Presentation Information
[P01-139]Development of Radiopaque Hydrogel-in-Liposomes for Enhanced μCT Imaging and Anti-tumor Therapy
○Minkyung Kim1, Sang Min Lee1, Jae-Young Lee1,2 (1. College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University (Korea) (Korea), 2. Natural Products Research Institute, Seoul National University (Korea) (Korea))
Keywords:
Hydrogel-in-Liposomes,Theranostics,μCT imaging,targeted delivery
[Purpose]
The study aims to develop a Radiopaque Hydrogel-in-Liposome (RHL) system for simultaneous micro-computed tomography (μCT) imaging and targeted delivery of anti-cancer agents. Traditional liposomes often suffer from physical instability and an initial burst release of encapsulated drugs. By incorporating a cross-linked PEG hydrogel core, the researchers sought to enhance the structural integrity and controlled release properties of the carrier. This platform is designed to address the unmet needs of efficient tumor therapy and precise diagnosis in a single nano-platform.
[Method]
The RHLs (F2) were fabricated using the thin-film hydration method with EPC and cholesterol. A mixture of PEGMA, PEGDA, and the photo-initiator HMPP was encapsulated and polymerized via UV irradiation to form the internal hydrogel core. Doxorubicin (DOX) was loaded using an ammonium sulfate gradient (remote loading), while Iopamidol (IPD) served as the CT contrast agent. The formation of the hydrogel core was verified through ATR-FTIR, 1H NMR, and selective solvent extraction.
[Results]
The RHLs exhibited a uniform spherical shape with a mean diameter of approximately 160 nm and a negative zeta potential. Compared to conventional radiopaque liposomes (F1), RHLs significantly reduced the initial burst release of DOX and minimized IPD leakage. In vitro studies showed that RHLs achieved 1.72-fold higher cellular uptake in SCCVII cells than F1, primarily through clathrin-mediated endocytosis. In vivo, the system demonstrated superior tumor targeting (EPR effect) and enhanced CT contrast efficiency in tumor-xenografted mice.
[Consideration]
The internal PEG hydrogel network acts as an additional diffusion barrier, which is key to the sustained drug release and improved stability in serum. Interestingly, the hydrogel core triggered an additional internalization mechanism that conventional liposomes did not utilize in this model. This suggests that the mechanical or structural properties of the lipogel can actively influence biological interactions. Furthermore, the pH-dependent release profile ensures that the therapeutic payload is preferentially released within the acidic tumor microenvironment.
[Conclusion]
The RHL system successfully integrates diagnostic imaging and therapeutic functionalities into a single biocompatible platform. It effectively overcomes the limitations of traditional liposomes by providing better stability and controlled release. The findings confirm that RHLs significantly improve anti-tumor efficacy and CT imaging performance in vivo.
The study aims to develop a Radiopaque Hydrogel-in-Liposome (RHL) system for simultaneous micro-computed tomography (μCT) imaging and targeted delivery of anti-cancer agents. Traditional liposomes often suffer from physical instability and an initial burst release of encapsulated drugs. By incorporating a cross-linked PEG hydrogel core, the researchers sought to enhance the structural integrity and controlled release properties of the carrier. This platform is designed to address the unmet needs of efficient tumor therapy and precise diagnosis in a single nano-platform.
[Method]
The RHLs (F2) were fabricated using the thin-film hydration method with EPC and cholesterol. A mixture of PEGMA, PEGDA, and the photo-initiator HMPP was encapsulated and polymerized via UV irradiation to form the internal hydrogel core. Doxorubicin (DOX) was loaded using an ammonium sulfate gradient (remote loading), while Iopamidol (IPD) served as the CT contrast agent. The formation of the hydrogel core was verified through ATR-FTIR, 1H NMR, and selective solvent extraction.
[Results]
The RHLs exhibited a uniform spherical shape with a mean diameter of approximately 160 nm and a negative zeta potential. Compared to conventional radiopaque liposomes (F1), RHLs significantly reduced the initial burst release of DOX and minimized IPD leakage. In vitro studies showed that RHLs achieved 1.72-fold higher cellular uptake in SCCVII cells than F1, primarily through clathrin-mediated endocytosis. In vivo, the system demonstrated superior tumor targeting (EPR effect) and enhanced CT contrast efficiency in tumor-xenografted mice.
[Consideration]
The internal PEG hydrogel network acts as an additional diffusion barrier, which is key to the sustained drug release and improved stability in serum. Interestingly, the hydrogel core triggered an additional internalization mechanism that conventional liposomes did not utilize in this model. This suggests that the mechanical or structural properties of the lipogel can actively influence biological interactions. Furthermore, the pH-dependent release profile ensures that the therapeutic payload is preferentially released within the acidic tumor microenvironment.
[Conclusion]
The RHL system successfully integrates diagnostic imaging and therapeutic functionalities into a single biocompatible platform. It effectively overcomes the limitations of traditional liposomes by providing better stability and controlled release. The findings confirm that RHLs significantly improve anti-tumor efficacy and CT imaging performance in vivo.
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