Intrinsic nucleus-targeted ultra-small metal-organic framework for the type I sonodynamic treatment of orthotopic pancreatic carcinoma.

Abstract

BACKGROUND:

Sonodynamic therapy (SDT) strategies exhibit a high tissue penetration depth and can achieve therapeutic efficacy by facilitating the intertumoral release of reactive oxygen species (ROS) with a short lifespan and limited diffusion capabilities. The majority of SDT systems developed to date are of the highly O2-dependent type II variety, limiting their therapeutic utility in pancreatic cancer and other hypoxic solid tumor types.

RESULTS:

Herein, a nucleus-targeted ultra-small Ti-tetrakis(4-carboxyphenyl)porphyrin (TCPP) metal-organic framework (MOF) platform was synthesized and shown to be an effective mediator of SDT. This MOF was capable of generating large quantities of ROS in an oxygen-independent manner in response to low-intensity ultrasound (US) irradiation (0.5 W cm-2), thereby facilitating both type I and type II SDT. This approach thus holds great promise for the treatment of highly hypoxic orthotopic pancreatic carcinoma solid tumors. This Ti-TCPP MOF was able to induce in vitro cellular apoptosis by directly destroying DNA and inducing S phase cell cycle arrest following US irradiation. The prolonged circulation, high intratumoral accumulation, and nucleus-targeting attributes of these MOF preparations significantly also served to significantly inhibit orthotopic pancreatic tumor growth and prolong the survival of tumor-bearing mice following Ti-TCPP + US treatment. Moreover, this Ti-TCPP MOF was almost completely cleared from mice within 7 days of treatment, and no apparent treatment-associated toxicity was observed.

CONCLUSION:

The nucleus-targeted ultra-small Ti-TCPP MOF developed herein represents an effective approach to the enhanced SDT treatment of tumors in response to low-intensity US irradiation.

• Authors: Tao Zhang, Yu Sun, Jing Cao, Jiali Luo, Jing Wang, Zhenqi Jiang, Pintong Huang
• Journal: Journal of nanobiotechnology (J Nanobiotechnology) Vol. 19 Issue 1 Pg. 315 (Oct 12 2021) ISSN: 1477-3155 [Electronic] England
• PMID: 34641905 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s).

Chemical References

• Metal-Organic Frameworks

Topics

• Animals
• Apoptosis (drug effects, radiation effects)
• Cell Hypoxia (drug effects, radiation effects)
• Cell Line, Tumor
• Female
• Humans
• Metal-Organic Frameworks (pharmacology)
• Mice
• Mice, Nude
• Neoplasms, Experimental (therapy)
• Pancreatic Neoplasms (therapy)
• Ultrasonic Therapy