Multifaceted Pt Nanoclusters for Targeting Recognition, Cellular Uptake, and Therapy In Vivo and In Vitro in Chronic Myeloid Leukemia Cells

Abstract

In the past few years, platinum nanomaterials (Pt NMs) have gained attraction owing to their ability to address the drawbacks of classical Pt-based chemotherapy drugs including drug resistance and clinical side effects, which have been preliminarily used in lung cancer, liver cancer, gynecological cancer, etc. In order to investigate the effect of Pt NMs on hematopoietic tumors, ultra-small Pt nanoclusters (Pt NCs) were employed to clarify their targeting recognition, cellular uptake, and effective therapy in vivo for chronic myeloid leukemia (CML) cells. Through the facile surface modification of Pt NCs with anti-CD19 to form the anti-CD19-Pt NC composite, the specific aggregation in BV173 cells could be realized based on their high protein expression of CD19 in comparison to that in CD19-negative K562 cells. Furthermore, the endocytic pathways of Pt NCs in K562 and BV173 cells were investigated by qualitative and quantitative analyses via inductively coupled plasma-optical emission spectroscopy and flow cytometry. It was observed that Pt NCs entered into the K562 cells mainly through the caveolin-dependent endocytic pathway and in BV173 cells primarily via phagocytosis and micropinocytosis. Moreover, these Pt NCs exerted an excellent inhibitory effect on proliferation, migration, and invasion of hematopoietic tumor cells and tended to gather the acidic organelles (lysosomes or endosomes), resulting in the proliferation inhibition of tumor cells by the generation of corrosive Pt. Notably, Pt NCs were significantly aggregated at the site of tumor inoculation in mice and exhibited satisfactory in vivo inhibition of the increase in tumor weight and its size under the premise of not damaging the liver and spleen. Thus, the merits of versatile Pt NCs included facile target recognition, explicit cellular uptake behavior, and therapeutic efficacy in vivo, thereby hinting at their promising prospects for the clinical diagnosis and treatment of hematological malignancies.