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<p>Effective drug accumulation at tumor sites remains a critical challenge in cancer therapy due to poor targeting and off-target effects. This study leverages bioorthogonal chemistry to develop a novel liposome-based drug delivery system designed to enhance tumor-specific accumulation and achieve controlled drug release for improved therapeutic outcomes. DBCO- and azide-modified liposomes were engineered to optimize encapsulation efficiency, stability, and sustained drug release. Their performance was evaluated through in vitro cellular assays to assess uptake and toxicity, alongside in vivo biodistribution and efficacy studies in tumor-bearing models. The bioorthogonal liposomes demonstrated significantly enhanced tumor accumulation compared to free doxorubicin and conventional liposomes, achieving a tumor inhibition rate of 60%. In vitro experiments confirmed improved cellular uptake and retention without additional toxicity, while in vivo results highlighted superior therapeutic efficacy and reduced systemic toxicity, as evidenced by increased tumor apoptosis, suppressed proliferation, and minimal body weight loss. This study underscores the potential of bioorthogonal liposomes as a precise drug delivery platform, offering enhanced tumor targeting, better efficacy, and lower toxicity. These findings pave the way for next-generation targeted cancer therapies, with future efforts aimed at refining liposome design for clinical translation.</p>

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Bioorthogonal liposome-based sequential drug delivery system for enhanced tumor accumulation and targeted therapy

  • 期刊论文

  • 发表日期：

    2025年10月23日

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  • Yang Wang,
  • Wen Zheng,
  • Junjie Yan,
  • Lizhen Wang,
  • Donghui Pan,
  • Yuping Xu,
  • Chongyang Chen,
  • Xueyan Zhou,
  • Xinyu Wang,
  • Min Yang

摘要

Effective drug accumulation at tumor sites remains a critical challenge in cancer therapy due to poor targeting and off-target effects. This study leverages bioorthogonal chemistry to develop a novel liposome-based drug delivery system designed to enhance tumor-specific accumulation and achieve controlled drug release for improved therapeutic outcomes. DBCO- and azide-modified liposomes were engineered to optimize encapsulation efficiency, stability, and sustained drug release. Their performance was evaluated through in vitro cellular assays to assess uptake and toxicity, alongside in vivo biodistribution and efficacy studies in tumor-bearing models. The bioorthogonal liposomes demonstrated significantly enhanced tumor accumulation compared to free doxorubicin and conventional liposomes, achieving a tumor inhibition rate of 60%. In vitro experiments confirmed improved cellular uptake and retention without additional toxicity, while in vivo results highlighted superior therapeutic efficacy and reduced systemic toxicity, as evidenced by increased tumor apoptosis, suppressed proliferation, and minimal body weight loss. This study underscores the potential of bioorthogonal liposomes as a precise drug delivery platform, offering enhanced tumor targeting, better efficacy, and lower toxicity. These findings pave the way for next-generation targeted cancer therapies, with future efforts aimed at refining liposome design for clinical translation.