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

Abstract

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 (ZIF-8) 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 19 F 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.

Polymer-grafted metal–organic frameworks: design, synthesis, and applications

“…16). 61 PFSAM, synthesized using the RAFT mechanism in situ , exhibited excellent hydrophilicity and low-fouling properties, making it a great candidate for bioconjunction and cell uptake. The incorporation of PFSAM increased the aqueous stability of ZIF-8 and imparted efficient delivery to the tumor cells.…”

pH-Responsive Amphiphilic Triblock Fluoropolymers as Assemble Oxygen Nanoshuttles for Enhancing PDT against Hypoxic Tumor

“…In addition to PFCs, fluoropolymers have been widely developed as artificial oxygen carriers for enhancing PDT. Fluoropolymers were known for their excellent self-assembly behaviors in aqueous solutions, allowing for the encapsulation of both hydrophobic and hydrophilic molecules in tailored nanostructures. − Besides self-assembly, the fluoroalkyl chains modified on polymers could overcome the barriers existing in drug delivery and improve tumor accumulation and cell internalization. , Therefore, fluoropolymers have been utilized to enhance PDT by carrying oxygen in photosensitizer-containing nanoparticles. Several amphiphilic fluoropolymers have been developed into nanocapsules or nanomicelles and loaded or conjugated with photosensitizers such as Ce6, IR780, and boron-dipyrromethene (BODIPY) to improve cancer PDT. − Compared to nonfluorinated polymers, these fluoropolymer-based nanocapsules show significantly higher oxygen loading and prolonged oxygen retention.…”

Tunable Zeolitic Imidazolate Framework‐8 Nanoparticles for Biomedical Applications

“…Furthermore, Zn 2+ has excellent antibacterial, anti‐inflammatory and osteogenic capability which means ZIF‐8 exhibits great potential in fields like antibacteria [ 1 ] and bone tissue engineering. [ 2,3 ] More importantly, abundant metal active sites and dynamic microporosity endow ZIF‐8 with the ability to accommodate various guest molecules such as chemotherapeutic agents, [ 4,5 ] photosensitizers, [ 6,7 ] targeting agents, [ 8 ] biomolecules, [ 9,10 ] contrast agent [ 11 ] and so on. Hence, quantities of researches have been done on ZIF‐8 based materials in hot areas like bioimaging and drug delivery system.…”