2. Academic Validation
  3. Cyclic RGD modified dextran-quercetin polymer micelles for targeted therapy of breast cancer

Cyclic RGD modified dextran-quercetin polymer micelles for targeted therapy of breast cancer

  • Int J Biol Macromol. 2025 May;308(Pt 1):142272. doi: 10.1016/j.ijbiomac.2025.142272.
Chunpeng Yang 1,  Huiling Ma 1,  Ze Liang 1,  Ying Zhuang 1,  Litao Hu 1,  Kexin Zhang 1,  Leixiao Huang 1,  Min Li 2,  Shubiao Zhang 3,  Yuhong Zhen 4
Affiliations

Affiliations

  • 1 College of Pharmacy, Dalian Medical University, Dalian 116044, China.
  • 2 Molecular Imaging Precision Medical Collaborative Innovation Center, Shanxi Medical University, Taiyuan 030001, China; Department of Nuclear Medicine, The First Hospital of Shanxi Medical University, Shanxi Medical University, Taiyuan 030001, China. Electronic address: limin7839@sxmu.edu.cn.
  • 3 Key Laboratory of Biotechnology and Bioresources Utilization of Ministry of Education, Dalian Minzu University, Dalian 116600, China. Electronic address: zsb@dlnu.edu.cn.
  • 4 College of Pharmacy, Dalian Medical University, Dalian 116044, China. Electronic address: zhenyh@dmu.edu.cn.
PMID: 40118409 DOI: 10.1016/j.ijbiomac.2025.142272
Abstract

Quercetin is a natural flavonoid found in many Plants which has various pharmacological activities including antitumor effect. However, the poor water solubility and bioavailability limit the potential benefits of quercetin for patients. Thus, modifying quercetin structure and developing actively targeted drug delivery systems are extremely important for tumor precision therapy. Herein, polymer-drug conjugates dextran-quercetin (D-Q) and cRGD-dextran (R-D) were synthesized by grafting quercetin and polypeptide cRGDfk (Arg-Gly-Asp-(D-Phe)-Lys) to dextran. Then cRGD-modified dextran-quercetin polymer micelles (R-D-Q) were constructed by self-assembling of D-Q and R-D. R-D-Q micelles possessed appropriate particle size (133.4 nm), nearly neutral potential (8.14 mV) and excellent drug-loading efficiency (13.1 %) and achieved higher cytotoxicity, Apoptosis induction and penetration to human breast Cancer MCF-7 cells than the micelles unmodified with cRGD, which were ascribed to cRGD-integrin mediated transcytosis. R-D-Q micelles effectively suppressed tumor growth in tumor-bearing mice by delivering more quercetin throughout the tumor tissue. And R-D-Q micelles could promote the Apoptosis of tumor cells by activating p38 and JNK signal pathways and suppressing ERK signal pathway. In addition, R-D-Q micelles had no damage to normal tissues of mice at therapeutic dose. These results indicate promising prospects for R-D-Q micelles as an effective drug delivery system against tumor.

Keywords

Breast cancer; Dextran; Quercetin; Targeting micelles; cRGD.

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