Synergistic anti-tumor therapy by a homotypic cell membrane-cloaked biomimetic nanocarrier with exceptionally potent activity against hepatic carcinoma

Hepatic carcinoma (HC) is the sixth most frequently occurring malignancies and the third leading cause of cancer death worldwide. Sepantronium bromide (YM155) is a small molecule inhibitor of survivin, which has broad-spectrum anticancer therapeutic effects in various xenograft models. However, several-day continuous infusion is required to achieve greater anti-tumor efficacy because of rapid elimination from the blood circulation. Herein, a SMMC-7721 cancerous cyto-membrane-cloaked drug delivery system (DDS) (named as iM7721@GQD-YM), was developed for co-encapsulation of YM155 and graphene quantum dots (GQDs). Cytomembrane coating endowed iM7721@GQD-YM with effective targeting for homologous HC cells, excellent biocompatibility and favorable immunocompatibility for in vivo application. Surface decoration of iRGD peptide further enhanced its tumor targeting activity by iRGD-integrin recognition. In addition, under the irradiation of near-infrared ray (NIR), GQDs can directly kill tumors through photothermal effect and cause cell membrane rupture, accurately releasing YM155 at tumor sites. The physicochemical properties, in vivo andex vivo anti-tumor efficacy, and mechanisms of iM7721@GQD-YM nanoparticles (NPs) were systematically investigated in this work. The experimental results clearly indicate that the versatile biomimetic DDS holds great potential for the treatment of HC, which merits further investigation in both pre-clinical and clinical studies.