Rational design of pH-responsive nano-delivery system with improved biocompatibility and targeting ability from cellulose nanocrystals via surface polymerization for intracellular drug delivery

  • Int J Biol Macromol. 2024 Nov;281(Pt 4):136435. doi: 10.1016/j.ijbiomac.2024.136435.
Ziqi Li  1 ,  Xi Wang  2 ,  Weimin Wan  2 ,  Na Zhang  2 ,  Limeng Zhang  2 ,  Xiaoye Wang  3 ,  Kui Lin  4 ,  Jian Yang  2 ,  Jia Hao  2 ,  Fei Tian  5
Affiliations
  • 1. National Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China; Haihe Laboratory of Modern Chinese Medicine, Tianjin 301617, PR China; Department of Pharmacy, Jiangxi Maternal and Child Health Hospital, Jiangxi 330103, PR China.
  • 2. National Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China; Haihe Laboratory of Modern Chinese Medicine, Tianjin 301617, PR China.
  • 3. Department of Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin 300052, China.
  • 4. Analytical Instrumentation Centre, Tianjin University, Tianjin 300072, PR China.
  • 5. National Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China; Haihe Laboratory of Modern Chinese Medicine, Tianjin 301617, PR China. Electronic address: [email protected].
PMID: 39414191 DOI: 10.1016/j.ijbiomac.2024.136435
Abstract

Cellulose nanocrystals (CNCs), derived from diverse sources and distinguished by their inherent biodegradability, excellent biocompatibility, and facile cellular engulfment due to their rod-like structure, hold great promise as carriers for the development of nano-delivery systems. In this work, highly efficient rod-like CNCs were employed as substrates for grafting glycidyl onto their surfaces through ring-opening polymerization, forming hyperbranched Polymers with superior cell uptake properties. Subsequently, 4-vinylbenzeneboronic acid (VB) and poly (ethylene glycol) methyl ether methacrylate (PEGMA) were employed as monomers in the polymerization process to fabricate a pH-responsive targeted nano-delivery system, denoted as CNCs-VB-PEGMA, via single electron transfer reactive radical polymerization (SET-LRP) reaction. The CNCs-VB-PEGMA was successfully prepared and used for the loading of curcumin (Cur) to form a pH-responsive nano-delivery system (CNCs-VB-PEGMA-Cur), and the loading rate of Cur was as high as 70.0 %. Studies showed that this drug delivery system could actively targeting liver Cancer cells with the 2D cells model and 3D tumor microsphere model, showing efficient liver Cancer cell-killing ability. Collectively, the CNCs-VB-PEGMA drug delivery system has potential applications in liver Cancer therapy as an actively targeting and pH-responsive drug delivery system.

Keywords
Active targeting delivery; Cellulose nanocrystals; Hyperbranched polymer; SET-LRP; pH-responsive.
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