Presentation Information
[P01-121]Reprogramming the MAP Regimen via Bone-Targeted Albumin Nanoclusters for Enhanced Osteosarcoma Therapy
○Jae-Young Lee1,2, So-Yeol Yoo1,2 (1. College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University (Korea), 2. Natural Products Research Institute, Seoul National University (Korea))
Keywords:
Osteosarcoma,MAP regimen,Albumin nanoclusters,Bone tumor-targeted delivery,Thiamine pyrophosphate
[Purpose] Current osteosarcoma treatment relies on the MAP regimen (methotrexate, doxorubicin, and cisplatin), yet therapeutic improvements have largely focused on modifying drug combinations rather than enhancing delivery efficiency. This study aimed to develop a bone-targeted nanoplatform to potentiate the efficacy of the MAP regimen by improving drug localization and synergistic action within the tumor microenvironment.
[Method] Human serum albumin (HSA)-based nanoclusters were engineered and functionalized with thiamine pyrophosphate (TPP) to enable selective affinity toward hydroxyapatite-rich bone tumors. Methotrexate and doxorubicin were incorporated into the nanoclusters via hydrophobic interactions, while cisplatin was administered in its free form to maintain the conventional MAP framework. Physicochemical properties, hydroxyapatite-binding affinity, and drug release behaviors were characterized. In vitro cytotoxicity and synergy were evaluated in HOS/MNNG osteosarcoma cells. In vivo tumor accumulation and therapeutic efficacy were assessed using an orthotopic osteosarcoma mouse model.
[Results] TPP-functionalized nanoclusters exhibited significantly enhanced binding affinity to hydroxyapatite compared to non-modified counterparts, indicating improved targeting capability. In vitro studies demonstrated that the nanocluster-assisted MAP regimen produced stronger synergistic anticancer effects than the conventional formulation. In vivo imaging confirmed increased tumor accumulation of TPP-decorated nanoclusters. Consequently, the modified MAP regimen achieved superior tumor growth suppression without additional systemic toxicity.
[Consideration] The improved therapeutic outcome can be attributed to enhanced drug localization within the bone tumor microenvironment and the resulting amplification of drug synergy. The use of TPP as a biocompatible targeting ligand provides a safer alternative to conventional bone-targeting moieties, while preserving strong hydroxyapatite affinity. This approach highlights the importance of delivery system design in maximizing the efficacy of established combination therapies.
[Conclusion] This study demonstrates that re-engineering the MAP regimen using bone-targeted albumin nanoclusters significantly enhances its therapeutic performance. The proposed strategy offers a promising and translationally relevant approach for improving osteosarcoma treatment outcomes.
[Method] Human serum albumin (HSA)-based nanoclusters were engineered and functionalized with thiamine pyrophosphate (TPP) to enable selective affinity toward hydroxyapatite-rich bone tumors. Methotrexate and doxorubicin were incorporated into the nanoclusters via hydrophobic interactions, while cisplatin was administered in its free form to maintain the conventional MAP framework. Physicochemical properties, hydroxyapatite-binding affinity, and drug release behaviors were characterized. In vitro cytotoxicity and synergy were evaluated in HOS/MNNG osteosarcoma cells. In vivo tumor accumulation and therapeutic efficacy were assessed using an orthotopic osteosarcoma mouse model.
[Results] TPP-functionalized nanoclusters exhibited significantly enhanced binding affinity to hydroxyapatite compared to non-modified counterparts, indicating improved targeting capability. In vitro studies demonstrated that the nanocluster-assisted MAP regimen produced stronger synergistic anticancer effects than the conventional formulation. In vivo imaging confirmed increased tumor accumulation of TPP-decorated nanoclusters. Consequently, the modified MAP regimen achieved superior tumor growth suppression without additional systemic toxicity.
[Consideration] The improved therapeutic outcome can be attributed to enhanced drug localization within the bone tumor microenvironment and the resulting amplification of drug synergy. The use of TPP as a biocompatible targeting ligand provides a safer alternative to conventional bone-targeting moieties, while preserving strong hydroxyapatite affinity. This approach highlights the importance of delivery system design in maximizing the efficacy of established combination therapies.
[Conclusion] This study demonstrates that re-engineering the MAP regimen using bone-targeted albumin nanoclusters significantly enhances its therapeutic performance. The proposed strategy offers a promising and translationally relevant approach for improving osteosarcoma treatment outcomes.
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