Multifunctional PLGA nanocomposites to improve beta cell replacement therapy in Type 1 diabetes†

Abstract

Diabetes Mellitus is a rapidly growing global health problem, with its prevalence having risen sharply in recent years. Type 1 diabetes (T1D) treatment options are limited, with most of them significantly compromising the quality of life of these patients. This study presents the development and characterization of a multifunctional hybrid nanoformulation (mHNFs) designed to enhance the efficacy of beta cell replacement therapy in T1D. By encapsulating rapamycin and two types of magnetic nanoparticles (MnO and Fe₃O₄) within PLGA, we aimed to address critical challenges in islet transplantation, including hypoxia and immunosuppression. The synthesized nanoparticles demonstrated dual imaging capabilities as MRI contrast agents, sustained drug release, and in situ oxygen generation, crucial for mitigating islet hypoxia and loss of function. In vitro studies confirmed the cytocompatibility of the system and its efficient internalization by rin-m cells. Additionally, O₂ generation studies proved that mHNFs significantly reduced hypoxia levels. These results highlight the potential of these nanocarriers to improve the safety and efficacy of T1D islet transplantation treatments through a multifunctional approach.