Scholarlink

Purpose <p>To improve the targeted therapy of hepatocellular carcinoma (HCC), SP94-modified calcium phosphate lipid nanoparticles loaded with Bcl-2 siRNA and doxorubicin (SP94-LCP/DOX&amp;Bcl-2 siRNA) were prepared.</p> Methods <p>SP94-LCP/DOX&amp;Bcl-2 siRNA was fabricated via reversed-phase microemulsion. Its physicochemical properties (particle size, zeta potential, morphology), pharmaceutical performance (drug loading, encapsulation efficiency, stability,<i> in vitro</i> release), and <i>in vitro</i> activities (targeting, cytotoxicity, apoptosis, apoptosis-related proteins) were evaluated using HepG2 cells via cellular uptake, wound healing, Hoechst 33,258 staining, MTT, and Western blot assays. <i>In vivo</i> antitumor efficacy was tested in HepG2 xenograft nude mice.</p> Results <p>SP94-LCP/DOX&amp;Bcl-2 siRNA had a mean diameter of 130&#xa0;nm and a zeta potential of 20&#xa0;mV, showing a spherical morphology with uniform distribution. The encapsulation efficiency of siRNA reached 92% and that of doxorubicin is 81%. It exhibited good stability and a significant sustained-release effect. SP94-LCP/DOX&amp;Bcl-2 siRNA significantly reduced the IC₅₀ values of DOX + Bcl-2siRNA, and enhanced the uptake capacity of HepG2 cells for LCP. It remarkably inhibited the migration ability of HepG2 cells, concomitantly downregulating Bcl-2 and upregulating Bax expression, thereby facilitating apoptotic cell death. SP94-LCP/DOX&amp;Bcl-2 siRNA could better inhibit tumor growth in mice and reduce the toxic and side effects on normal tissues of mice.</p> Conclusions <p>In this study, SP94-LCP/DOX&amp;Bcl-2 siRNA was successfully prepared. It exhibited remarkable targeting ability and antitumor activity, significantly enhancing the therapeutic effect of doxorubicin and siRNA on HCC. The construction of this drug delivery system provided a novel strategy for the clinical treatment of HCC.</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

Preparation of SP94-Modified Calcium Phosphate Lipid Nanoparticles Loaded with Bcl-2 siRNA and Doxorubicin and Their Targeted Therapeutic Effect on Hepatocellular Carcinoma

  • 期刊论文

  • 发表日期：

    2026年5月11日

查看全文
  • Kailun Ma,
  • Jinfei Yao,
  • Yueyi Deng,
  • Tianqi Lan,
  • Chengyun Yan

摘要

Purpose

To improve the targeted therapy of hepatocellular carcinoma (HCC), SP94-modified calcium phosphate lipid nanoparticles loaded with Bcl-2 siRNA and doxorubicin (SP94-LCP/DOX&Bcl-2 siRNA) were prepared.

Methods

SP94-LCP/DOX&Bcl-2 siRNA was fabricated via reversed-phase microemulsion. Its physicochemical properties (particle size, zeta potential, morphology), pharmaceutical performance (drug loading, encapsulation efficiency, stability, in vitro release), and in vitro activities (targeting, cytotoxicity, apoptosis, apoptosis-related proteins) were evaluated using HepG2 cells via cellular uptake, wound healing, Hoechst 33,258 staining, MTT, and Western blot assays. In vivo antitumor efficacy was tested in HepG2 xenograft nude mice.

Results

SP94-LCP/DOX&Bcl-2 siRNA had a mean diameter of 130 nm and a zeta potential of 20 mV, showing a spherical morphology with uniform distribution. The encapsulation efficiency of siRNA reached 92% and that of doxorubicin is 81%. It exhibited good stability and a significant sustained-release effect. SP94-LCP/DOX&Bcl-2 siRNA significantly reduced the IC₅₀ values of DOX + Bcl-2siRNA, and enhanced the uptake capacity of HepG2 cells for LCP. It remarkably inhibited the migration ability of HepG2 cells, concomitantly downregulating Bcl-2 and upregulating Bax expression, thereby facilitating apoptotic cell death. SP94-LCP/DOX&Bcl-2 siRNA could better inhibit tumor growth in mice and reduce the toxic and side effects on normal tissues of mice.

Conclusions

In this study, SP94-LCP/DOX&Bcl-2 siRNA was successfully prepared. It exhibited remarkable targeting ability and antitumor activity, significantly enhancing the therapeutic effect of doxorubicin and siRNA on HCC. The construction of this drug delivery system provided a novel strategy for the clinical treatment of HCC.