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Updated: Feb 5, 2026

Metabolic Glycoengineering of Sialic Acid Using N-acyl-modified Mannosamines
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Sialic Acid-Functionalized pH-Triggered Micelles for Enhanced Tumor Tissue Accumulation and Active Cellular

Xiao-Ling Xu1, Kong-Jun Lu1, Meng-Lu Zhu2

  • 1Institute of Pharmaceutics, College of Pharmaceutical Sciences , Zhejiang University , Hangzhou 310058 , PR China.

ACS Applied Materials & Interfaces
|September 5, 2018
PubMed

Insights

A novel pH-triggered, sialic acid-targeted drug delivery system (SPD) effectively delivered doxorubicin (DOX) to tumors. This targeted approach enhanced accumulation and showed significant antitumor effects in both orthotopic and ectopic hepatocarcinoma models.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Targeted and stimuli-sensitive drug delivery systems (DDSs) aim to improve antitumor efficacy.
  • Clinical application is hindered by challenges in tumor targeting and understanding stimuli-responsive DDS behavior in different tumor types.

Purpose of the Study:

  • To develop and evaluate a pH-triggered micelle with sialic acid (SA)-driven targeting ability for enhanced drug delivery.
  • To investigate the efficacy of this system in both orthotopic and ectopic hepatocarcinoma models.

Main Methods:

  • A novel SA-poly(ethylene glycol)-hydrazone linker-doxorubicin (SPD) micelle was synthesized.
  • DOX-loaded SPDD micelles were characterized for drug release kinetics and tumor accumulation.
  • Antitumor efficacy and metastasis were assessed in orthotopic and ectopic hepatocarcinoma models.

Main Results:

  • SPDD micelles exhibited sustained doxorubicin release, accelerated in the acidic tumor microenvironment.
  • SPD micelles showed a 2.3-fold increase in tumor accumulation compared to non-targeted micelles.
  • E-selectin interaction enhanced micelle accumulation and cellular internalization.
  • Significant reduction in tumor volume and metastasis was observed in vivo.

Conclusions:

  • SA-driven targeted DDS with a pH-responsive switch demonstrates effective hepatocarcinoma treatment potential.
  • This system shows promise for both orthotopic and ectopic tumor models.
  • The findings support the clinical translation of advanced DDS for cancer therapy.
Keywords:
E-selectinhepatocarcinomaorthotopicpH-responsivesialic acid

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