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Updated: Jun 29, 2025
Preparation and Characterization of Lipophilic Doxorubicin Pro-drug Micelles
Published on: August 2, 2016
Potent cancer therapy by liposome microstructure tailoring with active-to-passive targeting and shell-to-core
Mengxin Zhao1, Xiaodong Zhu1, Bailing Li2
1Department of Nanomedicine & Shanghai Key Lab of Cell Engineering, Naval Medical University, Shanghai, 200433, China.
Abstract:
Liposomes have been widely studied as drug carriers for clinical application, and the key issue is how to achieve effective delivery through targeting strategies. Even though certain cell-level targeting or EPR effect designs have been developed, reaching sufficient drug concentration in intracellular regions remains a challenge due to the singularity of functionality. Herein, benefiting from the unique features of tumor from tissue to cell, a dual-thermosensitive and dual-targeting liposome (DTSL) was creatively fabricated through fine microstructure tailoring, which holds intelligent both tissue-regulated active-to-passive binding and membrane-derived homologous-fusion (HF) properties. At the micro level, DTSL can actively capture tumor cells and accompany the enhanced HF effect stimulated by self-constriction, which achieves a synergistic promotion effect targeting tissues to cells. As a result, this first active-then passive targeting process makes drug delivery more accurate and effective, and after dynamic targeting into cells, the nucleus of DTSL undergoes further thermally responsive contraction, fully releasing internal drugs. In vivo experiments showed that liposomes with dual targeting and dual thermosensitive features almost completely inhibited tumor growth. Summarized, these results provide a reference for a rational design and microstructural tailoring of the liposomal co-delivery system of drugs, suggesting that active-to-passive dual-targeting DTSL can function as a new strategy for cancer treatment.
Insights
Researchers developed dual-thermosensitive and dual-targeting liposomes (DTSL) for enhanced cancer treatment. These liposomes effectively target tumors from tissue to cell, significantly inhibiting growth and improving drug delivery.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Drug Delivery Systems
Background:
- Liposomes are crucial drug carriers, but effective intracellular delivery via targeting remains a challenge.
- Existing strategies like cell-level targeting or EPR effect have limitations in achieving sufficient intracellular drug concentrations.
- Tumor-specific characteristics from tissue to cellular levels offer opportunities for advanced targeting strategies.
Purpose of the Study:
- To design and fabricate a novel dual-thermosensitive and dual-targeting liposome (DTSL) for improved cancer therapy.
- To leverage unique tumor microenvironment features for enhanced drug delivery accuracy and efficacy.
- To investigate the synergistic targeting and drug release mechanisms of the DTSL system.
Main Methods:
- Fabrication of DTSL through microstructure tailoring, incorporating dual-thermosensitive and dual-targeting properties.
- Utilizing intelligent tissue-regulated active-to-passive binding and membrane-derived homologous-fusion (HF) properties.
- Evaluating DTSL performance through in vivo experiments to assess tumor inhibition and drug release dynamics.
Main Results:
- DTSL demonstrated active tumor cell capture and enhanced HF effect, achieving synergistic targeting from tissue to cell.
- The active-then-passive targeting process led to more accurate and effective drug delivery.
- Intracellularly, DTSL's nucleus underwent thermally responsive contraction, ensuring complete drug release and almost complete tumor growth inhibition in vivo.
Conclusions:
- The developed DTSL system offers a novel strategy for cancer treatment by combining dual targeting and dual thermosensitive properties.
- Rational design and microstructural tailoring of liposomal systems are crucial for effective co-delivery of drugs.
- Active-to-passive dual-targeting DTSL shows significant potential as an advanced therapeutic approach for cancer.
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