Photodynamic therapy (PDT) as a noninvasive therapy mode has attracted considerable attention in the field of oncotherapy. However, the PDT efficacy is restricted either by the tumor hypoxia environment or the inherent properties of photosensitizers (PSs) including bad water solution, photobleaching, and easy aggregation. Herein, we designed and synthesized a new two-dimensional (2D) metal−organic framework, Sm-tetrakis(4-carboxyphenyl)porphyrin (TCPP) nanosheets, by assembling transition metal ions (Sm 3+ ) and PSs (TCPP), on which the catalase (CAT)-mimicking platinum nanozymes were then in situ grown for sufficient oxygen supply during PDT. The prepared Sm-TCPP with nanoplate morphology (∼100 nm in diameter) and ultrathin thickness (<10 nm) showed significantly enhanced 1 O 2 generation capacity due to the improved physicochemical properties and the enhanced intersystem crossing from heavy Sm nodes. More importantly, the CAT-mimicking Pt nanozyme on the Sm-TCPP nanosheets could effectively convert over-expressed H 2 O 2 in the tumor microenvironment into O 2 to relieve tumor hypoxia. Further, the triphenylphosphine (TPP) molecule was introduced to Sm-TCPP-Pt to develop a mitochondrion-targeting and O 2 self-supply PDT system. The in vitro and in vivo experimental results based on the MCF-7 breast cancer model revealed that Sm-TCPP-Pt/TPP could relieve tumor hypoxia and the generated reactive oxygen species nearby intracellular mitochondria significantly induced cell apoptosis. This study offers an engineering strategy to integrate 2D PS-based metal−organic frameworks and nanozymes into a nanoplatform to surmount the pitfalls of traditional PDT.
Herein, a biocompatible 2D metal-organic frameworks (Cu-TCPP(Fe)) based on TCPP(M) (TCPP = tetrakis (4-carboxyphenyl) porphyrin, M = Fe) and copper ion were synthesized as a novel drug carrier. Sequentially, the cisplatin was loaded on the merge of carboxyl-rich Cu-TCPP(Fe) through forming favorable carboxyl-drug interactions. The prepared Pt/Cu-TCPP(Fe) showed highly enhanced cytotoxicity than that of free cisplatin in human pulmonary carcinoma A549 cells, whereas inverse inhibitory effects were observed in human normal BEAS-2B cells. Further, the mechanism of action about the desirable results was also elaborated. Our study highlighted the potential synergies between the nanocarrier and the anticancer drugs.
Until
now, ferroptotic therapeutic strategies remain simple, although
ferroptosis has aroused extensive interest owing to its escape from
the biocarriers of conventional therapeutic modalities. Herein, we
construct a photothermal (PT)- and autophagy-enhanced ferroptotic
therapeutic modality based on MnO2@HMCu2–x
S nanocomposites (HMCMs) for efficient tumor ablation.
The HMCMs possess PT-enhanced glutathione (GSH) depletion capability,
thereby inducing PT-enhanced ferroptosis via the reinforced inactivation
of glutathione peroxidase 4 (GPX4). Thereafter, the GSH-responsed
Mn2+ release could generate reactive oxygen species (ROS)
by a Fenton-like reaction to reinforce the intracellular oxidative
stress for the lipid hydroperoxide (LPO) accumulation in ferroptosis.
Additionally, an autophagy promotor rapamycin (Rapa) was loaded into
HMCM for sensitizing cells to ferroptosis due to the indispensable
role of autophagy in the ferroptosis process. The in vitro and in
vivo data demonstrated that the HMCM exhibited superior anticancer
effect in human breast cancer models and that the combined therapeutic
system afforded the next generation of ferroptotic therapy for combatting
malignant tumors.
Highly toxic reactive oxygen species levels were enhanced via iron oxide core–shell mesoporous silica nanocarrier-mediated Fenton reactions for cancer therapy.
Through a facile-operating ultrasonic force-assisted liquid exfoliation technology, the single-layered two-dimensional (2D) [Co(CNS)(pyz)] (pyz = pyrazine) nanosheets, with a thickness of sub-1.0 nm, have been prepared from the bulk precursors. The atomically thickness and the presence of abundant sulfur atoms with high electronegativity arrayed on the double surfaces of the sheets are making this kind of 2D MOF (metal-organic framework) nanosheets highly sensitive to intermolecular interactions. As a result, it can be well dispersed in all kinds of solvents to give a stable colloidal suspension that can be maintained for at least one month, accompanied by significant solvatochromic behavior and various optical properties, which thus have shown the potential to be practically applicated as in situ visual test paper for solvent identification and solvent polarity measurements. More importantly, combined with a smartphone, this kind of 2D-MOF nanosheets can be developed into in situ visual test paper to identify isomers and determine the polarity of mixed solvents quantitatively and qualitatively, suggesting the promising application of a portable, economical, and in situ visual test strategy in real world.
A tumor microenvironment is distinct from normal tissue cells in characteristic physiochemical conditions, based on which we can design tumor-specific therapy modalities.
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