Pyroelectric Janus nanomotors to promote cell internalization and synergistic tumor therapy

Jie Meng; Kun Wei; Shuang Xie; Zhanlin Zhang; Pan Ran; Peng Zhang; Xiaohong Li

doi:10.1016/j.jconrel.2023.04.007

Pyroelectric Janus nanomotors to promote cell internalization and synergistic tumor therapy

J Control Release. 2023 May:357:342-355. doi: 10.1016/j.jconrel.2023.04.007. Epub 2023 Apr 10.

Authors

Jie Meng¹, Kun Wei¹, Shuang Xie¹, Zhanlin Zhang², Pan Ran², Peng Zhang², Xiaohong Li³

Affiliations

¹ Institute of Biomedical Engineering, College of Medicine, Southwest Jiaotong University, Chengdu 610031, PR China; Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, PR China.
² Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, PR China.
³ Institute of Biomedical Engineering, College of Medicine, Southwest Jiaotong University, Chengdu 610031, PR China; Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, PR China. Electronic address: xhli@swjtu.edu.cn.

PMID: 37030542
DOI: 10.1016/j.jconrel.2023.04.007

Abstract

The tumor diffusion and cell internalization are the major obstacles to improving delivery efficacy of therapeutic agents. External electric fields have shown strong effect on the cell membrane polarization and fluidity, but usually need complicated power management circuits. Herein, in situ generation of microelectric field on nanoparticles (NPs) is proposed to overcome these delivery barriers. Janus tBT@PDA-CPT NPs were developed through partially coating of polydopamine (PDA) caps on pyroelectric tetragonal BaTiO₃ (tBT) NPs and then camptothecin (CPT) conjugation via disulfide linkages. For comparison, cBT@PDA-CPT NPs were prepared from non-pyroelectric cubic BaTiO₃ (cBT) as control. Near-infrared (NIR) illumination on PDA caps of the Janus NPs produces asymmetric thermophoretic force to drive NP motion for tumor accumulation, deep tissue penetration and effective cell interaction. Photothermally created temperature variations on tBT NPs build pyroelectric potentials to selectively change the membrane potential of tumor cells other than normal cells and exhibit a dominated role in enhancing tumor cell internalization and cytotoxicity. The combination index analysis confirms the synergistic effect of pyroelectric dynamic therapy (PEDT), chemotherapy and photothermal therapy (PTT), leading to full inhibition of tumor growth and noticeable extension of animal survival at significant lower CPT doses. The mild PTT/PEDT, the reduced CPT dose and the selective toxicity to tumor cells have achieved favorable treatment safety after tBT@PDA-CPT/NIR treatment. Therefore, in response to the differences in membrane potentials and glutathione levels between tumor and normal cells, we have demonstrated a concise design to achieve thermophoresis-driven motion, pyroelectric potential-enhanced cell internalization and PTT/PEDT/chemotherapy-synergized antitumor treatment.

Keywords: Cell membrane potential; Pyroelectric dynamic therapy; Pyroelectric field; Synergistic effect; Thermophoresis-driven motion.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line, Tumor
Hyperthermia, Induced*
Nanoparticles*
Neoplasms* / drug therapy
Neoplasms* / pathology
Phototherapy

Substances

barium titanate(IV)