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.

The multi-therapy modality is based on the combination and synergy of multiple single treatment modalities and materials chemistry.

A tumor microenvironment is distinct from normal tissue cells in characteristic physiochemical conditions, based on which we can design tumor-specific therapy modalities.

No abstract

Combination therapy with multiple drugs through a multi-pronged assault as a strategy to combat cisplatin resistance shows great potential in biochemical therapy for cancer. However, inherent issues such as low drug loading and the poor synergistic effects of multiple drugs partially limit the further application of combination therapy. Here, we synthesized a new compound, ART-Chol, by coupling artemisinin and cholesterol as a base material combined with cyclic (Arg-Gly-Asp-D-Phe-Lys)]-poly(ethylene glycol) distearoylphosphatidylcholine (cRGD-PEG-DSPE) and phospholipids to form a magnetic liposome cRGD-AFePt@NPs encapsulating superparamagnetic ferric oxide nanoparticles and cisplatin for achieving high drug loading and a better synergistic effect. The cRGD-AFePt@NPs could be effectively internalized and responsively release loading cargos under alternating magnetic field irradiation due to local hyperthermia generated from magnetic nanoparticles by hysteresis loss and Neél relaxation. The generated Fe 2+ /Fe 3+ from Fe 3 O 4 NPs in the acid lysosomes motivated cisplatin and catalyzed the Fe-dependent anticancer drug artemisinin (ART) to generate highly toxic ROS through the Fenton reaction, which greatly enhances the anticancer effect of cisplatin with minimized side effects. In vitro cytotoxicity tests demonstrated that the cRGD-AFePt@NPs exhibited a 15.17-fold lower IC 50 value of free cisplatin (IC 50 = 32.47 μM) against A549/R cells. Further flow-cytometry tests also showed obviously increased intracellular ROS generation and cell apoptosis rates. We highlight the potential for Fe 2+ /Fe 3+ -mediated combination therapy of cisplatin and ART for circumventing cisplatin drug resistance.

Surmounting the restriction issues of nitric oxide (NO) delivery to realize their precious on-demand release is highly beneficial for the widespread deployment of gas therapy for application in biomedicine. Herein, by employing core−shell structure Au@SiO 2 nanomaterials with high photothermal performance, a novel strategy was proposed by integrating photothermal conversion nanomaterials and heat-triggered NO donors (RSNO) into a nanoplatform, which achieved photothermal therapy (PTT)enhanced NO gas therapy under near-infrared (NIR) radiation. Specifically, 2-phenylethynesulfonamide (PES), an inhibitor of heat shock protein 70 (HSP-70), was loaded into the NO nanogenerators to realize effective low-temperature (∼45 °C) PTT. The obtained results showed that the near-infrared radiation (NIR) mediated mild PTT and gas therapy by releasing NO showed a substantially improved synergistic effect based on in vitro and in vivo results in breast cancer (MCF-7) models. Our study points out a strategy to realize mild photothermal therapy by inhibiting the expression of HSP-70 and simultaneously providing an avenue to achieve controllable release of NO. More important, this research highlights the great potential of multifunctional therapeutic agents in the synergistic treatment of cancer.