Oncocyte Membrane-Camouflaged Multi-Stimuli-Responsive Nanohybrids for Synergistic Amplification of Tumor Oxidative Stresses and Photothermal Enhanced Cancer Therapy.

The combination of various therapeutic modalities has received considerable attention for improving antitumor performance. Herein, an innovative nanohybrid, namely CaO2@FePt-DOX@PDA@CM (CFDPM), was developed for synergistic chemotherapy/chemodynamic therapy/Ca2+ overloading-mediated amplification of tumor oxidative stress and photothermal enhanced cancer therapy. Camouflage of the 4T1 cell membrane enabled CFDPM to escape the immune surveillance and accumulate in the tumor tissue. Ca2+, released from CaO2, could lead to mitochondrial dysfunction and facilitate the production of reactive oxygen species to amplify intracellular oxidative stress. Meanwhile, the increase of H2O2 concentration could enhance the efficiency of the chemodynamic therapy (CDT). Moreover, the hypoxic condition could be alleviated remarkably, which is attributed to the sufficient O2 supply by CaO2, resulting in the suppression of drug resistance and promotion of the chemotherapeutic effect. The nanohybrids involving Ca2+ overloading/CDT/chemotherapy could synergistically amplify the tumor oxidative stresses and remarkably aggravate the death of cancer cells. Significantly, the excellent photothermal conversion performance of CFDPM could further promote the tumoricidal effect. The in vitro and in vivo studies revealed that CFDPM could effectively advance the therapeutic efficiency via the cooperation of various therapeutic modalities to optimize their individual virtue, which would open a valuable avenue for effective cancer treatment.

A novel multifunctional FePt/BP nanoplatform for synergistic photothermal/photodynamic/chemodynamic cancer therapies and photothermally-enhanced immunotherapy.

A new multi-modal therapy agent, FePt/BP-PEI-FA nanoplatform, with FePt nanoparticles (FePt NPs) loaded onto ultrathin black phosphorus nanosheets (BPNs), has been constructed to enhance synergistic photothermal therapy (PTT), photodynamic therapy (PDT), and chemodynamic therapy (CDT) that target primary tumors. In this work, BPNs exhibit excellent photothermal and photodynamic behaviors under different wavelength laser irradiation. After polyethylenimine (PEI) modification, FePt NPs with sizes of 3-4 nm are uniformly attached onto the surface of modified BPNs via electrostatic adsorption. FePt NPs, as a ferroptosis agent, can transform endogenous H2O2 into reactive oxygen species (ROS) through the Fenton reaction, ultimately inducing cell death. Based on magnetic resonance imaging (MR) and thermal imaging, the as-prepared FePt/BP-PEI-FA NCs can inhibit tumor growth by achieving synergistic therapies. More significantly, combined with cytotoxic T lymphocyte-associated protein 4 (CTLA-4) checkpoint blockade, FePt/BP-PEI-FA NC-induced PTT can control both primary and untreated distant tumors' growth. Therefore, FePt/BP-PEI-FA NCs is a potential multifunctional nanoagent for effective anti-tumor applications.

A novel theranostic nano-platform (PB@FePt-HA-g-PEG) for tumor chemodynamic-photothermal co-therapy and triple-modal imaging (MR/CT/PI) diagnosis.

The construction of multi-functional oncotherapy nano-platforms combining diagnosis and therapy remains a tough challenge. Prussian blue nano-cubes with optimized particle size were applied as photothermal agents and loaded with FePt NPs, effective ferroptosis agents, on the surface via an in situ reduction strategy. To attain the goal of precise medicine, hyaluronic acid was wrapped around the surface of the nanocomposites (PB@FePt NCs) for highly specific recognition of tumor cells. Finally, we successfully designed and fabricated a nano-agent (PB@FePt-HA-g-PEG NCs) to serve as a versatile nano-platform with both highly specific targeting ability for chemodynamic-photothermal co-therapy and triple-modal imaging (magnetic resonance/computed tomography/photothermal imaging) capability. Via intravenous injection, the as-constructed oncotherapy nano-platform could effectively ablate 4T1 tumor xenografts with excellent biocompatibility for chemodynamic-photothermal co-therapy. In this study we conducted a reasonable exploration to design multi-functional oncotherapy nano-platforms combining multiplexed imaging diagnosis and high therapeutic performance, which provides an innovative paradigm for precision cancer treatment.

Tumor microenvironment responsive FePt/MoS2 nanocomposites with chemotherapy and photothermal therapy for enhancing cancer immunotherapy.

The metastasis and recurrence of tumors are the main reasons for cancer death. In this work, a promising therapy for tumor treatment that can eliminate primary tumors and prevent tumor relapses is introduced by combining chemotherapy, photothermal therapy (PTT) and immunotherapy. Multifunctional FePt/MoS2-FA nanocomposites (FPMF NCs) were obtained via anchoring FePt nanoparticles and folic acid (FA) on MoS2 nanosheets. As an efficient ferroptosis agent, FePt nanoparticles could catalyze the Fenton reaction to produce the reactive oxygen species (ROS). Through the highly effective photothermal conversion of MoS2 nanosheets, the primary tumor cells could be ablated by photothermal therapy (PTT). Moreover, the metastatic tumors were eliminated effectively with the help of oligodeoxynucleotides containing cytosine-guanine (CpG ODNs) combined with systemic checkpoint blockade therapy using an anti-CTLA4 antibody. Even more intriguingly, a strong immunological memory effect was obtained by this synergistic therapy. Taking all these results into consideration, we anticipate that the photo-chemo-immunotherapy strategies show great promise toward the development of a multifunctional platform for anticancer therapeutic applications.