Near-infrared Light-Triggered Size-Shrinkable theranostic nanomicelles for effective tumor targeting and regression

Int J Pharm. 2024 Jun 10:658:124203. doi: 10.1016/j.ijpharm.2024.124203. Epub 2024 May 4.

Abstract

Most nanomedicines with suitable sizes (normally 100-200 nm) exhibit favorable accumulation in the periphery of tumors but hardly penetrate into deep tumors. Effective penetration of nanomedicines requires smaller sizes (less than 30 nm) to overcome the elevated tumor interstitial fluid pressure. Moreover, integrating an efficient diagnostic agent in the nanomedicines is in high demand for precision theranostics of tumors. To this end, a near-infrared light (NIR) -triggered size-shrinkable micelle system (Fe3O4@AuNFs/DOX-M) coloaded antitumor drug doxorubicin (DOX) and biomodal imaging agent magnetic gold nanoflower (Fe3O4@AuNFs) was developed to achieve efficient theranostic of tumors. Upon the accumulation of Fe3O4@AuNFs/DOX-M in the tumor periphery, a NIR laser was irradiated near the tumor sites, and the loaded Fe3O4@Au NFs could convert the light energy to heat, which triggered the cleavage of DOX-M to the ultra-small micelles (∼5 nm), thus realizing the deep penetration of micelles and on-demand drug release. Moreover, Fe3O4@AuNFs in the micelles could also be used as CT/MRI dual-modal contrast agent to "visualize" the tumor. Up to 92.6 % of tumor inhibition was achieved for the developed Fe3O4@AuNFs/DOX-M under NIR irradiation. This versatile micelle system provided a promising drug carrier platform realizing efficient tumor dual-modal diagnosis and photothermal-chemotherapy integration.

Keywords: Dual-modal imaging; Magnetic gold nanoflower; Photothermal-chemotherapy; Size-shrinkable nanocarriers; Smart drug delivery systems.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Cell Line, Tumor
  • Contrast Media / administration & dosage
  • Contrast Media / chemistry
  • Doxorubicin* / administration & dosage
  • Doxorubicin* / chemistry
  • Drug Carriers / chemistry
  • Drug Delivery Systems / methods
  • Drug Liberation
  • Female
  • Gold* / administration & dosage
  • Gold* / chemistry
  • Humans
  • Infrared Rays*
  • Magnetic Resonance Imaging / methods
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Micelles*
  • Neoplasms / diagnostic imaging
  • Neoplasms / drug therapy
  • Particle Size
  • Theranostic Nanomedicine* / methods

Substances

  • Micelles
  • Doxorubicin
  • Gold
  • Antibiotics, Antineoplastic
  • Contrast Media
  • Drug Carriers