Lotus pollen extract–regulated calcium carbonate hollow nanospheres as efficient mitochondria-targeted drug carriers

Abstract

The subcellular organelle-targeted delivery strategy appears to be an effective method to induce drug accumulation in the desired sites for enhanced therapeutic efficacy. However, insufficient lysosomal escape constitutes a major barrier to the efficient delivery of drugs to targeted tissues. Mitochondria-targeted drug delivery systems (DDSs) have emerged as a promising alternative and attract considerable research interest. However, sophisticated post-modification procedures are a prerequisite for acquiring the mitochondria-targeted feature, resulting in far too much complexity to achieve effective performance. Herein, mitochondria-targeted calcium carbonate hollow nanospheres were easily synthesized just by the regulation of lotus pollen extract. The biomolecules in lotus pollen extract not only regulate the morphology and structure of calcium carbonate, but also endow it with an excellent mitochondria-targeted property. The hollow calcium carbonate nanospheres exhibit remarkable capability for drug loading, and DOX loading entrapment was calculated to be 85.80%. The co-localization analysis of Pearson's correlation factor also proves the good lysosomal escape and mitochondria-targeted characteristics of this system. Furthermore, the drug in this mitochondria-targeted drug delivery system shows pH-dependent and sustained-release behavior at the tumor site, which significantly augments the apoptosis-inducing effect. This work may provide a helpful reference for the design and synthesis of subcellular organelle-targeted DDSs.