Jie Yu,Xidong He,Qingfei Zhang,Dongfang Zhou,Zigui Wang,Yubin Huang
Theranostics of platinum (Pt)-based chemotherapy are able to self-track the biodistribution and pharmacokinetics while performing therapeutic effects. Pt-based CT imaging is expected to visualize and monitor the tumor throughout the entire tumor inhibition stage. However, a sufficient Pt concentration is necessary for CT imaging, which may bring about severe nephrotoxicity. A Bio-Pt-I compound is designed and synthesized by conjugation of iodine and biotin to the structure of Pt and further self-assembles into nanoparticles. The introduction of iodine not only enhances the CT imaging signal with a much lower dose of Pt but also overcomes the resistance of tumor cells to Pt-containing nanomedicine by inhibiting the expression of Bcl-2. Furthermore, biotin-mediated tumor targeting increases drug accumulation in tumors. This work combines CT imaging based self-track with efficient cisplatin-resistance reversion ability, which may promote the clinical transformation of Pt-containing nanomedicine.
Sonodynamic therapy (SDT) is an efficient non-invasive strategy for treating breast cancer. However, the therapeutic efficacy of SDT is greatly limited by various defense mechanisms in the tumor microenvironment, particularly the overexpression of B-cell lymphoma-2 (Bcl-2). In this study, based on drug self-delivery systems, a carrier-free ultrasound-responsive polyphenol nanonetwork (GTC) was developed to enhance SDT by inhibiting Bcl-2. A one-pot method, involving the interaction of the polyphenolic Bcl-2 inhibitor gossypol (GOS), transferrin, and the sonosensitizer chlorin e6 (Ce6), was used to synthesize the GTC. The GTC was efficiently internalized by MDA-MB-231 and 4T1 cells through specific binding to transferrin receptors, and no external carriers were needed. After cellular internalization, GOS increased the lethality of Ce6-mediated SDT by reducing the expression of the Bcl-2 protein, which caused multiple toxic effects. RNA-seq analysis confirmed the transcriptomic alterations in oxidative stress and apoptotic pathways induced by the GTC nanosystem. In vivo studies revealed that GOS-assisted SDT not only eliminated tumors through sonodynamic effects and triggered immunogenic cell death but also enhanced sono-immunotherapy, thus effectively suppressing distant tumors and metastasis. This study might provide insights into carrier-free nanomedicines for SDT-based synergistic tumor therapy.
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