in breast cancer cell line (MDA MB231) was carried out and showed robust uptake. The nanoparticle formulations were further evaluated by cytotoxic studies and synergy between anticancer drugs was established. Mouse xenograft studies showed significant tumor regreesion for AnxA2 targeted curcumin and docetaxel loaded hybrid nanoparticles as compared to untreated mice. Conclusion: This study would help validate these targeted theranostic nanoparticles in metastatic breast cancer mouse model thus highlighting the immense clinical potential of targeted multifunctional theranostic nanoparticles for imaging and therapy of metastatic breast cancer. Note: This abstract was not presented at the meeting. Citation Format: Amalendu P. Ranjan, Anindita Mukerjee, Jamboor K. Vishwanatha. Targeted multifunctional lipid-PLGA hybrid nanosystems for metastatic breast cancer imaging and therapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4472. doi:10.1158/1538-7445.AM2014-4472