Scholarlink

Purpose <p>Chemo-gene combination therapy offers a promising strategy to overcome the challenges of the tumor microenvironment, aiming to enhance therapeutic efficacy and reduce side effects. However, the distinct properties of nucleic acids and chemotherapeutic agents present significant challenges for their co-delivery using nanoparticles (NPs). This study proposes a novel nanoparticle delivery system based on π–π stacking interactions to facilitate the co-delivery of siRNA and irinotecan hydrochloride (IR).</p> Methods <p>A series of amphiphilic block copolymers with various aromatic side groups were synthesized via living ring-opening polymerization (ROP). Complexes of siRNA and IR were initially formed through electrostatic interactions. Subsequently, polymer/nucleic acid/chemotherapeutic composite NPs were assembled via π–π stacking interactions between the aromatic groups on the polymers and those on the IR molecules. Particle size (D<sub>h</sub>) and zeta potential (ζ) of NPs were measured by DLS. IR loading efficiency (EE) and loading capacity (LC) were determined by UV–Vis. HeLa-Luc cells were treated with polymer@siPLK1&amp;IR NPs to assess luciferase gene silencing and cytotoxicity via the MTT assay.</p> Results <p>Block copolymers with fine-tuned chemical structures and narrow molecular weight distributions were obtained via ROP of benzyl- or naphthyl-substituted valerolactone monomers using mPEG as the initiator. Selected polymers (PPLB6, PPLN5, PPLN6, and PPLV4) can bind siRNA&amp;IR complexes via π–π stacking interactions and form spherical NPs (D<sub>h</sub> = 121–173&#xa0;nm; ζ = − 11.8 to − 22.4 mV). Aromatic group-containing polymers achieved higher IR EE (57.5–63.9%) and LC (2.79–3.09 wt%) compared to the non-aromatic PPLV4 (EE: 55.1%, LC: 2.68%), confirming that π–π stacking interactions enhance drug loading. At pH 5.5, IR release reached approximately 57–70% over 72&#xa0;h, compared to 42–50% at pH 7.4. These NPs showed good storage stability for up to 7 days. In HeLa cells, aromatic group-containing polymer@siPLK1&amp;IR NPs (3&#xa0;µg/mL IR + 300 ng siPLK1 per well) induced greater cytotoxicity than polymer@IR NPs or non-aromatic PPLV4@siPLK1&amp;IR NPs, suggesting synergistic therapeutic effects and the benefit of π–π stacking interactions in the drug-loaded NPs.</p> Conclusion <p>The findings suggest that this π–π stacking-based nanoparticle delivery system effectively facilitates the co-delivery of siRNA and IR, providing valuable insights for the design of co-delivery systems for nucleic acids and chemotherapeutic agents.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Design and Evaluation of π-π Stacking-driven Polymeric Nanoparticles for Co-delivery of siRNA and Irinotecan

  • 期刊论文

  • 发表日期：

    2025年10月31日

查看全文
  • Wuping Shuai,
  • Ying Wang,
  • Yuanqin Su,
  • Tianrui Tong,
  • Qi Shuai,
  • Yunfeng Yan

摘要

Purpose

Chemo-gene combination therapy offers a promising strategy to overcome the challenges of the tumor microenvironment, aiming to enhance therapeutic efficacy and reduce side effects. However, the distinct properties of nucleic acids and chemotherapeutic agents present significant challenges for their co-delivery using nanoparticles (NPs). This study proposes a novel nanoparticle delivery system based on π–π stacking interactions to facilitate the co-delivery of siRNA and irinotecan hydrochloride (IR).

Methods

A series of amphiphilic block copolymers with various aromatic side groups were synthesized via living ring-opening polymerization (ROP). Complexes of siRNA and IR were initially formed through electrostatic interactions. Subsequently, polymer/nucleic acid/chemotherapeutic composite NPs were assembled via π–π stacking interactions between the aromatic groups on the polymers and those on the IR molecules. Particle size (Dh) and zeta potential (ζ) of NPs were measured by DLS. IR loading efficiency (EE) and loading capacity (LC) were determined by UV–Vis. HeLa-Luc cells were treated with polymer@siPLK1&IR NPs to assess luciferase gene silencing and cytotoxicity via the MTT assay.

Results

Block copolymers with fine-tuned chemical structures and narrow molecular weight distributions were obtained via ROP of benzyl- or naphthyl-substituted valerolactone monomers using mPEG as the initiator. Selected polymers (PPLB6, PPLN5, PPLN6, and PPLV4) can bind siRNA&IR complexes via π–π stacking interactions and form spherical NPs (Dh = 121–173 nm; ζ = − 11.8 to − 22.4 mV). Aromatic group-containing polymers achieved higher IR EE (57.5–63.9%) and LC (2.79–3.09 wt%) compared to the non-aromatic PPLV4 (EE: 55.1%, LC: 2.68%), confirming that π–π stacking interactions enhance drug loading. At pH 5.5, IR release reached approximately 57–70% over 72 h, compared to 42–50% at pH 7.4. These NPs showed good storage stability for up to 7 days. In HeLa cells, aromatic group-containing polymer@siPLK1&IR NPs (3 µg/mL IR + 300 ng siPLK1 per well) induced greater cytotoxicity than polymer@IR NPs or non-aromatic PPLV4@siPLK1&IR NPs, suggesting synergistic therapeutic effects and the benefit of π–π stacking interactions in the drug-loaded NPs.

Conclusion

The findings suggest that this π–π stacking-based nanoparticle delivery system effectively facilitates the co-delivery of siRNA and IR, providing valuable insights for the design of co-delivery systems for nucleic acids and chemotherapeutic agents.