Selective trafficking of light chain-conjugated nanoparticles to the kidney and renal cell carcinoma
Farideh Ordikhani, Vivek Kasinath, Mayuko Uehara, Aram Akbarzadeh, Osman A. Yilmam, Li Dai, Hamza Aksu, Sungwook Jung, Liwei Jiang, Xiaofei Li, Jing Zhao, Baharak Bahmani, Takaharu Ichimura, Paolo Fiorina, Nasim Annabi, Reza Abdi
Abstract
Specific delivery platforms for drugs to the kidney and diagnostic agents to renal cell carcinoma (RCC) constitute urgent but unfulfilled clinical needs. To address these challenges, we engineered nanocarriers that interact selectively for the first time with proximal tubule epithelial cells (PTECs) in the kidney and with RCC through the interplay between lambda light chains (LCs) attached to PEGylated polylactic-co-glycolic acid (PLGA) nanoparticles and the membrane protein megalin. Systemic administration of these light chain-conjugated nanoparticles (LC-NPs) to mice resulted in their specific retention by megalin-expressing PTECs for seven days. Repetitive dosing of LC-NPs demonstrated no renal toxicity. LC-NPs also localized selectively to megalin-expressing RCC tumors in mice. Moreover, we confirmed that both the primary tumor and lymph node metastases of human RCC express megalin, reinforcing the potential of LC-NPs for clinical use. Thus, LC-NPs can contribute potentially to improving the management of both non-oncologic and oncologic renal disorders.