7 research outputs found
Rational Design of Multi-Stimuli-Responsive Nanoparticles for Precise Cancer Therapy
Stimuli-responsive nanoparticles
with target capacity are of great
interest in drug delivery for cancer therapy. However, the challenge
is to achieve highly smart release with precise spatiotemporal control
for cancer therapy. Herein, we report the preparation and properties
of multi-stimuli-responsive nanoparticles through the co-assembly
of a 3-arm star quaterpolymer with a near-infrared (NIR) photothermal
agent and chemotherapeutic compound. The nanoparticles can exhibit
NIR light/pH/reduction–responsive drug release and intracellular
drug translocation in cancer cells, which further integrate photoinduced
hyperthermia for synergistic anticancer efficiency, thereby leading
to tumor ablation without tumor regrowth. Thus, this rational design
of nanoparticles with multiple responsiveness represents a versatile
strategy to provide smart drug delivery paradigms for cancer therapy
Light-Responsive Nanoparticles for Highly Efficient Cytoplasmic Delivery of Anticancer Agents
Stimuli-responsive
nanostructures have shown great promise for
intracellular delivery of anticancer compounds. A critical challenge
remains in the exploration of stimuli-responsive nanoparticles for
fast cytoplasmic delivery. Herein, near-infrared (NIR) light-responsive
nanoparticles were rationally designed to generate highly efficient
cytoplasmic delivery of anticancer agents for synergistic thermo-chemotherapy.
The drug-loaded polymeric nanoparticles of selenium-inserted copolymer
(I/D-Se-NPs) were rapidly dissociated in several minutes through reactive
oxygen species (ROS)-mediated selenium oxidation upon NIR light exposure,
and this irreversible dissociation of I/D-Se-NPs upon such a short
irradiation promoted continuous drug release. Moreover, I/D-Se-NPs
facilitated cytoplasmic drug translocation through ROS-triggered lysosomal
disruption and thus resulted in highly preferable distribution to
the nucleus even in 5 min postirradiation, which was further integrated
with light-triggered hyperthermia for achieving synergistic tumor
ablation without tumor regrowth
Dually pH/Reduction-Responsive Vesicles for Ultrahigh-Contrast Fluorescence Imaging and Thermo-Chemotherapy-Synergized Tumor Ablation
Smart nanocarriers are of particular interest as nanoscale vehicles of imaging and therapeutic agents in the field of theranostics. Herein, we report dually pH/reduction-responsive terpolymeric vesicles with monodispersive size distribution, which are constructed by assembling acetal- and disulfide-functionalized star terpolymer with near-infrared cyanine dye and anticancer drug. The vesicular nanostructure exhibits multiple theranostic features including on-demand drug releases responding to pH/reduction stimuli, enhanced photothermal conversion efficiency of cyanine dye, and efficient drug translocation from lysosomes to cytoplasma, as well as preferable cellular uptakes and biodistribution. These multiple theranostic features result in ultrahigh-contrast fluorescence imaging and thermo-chemotherapy-synergized tumor ablation. The dually stimuli-responsive vesicles represent a versatile theranostic approach for enhanced cancer imaging and therapy
Multipronged Design of Light-Triggered Nanoparticles To Overcome Cisplatin Resistance for Efficient Ablation of Resistant Tumor
Chemotherapeutic drugs frequently encounter multiple drug resistance in the field of cancer therapy. The strategy has been explored with limited success for the ablation of drug-resistant tumor <i>via</i> intravenous administration. In this work, the rationally designed light-triggered nanoparticles with multipronged physicochemical and biological features are developed to overcome cisplatin resistance <i>via</i> the assembly of Pt(IV) prodrug and cyanine dye (Cypate) within the copolymer for efficient ablation of cisplatin-resistant tumor. The micelles exhibit good photostability, sustained release, preferable tumor accumulation, and enhanced cellular uptake with reduced efflux on both A549 cells and resistant A549R cells. Moreover, near-infrared light not only triggers the photothermal effect of the micelles for remarkable photothermal cytotoxicity, but also leads to the intracellular translocation of the micelles and reduction-activable Pt(IV) prodrug into cytoplasm through the lysosomal disruption, as well as the remarkable inhibition on the expression of a drug-efflux transporter, multidrug resistance-associated protein 1 (MRP1) for further reversal of drug resistance of A549R cells. Consequently, the multipronged effects of light-triggered micelles cause synergistic cytotoxicity against both A549 cells and A549R cells, and thus efficient ablation of cisplatin-resistant tumor without regrowth. The multipronged features of light-triggered micelles represent a versatile synergistic approach for the ablation of resistant tumor in the field of cancer therapy
MnO<sub>2</sub>‑Based Nanoplatform Serves as Drug Vehicle and MRI Contrast Agent for Cancer Theranostics
Multidrug
resistance (MDR) greatly impedes the therapeutic efficacy of chemotherapeutic
agents. Overexpression of ATP-binding cassette (ABC) transporters,
such as P-gp, on the surface of tumor cells is a major mechanism in
MDR. In this study, we fabricated manganese dioxide (MnO<sub>2</sub>)/doxorubicin (DOX)-loaded albumin nanoparticles (BMDN) for magnetic
resonance imaging and reversing MDR in resistant tumor. BMDN facilitated
the delivery of DOX into MDR tumor cells through their MDR reversal
effects including enhanced cellular uptake, reduced drug efflux, and
decreased hypoxic tumor microenvironment. BMDN also acted as an effective
MRI contrast agent, thereby causing good in vitro and in vivo <i>T</i><sub>1</sub>-weighted imaging
Size-Dependent Ag<sub>2</sub>S Nanodots for Second Near-Infrared Fluorescence/Photoacoustics Imaging and Simultaneous Photothermal Therapy
Ag<sub>2</sub>S nanoparticles
are increasingly important in biomedicine,
such as in cancer imaging. However, there has been only limited success
in the exploration of theranostic Ag<sub>2</sub>S nanoparticles for
photoinduced cancer imaging and simultaneous therapy. Here we report
size-dependent Ag<sub>2</sub>S nanodots (NDs) with well-defined nanostructure
as a theranostic agent for multimodal imaging and simultaneous photothermal
therapy. The NDs are precisely synthesized through carefully controlled
growth of Ag<sub>2</sub>S in hollow human serum albumin nanocages.
These NDs produce effective fluorescence in second near-infrared (NIR-II)
region, distinct photoacoustic intensity, and good photothermal conversion
in a size-dependent manner under light irradiation, thereby generating
sufficient <i>in vivo</i> fluorescence and photoacoustic
signals as well as potent hyperthermia at tumors. Moreover, Ag<sub>2</sub>S NDs possess ideal resistance to photobleaching, effective
cellular uptake, preferable tumor accumulation, and <i>in vivo</i> elimination, thus facilitating NIR-II fluorescence/photoacoustics
imaging with both ultrasensitivity and microscopic spatial resolution
and simultaneous photothermal tumor ablation. These findings provide
insight into the clinical potential of Ag<sub>2</sub>S nanodots for
cancer theranostics
Bifunctional Tellurium Nanodots for Photo-Induced Synergistic Cancer Therapy
Elemental
tellurium (Te) nanoparticles are increasingly important
in a variety of applications such as thermoelectricity, photoconductivity,
and piezoelectricity. However, they have been explored with limited
success in their biomedical use, and thus a tremendous challenge still
exists in the exploration of Te nanoparticles that can treat tumors
as an effective anticancer agent. Here, we introduce bifunctional
Te nanodots with well-defined nanostructure as an effective anticancer
agent for photo-induced synergistic cancer therapy with tumor ablation,
which is accomplished using hollow albumin nanocages as a nanoreactor.
Under near-infrared light irradiation, Te nanodots can produce effective
photothermal conversion, as well as highly reactive oxygen species
such as •O<sub>2</sub><sup>–</sup> and dismutated •OH <i>via</i> a type-I mechanism through direct electron transfer,
thereby triggering the potent <i>in vivo</i> hyperthermia
and simultaneous intracellular reactive oxygen species at tumors.
Moreover, Te nanodots possess perfect resistance to photobleaching,
effective cytoplasmic translocation, preferable tumor accumulation,
as well as <i>in vivo</i> renal elimination, promoting severe
photo-induced cell damage and subsequent synergy between photothermal
and photodynamic treatments for tumor ablation. These findings provide
the insight of elemental Te nanodots for biomedical research