Carrier-Free Cisplatin-Dactolisib Nanoparticles for Enhanced Synergistic Antitumor Efficacy.

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Tác giả: Xianfeng Chen, Sevil Gonca, Minhuan Lan, Bin-Zhi Qian, Norbert Radacsi, Qiuxia Tan, Mei Zhang

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: United States : ACS biomaterials science & engineering , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 676570

Cisplatin (CDDP) is one of the most commonly used chemotherapeutic agents for solid tumors and hematologic malignancy. However, its therapeutic outcomes have remained unsatisfactory due to severe side effects, a short elimination half-life, the emergence of drug resistance, and the induction of metastasis. Combination with other chemotherapeutic agents has been proposed as one strategy to address the drawbacks of CDDP-based therapy. Therefore, this study aimed to boost the antitumor efficacy of cisplatin (CDDP) with a PI3K/mTOR dual inhibitor, dactolisib (BEZ), via a carrier-free codelivery system based on the self-assembly of the coordinated CDDP-BEZ. The synthesized CDDP-BEZ nanoparticles (NPs) possess sensitive pH-responsiveness, facilitating the delivery of both drugs to cancer cells. CDDP-BEZ NPs specifically enhanced cytotoxicity in cancer cells due to the synergy between cisplatin and dactolisib, resulting in augmented DNA damage, activation of mitochondria-dependent apoptosis, and increased inhibition on the PI3K/mTOR signaling axis. The inhibition of tumor migration and metastasis by CDDP-BEZ NPs was observed both in vitro and in vivo. Our data suggest that CDDP-BEZ NPs could serve as a safe and effective platform to maximize the synergy between both drugs in combating cancer, presenting a strategy to promote the therapeutic efficacy of platinum-based chemotherapeutic agents by combining them with PI3K inhibitors.
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