Metal Phenolic Network‐Integrated Multistage Nanosystem for Enhanced Drug Delivery to Solid Tumors

Abstract

Metal‐phenolic networks (MPNs) are an emerging class of supramolecular surface modifiers with potential use in various fields including drug delivery. Here, the development of a unique MPN‐integrated core‐satellite nanosystem (CS‐NS) is reported. The “core” component of CS‐NS comprises a liposome loaded with EDTA (a metal ion chelator) in the aqueous core and DiR (a near‐infrared photothermal transducer) in the bilayer. The “satellite” component comprises mesoporous silica nanoparticles (MSNs) encapsulating doxorubicin and is coated with a Cu2+‐tannic acid MPN. Liposomes and MSNs self‐assemble into the CS‐NS through adhesion mediated by the MPN. When irradiated with an 808 nm laser, CS‐NS liberated the entrapped EDTA, leading to Cu2+ chelation and subsequent disassembly of the core‐satellite nanostructure. Photo‐conversion from the large assembly to the small constituent particles proceeded within 5 min. Light‐triggered CS‐NS disassembly enhanced the carrier and cargo penetration and accumulation in tumor spheroids in vitro and in orthotopic murine mammary tumors in vivo. CS‐NS is long circulating in the blood and conferred improved survival outcomes to tumor‐bearing mice treated with light, compared to controls. These results demonstrate an MPN‐integrated multistage nanosystem for improved solid tumor treatment.

The Evolution and Future of Targeted Cancer Therapy: From Nanoparticles, Oncolytic Viruses, and Oncolytic Bacteria to the Treatment of Solid Tumors

“…For example, PEGylated, pH-sensitive, folate-coated, liposome-encapsulated Paclitaxel [39,40] contains both a targeting motif and release mechanism providing efficacy against metastatic breast cancer in in vitro studies [39]. Another recent study has suggested a new direction for the field by combining multiple areas of exploration: the newly developed metal-phenolic networks-integrated core-satellite nanosystem is a liposome combining encapsulated EDTA and membrane-bound nearinfrared photothermal transducers [41]. The core satellite component is comprised of mesoporous silica nanoparticles encapsulating doxorubicin while simultaneously coated with a Cu 2+ -tannic acid metal-phenolic network [41].…”

“…Another recent study has suggested a new direction for the field by combining multiple areas of exploration: the newly developed metal-phenolic networks-integrated core-satellite nanosystem is a liposome combining encapsulated EDTA and membrane-bound nearinfrared photothermal transducers [41]. The core satellite component is comprised of mesoporous silica nanoparticles encapsulating doxorubicin while simultaneously coated with a Cu 2+ -tannic acid metal-phenolic network [41]. This combination gave rise to selective payload release upon excitation of the near-infrared photothermal transducer, allowing for more explicit control.…”

“…This combination gave rise to selective payload release upon excitation of the near-infrared photothermal transducer, allowing for more explicit control. Positive outcomes of such an approach are indicated in in vivo studies [41]. This compilation of multiple targeting facets represents a potent future avenue for liposome design.…”

“…The drawbacks of liposomes should be noted-one of which is the spontaneous fusion of liposome membranes, causing decreased drug payload concentration and increasing off-target toxicity [39,41,42]. The most common surface modification, PEGylation, was originally thought to increase circulation time, but additional research has since yielded several conflicting studies, complicating the utilization and implementation [43].…”

“…The most common surface modification, PEGylation, was originally thought to increase circulation time, but additional research has since yielded several conflicting studies, complicating the utilization and implementation [43]. Alternatively, the addition of negatively charged moieties to the surface of liposomes has demonstrated both electrostatic repulsion and stabilization of the liposome, allowing effective drug delivery [41,44]. This avenue for liposome alteration generates a substantial increase in options for NP-hybrid drug delivery with characteristically high retention [41].…”