Supramolecular nanomedicines, which use supramolecular design to improve the precision and effectiveness of pharmaceutical practice and optimize pharmacokinetic profiles, have gathered momentum to battle cancer and other incurable diseases, for which traditional small‐molecular and macromolecular drugs are less effective. However, the lack of clinical approval of supramolecular assembly‐based medicine underscores the challenges facing this field. A 2D nanodisc‐based supramolecular structure is formed by a non‐ionic heptamethine cyanine (Cy7) dye, which generates fluorescence self‐quenching but unique photothermal and photoacoustic properties. These Cy7‐based supramolecular nanodiscs exhibit passive tumor‐targeting properties to not only visualize the tumor by near‐infrared fluorescence imaging and photoacoustic tomography but also induce photothermal tumor ablation under irradiation. Due to the nature of organic small molecule, they induce undetectable acute toxicity in mice and can be eliminated by the liver without extrahepatic metabolism. These findings suggest that the self‐assembling cyanine discs represent a new paradigm in drug delivery as single‐component supramolecular nanomedicines that are self‐delivering and self‐formulating, and provide a platform technology for synergistic clinical cancer imaging and therapy.
Organic small-molecule-based
photothermal agents such as cyanine
dyes have received increasing attention in developing novel cancer
therapies with potential clinical utility but suffer from poor stability,
low photothermal efficiency, and limited accumulation at tumor sites
in molecular forms. Self-assembly of small-molecule dyes into supramolecular
assemblies may address these concerns by controlling the molecular
organization of dye monomers to form structures of a higher order.
Among them, H-aggregates of dyes favor face-to-face contacts with
strongly overlapping areas, which always have a negative connotation
to exhibit low or no fluorescence in most cases but may emanate energy
in nonradiative forms such as heat for photothermal cancer therapy
applications. Here, the synergistic self-assembly of cyanine dyes
into H-aggregates is developed as a new supramolecular strategy to
fabricate small-molecule-based photothermal nanomaterials. Compared
to the free cyanine dyes, the H-aggregates assembled from pyrene or
tetraphenylethene (TPE) conjugating cyanine exhibit the expected absorption
spectral blue shift and fluorescence self-quenching but unique photothermal
properties. Remarkably, the obtained H-aggregates are saucer-shaped
nanoparticles that exhibit passive tumor-targeting properties to induce
imaging-guided photothermal tumor ablation under irradiation. This
supramolecular strategy presented herein may open up new opportunities
for constructing next-generation small-molecule-based self-assembly
nanomaterials for PTT cancer therapy in clinics.
A water-soluble two-dimensional supramolecular organic framework (2D SOF) with AIE effect was prepared and exhibited excellent live-cell imaging behavior.
Developing high-performance noninvasive probe for precise cancer theranostics is very challenging but urgently demanded. Herein a novel Au nanoclusters (NCs)-based probe is designed for cancer theranostic via ligand engineering by...
Enzyme-responsive polypeptide vesicles
have attracted considerable
attention for precision theranostics because of their biocompatibility,
biodegradability, and unique secondary conformation transition triggered
by the catalytic actions of enzymes. These promising potentials of
polypeptide vesicles could be limited in a drug delivery system by
the very slow enzyme diffusion rate into vesicles that could reduce
the efficacy of the drug. On the other hand, stimuli-responsive polymeric
vesicles that respond to stimuli can undergo microstructure destruction
for the burst release of drugs, which would penetrate through the
membrane of dead cells and the tumor extracellular matrix, inducing
acute toxicity to neighboring cells. Here, we designed amphiphilic
PEG–polypeptide copolymers containing esterase-labile carbamate-caged
primary amines. It was found that the diblock can self-assemble into
vesicular structures. Esterase-triggered self-immolative decaging
reactions could quickly release the primary amine moiety of monomers
that can undergo an amidation reaction for transition of the bilayer
of vesicles from hydrophobic to partially hydrophilic. This esterase-responsive
process retains the nanostructure of vesicles but permeabilizes the
vesicle membrane, which can afford the sustained release of encapsulating
drugs. These esterase-responsive polypeptide vesicles mediate selective
cytotoxicity in cancer cells with high esterase expression over normal
fibroblasts with low esterase, enabling the potent anticancer chemotherapy
with minimized side effects.
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