P-glycoprotein (P-gp) overexpressed mutidrug resistance (MDR) is currently a key factor limiting the effectiveness of breast cancer chemotherapy. Systemic administration based on P-gp-associated mechanism leads to severe toxic side effects. Here, we designed a T7 peptide -modified mixed liposome (T7-MLP@DTX/SchB) that, by active targeting co -delivering chemotherapeutic agents and P-gp inhibitors, harnessed synergistic effects to improve the treatment of MDR breast cancer. This study established drug -resistant cell models and animal models. Subsequently, comprehensive evaluations involving cell uptake, cell apoptosis, cellular toxicity assays, in vivo tumor -targeting capability, and anti -tumor activity assays were conducted to assess the drug resistance reversal effects of T7-MLP@DTX/SchB. Additionally, a systematic assessment of the biosafety profile of T7MLP@DTX/SchB was executed, including blood profiles, biochemical markers, and histopathological examination. It was found that this co -delivery strategy successfully exerted the synergistic effects, since there was a significant tumor growth inhibitory effect on multidrug-resistant breast cancer. Targeted modification with T7 peptide enhanced the therapeutic efficacy remarkably, while vastly ameliorating the biocompatibility compared to free drugs. The intriguing results supported the promising potential use of T7-MLP@DTX/SchB in overcoming MDR breast cancer treatment.
机构:
Rutgers State Univ, Dept Pharmaceut, Ernest Mario Sch Pharm, Piscataway, NJ 08854 USARutgers State Univ, Dept Pharmaceut, Ernest Mario Sch Pharm, Piscataway, NJ 08854 USA
Saad, Maha
Garbuzenko, Olga B.
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Rutgers State Univ, Dept Pharmaceut, Ernest Mario Sch Pharm, Piscataway, NJ 08854 USARutgers State Univ, Dept Pharmaceut, Ernest Mario Sch Pharm, Piscataway, NJ 08854 USA
Garbuzenko, Olga B.
Minko, Tamara
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Rutgers State Univ, Dept Pharmaceut, Ernest Mario Sch Pharm, Piscataway, NJ 08854 USARutgers State Univ, Dept Pharmaceut, Ernest Mario Sch Pharm, Piscataway, NJ 08854 USA
机构:
Sichuan Univ, Natl Engn Res Ctr Biomat, 29 Wangjiang Rd, Chengdu 610064, Sichuan, Peoples R ChinaSichuan Univ, Natl Engn Res Ctr Biomat, 29 Wangjiang Rd, Chengdu 610064, Sichuan, Peoples R China
Cui, Yani
Yang, Yuedi
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Sichuan Univ, Natl Engn Res Ctr Biomat, 29 Wangjiang Rd, Chengdu 610064, Sichuan, Peoples R ChinaSichuan Univ, Natl Engn Res Ctr Biomat, 29 Wangjiang Rd, Chengdu 610064, Sichuan, Peoples R China
Yang, Yuedi
Ma, Mengcheng
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Sichuan Univ, Natl Engn Res Ctr Biomat, 29 Wangjiang Rd, Chengdu 610064, Sichuan, Peoples R ChinaSichuan Univ, Natl Engn Res Ctr Biomat, 29 Wangjiang Rd, Chengdu 610064, Sichuan, Peoples R China
Ma, Mengcheng
Xu, Yang
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Sichuan Univ, Natl Engn Res Ctr Biomat, 29 Wangjiang Rd, Chengdu 610064, Sichuan, Peoples R ChinaSichuan Univ, Natl Engn Res Ctr Biomat, 29 Wangjiang Rd, Chengdu 610064, Sichuan, Peoples R China
Xu, Yang
Sui, Junhui
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Sichuan Univ, Natl Engn Res Ctr Biomat, 29 Wangjiang Rd, Chengdu 610064, Sichuan, Peoples R ChinaSichuan Univ, Natl Engn Res Ctr Biomat, 29 Wangjiang Rd, Chengdu 610064, Sichuan, Peoples R China
Sui, Junhui
Li, Huifang
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Sichuan Univ, West China Hosp, Res Core Facil, Bldg B2,88 Keyuan South St, Chengdu 610041, Sichuan, Peoples R ChinaSichuan Univ, Natl Engn Res Ctr Biomat, 29 Wangjiang Rd, Chengdu 610064, Sichuan, Peoples R China
Li, Huifang
Liang, Jie
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Sichuan Univ, Natl Engn Res Ctr Biomat, 29 Wangjiang Rd, Chengdu 610064, Sichuan, Peoples R ChinaSichuan Univ, Natl Engn Res Ctr Biomat, 29 Wangjiang Rd, Chengdu 610064, Sichuan, Peoples R China
Liang, Jie
Sun, Yong
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Sichuan Univ, Natl Engn Res Ctr Biomat, 29 Wangjiang Rd, Chengdu 610064, Sichuan, Peoples R ChinaSichuan Univ, Natl Engn Res Ctr Biomat, 29 Wangjiang Rd, Chengdu 610064, Sichuan, Peoples R China
Sun, Yong
Fan, Yujiang
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Sichuan Univ, Natl Engn Res Ctr Biomat, 29 Wangjiang Rd, Chengdu 610064, Sichuan, Peoples R ChinaSichuan Univ, Natl Engn Res Ctr Biomat, 29 Wangjiang Rd, Chengdu 610064, Sichuan, Peoples R China
Fan, Yujiang
Zhang, Xingdong
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Sichuan Univ, Natl Engn Res Ctr Biomat, 29 Wangjiang Rd, Chengdu 610064, Sichuan, Peoples R ChinaSichuan Univ, Natl Engn Res Ctr Biomat, 29 Wangjiang Rd, Chengdu 610064, Sichuan, Peoples R China
机构:
Chungnam Natl Univ, Coll Pharm, Daejeon 34134, South Korea
Chungnam Natl Univ, Inst Drug Res & Dev, Daejeon 34134, South KoreaChungnam Natl Univ, Coll Pharm, Daejeon 34134, South Korea