4.8 Article

Fluoropolymer-MOF Hybrids with Switchable Hydrophilicity for 19F MRI-Monitored Cancer Therapy

Journal

ACS NANO
Volume 17, Issue 9, Pages 8483-8498

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acsnano.3c00694

Keywords

sulfoxide-containing polymers; ZIF-8-PFSAM hybrid nanoparticles; low-fouling; magnetic resonance imaging; theranostics

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This study developed a tumor microenvironment-responsive hybrid theranostic agent by grafting water-soluble, low-fouling fluoropolymers to pH-responsive zeolitic imidazolate framework-8 (ZIF-8) nanoparticles. The nanoparticles showed sensitive in vivo visualization by 19F MRI, prolonged circulation time in the bloodstream, and improved delivery efficiency to tumor tissue. The particles also responded to the acidic tumor microenvironment, leading to degradation and release of zinc ions and encapsulated anticancer drugs.
Cancer theranostics that combines cancer diagnosis and therapy is a promising approach for personalized cancer treatment. However, current theranostic strategies suffer from low imaging sensitivity for visualization and an inability to target the diseased tissue site with high specificity, thus hindering their translation to the clinic. In this study, we have developed a tumor microenvironment-responsive hybrid theranostic agent by grafting water-soluble, low-fouling fluoropolymers to pH-responsive zeolitic imidazolate framework-8 (ZIF8) nanoparticles by surface-initiated RAFT polymerization. The conjugation of the fluoropolymers to ZIF-8 nanoparticles not only allows sensitive in vivo visualization of the nanoparticles by 19F MRI but also significantly prolongs their circulation time in the bloodstream, resulting in improved delivery efficiency to tumor tissue. The ZIF-8-fluoropolymer nanoparticles can respond to the acidic tumor microenvironment, leading to progressive degradation of the nanoparticles and release of zinc ions as well as encapsulated anticancer drugs. The zinc ions released from the ZIF-8 can further coordinate to the fluoropolymers to switch the hydrophilicity and reverse the surface charge of the nanoparticles. This transition in hydrophilicity and surface charge of the polymeric coating can reduce the stealth-like nature of the agent and enhance specific uptake by cancer cells. Hence, these hybrid nanoparticles represent intelligent theranostics with highly sensitive imaging capability, significantly prolonged blood circulation time, greatly improved accumulation within the tumor tissue, and enhanced anticancer therapeutic efficiency.

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