Surface engineered Fe3O4 nanomagnets for pH-responsive delivery of gemcitabine hydrochloride and in vivo tracking by radiolabeling

Abstract

Gemcitabine, a well-known nucleoside analogue, has shown tremendous potential against solid tumors. However, its clinical use is limited due to its poor biological half-life and low target to non-target ratio. In this regard, we have developed polyphosphate grafted Fe₃O₄ nanomagnets (PPNMs) for efficient delivery of gemcitabine hydrochloride (GEM). These nanocarriers are highly dispersible in physiological medium and possess sufficient surface charge (−25 mV) for electrostatic binding of positively charged GEM. The successful loading of GEM on PPNMs was evident from UV-visible absorption, FTIR spectroscopy and light scattering studies. The GEM loaded PPNMs (GEM-PPNMs) exhibited pH triggered release of the loaded drug, substantial cellular internalization, and higher toxicity towards human lung cancer (A549) and breast cancer (MCF-7) cell lines over pure drug. Further, the biodistribution of these nanocarriers was assessed by their tracking in a mouse model through radiolabeling with ⁶⁴Cu and ¹⁷⁷Lu. It has been observed that a radiolabeling yield of >90% can be achieved with PPNMs concentrations of 1 mg mL⁻¹ and 0.5 mg mL⁻¹ in 60 min for ⁶⁴Cu and ¹⁷⁷Lu, respectively, at room temperature. The radiolabeled PPNMs (⁶⁴Cu-PPNMs and ¹⁷⁷Lu-PPNMs) were highly stable during the study period in saline solution. Though the radiolabeled system exhibited higher uptake in the liver and spleen upon intravenous injection, a substantial uptake of the same was also found in the tumor. Specifically, the present study demonstrated the efficacy of PPNMs for delivery of GEM as well as their in vivo tracking by radiolabeling.