#0182

Supramolecular Assembly-Enabled Cancer Theranostics through Concurrent Ferroptosis-Apoptosis

M. Wei¹, L. Tan¹, L. Shang¹

¹Northwestern Polytechnical University, State Key Laboratory of Solidification Processing, School of Materials Science and Engineering, Xi'an, China

Introduction:

Cancer is a tremendous global threat affecting human health nowadays with surging diagnosed cases and mortality rates each year through the worldwide. Currently, clinical treatment methods face numerous challenges including substantial side effects, labeling difficulties, postoperative recurrence and infection. Therefore, early detection and effective treatment are crucial. Ferroptosis is a newly emerged form of cell death characterized by excess reactive oxygen species (ROS) and lipid peroxidation, and the molecular crosstalk between ferroptosis and apoptosis holds great potential as an innovative therapeutic strategy for cancer therapy. Moreover, supramolecular assembly has attracted a broad range of interest in the biological field due to the excellence of designability and controllability, high bioavailability, and drug loading efficiency, as well as dynamic responsive properties. Host-guest interaction mode, one of the most fundamental non-covalent interactions, has been broadly employed to construct supramolecular nanomedicines.

Material and methods:

Fluorescent gold nanoclusters (AuNCs) have emerged as a promising class of nano diagnostic and therapeutic agents due to their precise and controllable structure, excellent light stability, enhanced catalytic activity, superior pharmacokinetics and outstanding biocompatibility. Herein, we use supramolecular macrocycles with unique host-guest properties to regulate the assembly of fluorescent AuNCs, resulting the high-performance supramolecular nanotheranostic materials for enhanced cancer theranostics through concurrent ferroptosis-apoptosis.

Results:

AuNCs act synergistically to generate excessive reactive oxygen species and lipid peroxidation, leading to mitochondrial damage, and ultimately inducing concurrent ferroptosis and apoptosis. Upon further loading into hydrogel microneedles to facilitate their transdermal delivery, the assembly showed superior effects in shortening the treatment span to 3 weeks.