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<p>This study aims to create glyco-based nanoparticles (NPs) with high drug-loading capability for targeted cancer treatment, specifically against MDA-MB-231 breast cancer cells. Traditional NPs have faced limitations due to low drug-loading capacities, leading to suboptimal therapeutic effectiveness and significant side effects. To overcome these limitations, DOX@pB-pM NP were synthesized using a self-assembly combination method of two poly(ε-caprolactone) (PCL) based polymers, mannoside-<i>b</i>-PCL (pM) and phenylboronic acid (PBA)-mPEG-<i>t</i>-PCL (pB). The pM polymer synthesis includes a Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAc) reaction. DOX@pB-pM NP's mannose moiety is specifically engineered to target MDA-MB-231 cells, while the core of the NPs is made of hydrophobic, biodegradable polyester PCL. The functions of mPEG and PBA in the pB tri-block copolymer are to enhance biocompatibility and drug-loading efficiency, respectively. Additionally, mPEG can reduce nonspecific interactions. The PBA on the pB introduces a hydrophobic segment to the copolymer, which can improve the interaction with water-insoluble drugs, doxorubicin (DOX). The PBA moiety can also provide additional functionality, such as pH-responsive and H<sub>2</sub>O<sub>2</sub>-responsive drug release, which is particularly useful in targeting the tumor’s acidic and oxidative microenvironment. The PBA groups convert them to boronic acid and 4-(hydroxymethyl) phenol, which destroys the NP core and causes DOX release, resulting in cell death. The in vitro release profile of DOX from the DOX@pB-pM NPs was evaluated under various conditions, including different pH levels and the presence or absence of H<sub>2</sub>O<sub>2</sub>, to simulate the acidic tumor microenvironment. The cytotoxicity of the DOX@pB-pM NPs was assessed using the MTT assay, which demonstrated significant inhibition of MDA-MB-231 breast cancer cell growth by DOX@pB-pM NPs. By combining mannose for the targeting of MDA-MB-231 breast cancer cells and fine-tuning the ratio of pM and pB polymers, the NPs showed good therapeutic efficacy. Importantly, pB-pM NPs displayed good biocompatibility, with no significant effect on cell survival even at high concentrations, indicating their potential as safe drug carriers. These data show that DOX@pB-pM NPs can potentially improve cancer therapeutic efficacy and safety.</p> Graphical Abstract <p></p>

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Combination of mannoside and phenylboronic acid polycaprolactone polymers for doxorubicin-encapsulated polymersome nanomedicine targeting MDA-MB-231 cancer cells

  • 期刊论文

  • 发表日期：

    2025年3月22日

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  • Yung-Hsin Huang,
  • Govindan Sivakumar,
  • Rajiv Kamaraj,
  • Kai Yi Lim,
  • Yu-Xuan Chen,
  • Cheng-Han Liu,
  • Yi-Cheng Wang,
  • Hsuan-Ying Chen,
  • Tuck Whye Wong,
  • Yuan Wen Hau,
  • Chian-Hui Lai

摘要

This study aims to create glyco-based nanoparticles (NPs) with high drug-loading capability for targeted cancer treatment, specifically against MDA-MB-231 breast cancer cells. Traditional NPs have faced limitations due to low drug-loading capacities, leading to suboptimal therapeutic effectiveness and significant side effects. To overcome these limitations, DOX@pB-pM NP were synthesized using a self-assembly combination method of two poly(ε-caprolactone) (PCL) based polymers, mannoside-b-PCL (pM) and phenylboronic acid (PBA)-mPEG-t-PCL (pB). The pM polymer synthesis includes a Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAc) reaction. DOX@pB-pM NP's mannose moiety is specifically engineered to target MDA-MB-231 cells, while the core of the NPs is made of hydrophobic, biodegradable polyester PCL. The functions of mPEG and PBA in the pB tri-block copolymer are to enhance biocompatibility and drug-loading efficiency, respectively. Additionally, mPEG can reduce nonspecific interactions. The PBA on the pB introduces a hydrophobic segment to the copolymer, which can improve the interaction with water-insoluble drugs, doxorubicin (DOX). The PBA moiety can also provide additional functionality, such as pH-responsive and H2O2-responsive drug release, which is particularly useful in targeting the tumor’s acidic and oxidative microenvironment. The PBA groups convert them to boronic acid and 4-(hydroxymethyl) phenol, which destroys the NP core and causes DOX release, resulting in cell death. The in vitro release profile of DOX from the DOX@pB-pM NPs was evaluated under various conditions, including different pH levels and the presence or absence of H2O2, to simulate the acidic tumor microenvironment. The cytotoxicity of the DOX@pB-pM NPs was assessed using the MTT assay, which demonstrated significant inhibition of MDA-MB-231 breast cancer cell growth by DOX@pB-pM NPs. By combining mannose for the targeting of MDA-MB-231 breast cancer cells and fine-tuning the ratio of pM and pB polymers, the NPs showed good therapeutic efficacy. Importantly, pB-pM NPs displayed good biocompatibility, with no significant effect on cell survival even at high concentrations, indicating their potential as safe drug carriers. These data show that DOX@pB-pM NPs can potentially improve cancer therapeutic efficacy and safety.

Graphical Abstract