Steerable Microneedles Enabling Deep Delivery of Photosensitizers and CRISPR/Cas9 Systems for Effective Combination Cancer Therapy

Tong Wang, Gang Chen, Shuangshuang Zhang, Dazhao Li, Guanjun Wei, Xiaomei Zhao, Yang Liu*, Dawei Ding*, Xuenong Zhang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Although gene therapy has shown prospects in treating triple-negative breast cancer, it is insufficient to treat such a malignant tumor. Herein, nanoparticles (NPs)-embedded dissolving microneedles (IR780-PL/pFBXO44@MNs) with steerable and flectional property were developed to achieve the codelivery of FBXO44-targeted CRISPR/Cas9 plasmids (pFBXO44) and hydrophobic photosensitizers. For improved NP penetration in tumor tissue, collagenase@MNs were preapplied to degrade the tumor matrix. Under light irradiation, IR780 exhibited remarkable phototherapy, while the escape efficiency of NPs from lysosomes was improved. pFBXO44 was subsequently released in tumor cell cytoplasm via reducing the disulfide bonds of NPs, which could specifically knock out the FBXO44 gene to inhibit the migration and invasion of tumor cells. As a result, tumor cells were eradicated, and lung metastasis was effectively suppressed. This micelle-incorporated microneedle platform broadens the potential of combining gene editing and photo synergistic cancer therapy.

Original languageEnglish
Pages (from-to)7990-7999
Number of pages10
JournalNano Letters
Volume23
Issue number17
DOIs
Publication statusPublished - 13 Sept 2023
Externally publishedYes

Keywords

  • CRISPR/Cas9
  • Dissolving microneedles
  • Metastasis
  • Penetration
  • Phototherapy
  • Synergistic cancer therapy

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