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Purpose <p>Conventional chemotherapy often lacks tumor selectivity, leading to systemic toxicity and damage to healthy tissues. Nanoparticles (NPs) offer a promising solution by enabling targeted drug delivery, thereby improving therapeutic efficacy and reducing adverse effects. In this study, we developed an NP-based delivery system using mesoporous silica nanoparticles (MSNs) to enhance the targeted delivery of doxorubicin (DOX) for breast cancer treatment.</p> Methods <p>MSNs were synthesized using a biphasic stratification method and functionalized with a pH-responsive poly-L-histidine (PLH) polymer to achieve controlled drug release in the acidic tumor microenvironment. Hyaluronic acid (HA) was conjugated to facilitate tumor-specific targeting via CD44 receptor-mediated endocytosis in MDA-MB-231 triple-negative breast carcinomas. This dual strategy, along with the enhanced permeability and retention (EPR) effect, aimed to improve therapeutic efficacy while minimizing off-target effects.</p> Results <p>In vitro analysis confirmed efficient cellular uptake, cytotoxicity, and proapoptotic activity of the functionalized MSNs in target cells. In vivo biodistribution analysis demonstrated preferential accumulation in tumors, with minimal retention in nontarget tissues. These findings correlated with significant tumor suppression and negligible systemic toxicity.</p> Conclusion <p>This MSN-based targeted delivery system represents a promising approach for improving the efficacy and safety of breast cancer chemotherapy.</p>

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Fabrication of poly-L-histidine-coated mesoporous silica nanoparticles with hyaluronic acid for targeted doxorubicin delivery

  • 期刊论文

  • 发表日期：

    2025年9月11日

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  • Prajeena Karmacharya,
  • Amit Shrestha,
  • Beomsu Kim,
  • Huy Xuan Luong,
  • Jeonghwan Kim,
  • Basavaraj Rudragouda Patil,
  • Jong Oh Kim

摘要

Purpose

Conventional chemotherapy often lacks tumor selectivity, leading to systemic toxicity and damage to healthy tissues. Nanoparticles (NPs) offer a promising solution by enabling targeted drug delivery, thereby improving therapeutic efficacy and reducing adverse effects. In this study, we developed an NP-based delivery system using mesoporous silica nanoparticles (MSNs) to enhance the targeted delivery of doxorubicin (DOX) for breast cancer treatment.

Methods

MSNs were synthesized using a biphasic stratification method and functionalized with a pH-responsive poly-L-histidine (PLH) polymer to achieve controlled drug release in the acidic tumor microenvironment. Hyaluronic acid (HA) was conjugated to facilitate tumor-specific targeting via CD44 receptor-mediated endocytosis in MDA-MB-231 triple-negative breast carcinomas. This dual strategy, along with the enhanced permeability and retention (EPR) effect, aimed to improve therapeutic efficacy while minimizing off-target effects.

Results

In vitro analysis confirmed efficient cellular uptake, cytotoxicity, and proapoptotic activity of the functionalized MSNs in target cells. In vivo biodistribution analysis demonstrated preferential accumulation in tumors, with minimal retention in nontarget tissues. These findings correlated with significant tumor suppression and negligible systemic toxicity.

Conclusion

This MSN-based targeted delivery system represents a promising approach for improving the efficacy and safety of breast cancer chemotherapy.