Rolling Circle Amplification-Based Self-Assembly to Form a "GPS-Nanoconveyor" for In Vitro Targeted Imaging and Enhanced Gene/Chemo (CRISPR/DOX) Synergistic Therapy

Biomacromolecules. 2024 Aug 12;25(8):4991-5007. doi: 10.1021/acs.biomac.4c00415. Epub 2024 Aug 1.

Abstract

The GPS-Nanoconveyor (MA-NV@DOX-Cas13a) is a targeted nanoplatform designed for the imaging and gene/chemotherapy synergistic treatment of melanoma. It utilizes rolling circle amplification (RCA) products as a scaffold to construct a DNA "Nanoconveyor" (NV), which incorporates a multivalent aptamer (MA) as a "GPS", encapsulates doxorubicin (DOX) in the transporter, and equips it with CRISPR/Cas13a ribonucleoproteins (Cas13a RNP). Carrying MA enhances the ability to recognize the overexpressed receptor nucleolin on B16 cells, enabling targeted imaging and precise delivery of MA-NV@DOX-Cas13a through receptor-mediated endocytosis. The activation of signal transducer and activator of transcription 3 (STAT3) in cancer cells triggers cis-cleavage of CRISPR/Cas13a, initiating its trans-cleavage function. Additionally, deoxyribonuclease I (DNase I) degrades MA-NV, releasing DOX for intracellular imaging and as a chemotherapeutic agent. Experiments demonstrate the superior capabilities of this versatile nanoplatform for cellular imaging and co-treatment while highlighting the advantages of these nanodrug delivery systems in mitigating DOX side effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / chemistry
  • Antibiotics, Antineoplastic / pharmacology
  • Aptamers, Nucleotide / chemistry
  • CRISPR-Cas Systems*
  • Cell Line, Tumor
  • Doxorubicin* / administration & dosage
  • Doxorubicin* / chemistry
  • Doxorubicin* / pharmacology
  • Humans
  • Mice
  • Nucleic Acid Amplification Techniques / methods

Substances

  • Doxorubicin
  • Aptamers, Nucleotide
  • Antibiotics, Antineoplastic