Amorphous Ultra-Small Fe-Based Nanocluster Engineered and ICG Loaded Organo-Mesoporous Silica for GSH Depletion and Photothermal-Chemodynamic Synergistic Therapy.

Intracellular oxidative amplification can effectively destroy tumor cells. Additionally, Fe-mediated Fenton reaction often converts cytoplasm H2 O2 to generate extensive hypertoxic hydroxyl radical (• OH), leading to irreversible mitochondrion damage for tumor celleradication, which is widely famous as tumor chemodynamic therapy (CDT). Unfortunately, intracellular overexpressed glutathione (GSH) always efficiently scavenges • OH, resulting in the significantly reduced CDT effect. To overcome this shortcoming and improve the oxidative stress in cytoplasm, Fe3 O4 ultrasmall nanoparticle encapsulated and ICG loaded organo-mesoporous silica nanovehicles (omSN@Fe-ICG) are constructed to perform both photothermal and GSH depletion to enhance the Fenton-like CDT, by realizing intracellular oxidative stress amplification. After this nanoagents are internalized, the tetrasulfide bonds in the dendritic mesoporous framework can be decomposed with GSH to amplify the toxic ROS neration by selectively converting H2 O2 to hydroxyl radicals through the released Fe-based nanogranules. Furthermore, the NIR laser-induced hyperthermia can further improve the Fenton reaction rate that simultaneously destroyed the mitochondria. As a result, the GSH depletion and photothermal assisted CDT can remarkably improve the tumor eradication efficacy.

Mesoporous Polydopamine-Based Nanovehicles as a Versatile Drug Loading Platform to Enable Tumor-Sufficient Synergistic Therapy.

The combination of photothermal therapy and chemotherapy are developing as a promising clinical strategy but it urgently needs the high exploration of intelligent multifunctional drug delivery nanovectors. In this paper, we used a versatile method to construct mesoporous polydopamine nanovehicles (MPDA) with the dendritic mesopores loaded with a clinical chemotherapeutic drug, Doxorubicin (MPDA@DOX). The monodisperse nanoagents are spherical with a size of ∼160 nm and pore size of approximately 10 nm. MPDA could efficiently delivery DOX with π-π stacking interaction and acts as the potent photothermal agents. Importantly, MPDA@DOX are preferentially internalized by cancerous cells, then bursting drug release and local hyperthermia generation were observed in conditions representative of the cytoplasm in tumor cells that highly synergistic cell killing effect were found under 808 nm laser irradiation. The fluorescent imaging results of human breast tumor bearing murine model evidenced that MPDA delivery platform have excellent tumor precise targeting effect and in vivo tumor ablation experiment further revealed that MPDA@DOX showed markedly eradicated tumor growth capability under laser exposure. Therefore, this work provided a fascinating strategy based on biocompatible MPDA based drug delivery system for malignant tumors eradication via synergistic therapy.

A Novel Yolk-Shell Fe3O4@ Mesoporous Carbon Nanoparticle as an Effective Tumor-Targeting Nanocarrier for Improvement of Chemotherapy and Photothermal Therapy.

Owing to their good stability and high photothermal conversion efficiency, the development of carbon-based nanoparticles has been intensively investigated, while the limitation of unsatisfactory cellular internalization impedes their further clinical application. Herein, we report a novel strategy for fabrication of Fe3O4 yolk-shell mesoporous carbon nanocarriers (Fe3O4@hmC) with monodispersity and uniform size, which presented significantly higher cell membrane adsorption and cellular uptake properties in comparison with common solid silica-supported mesoporous carbon nanoparticles with core-shell structure. Moreover, the MRI performance of this novel Fe-based nanoparticle could facilitate precise tumor diagnosis. More importantly, after DOX loading (Fe3O4@hmC-DOX), owing to synergistic effect of chemo-phototherapy, this therapeutic agent exhibited predominant tumor cell ablation capability under 808 nm NIR laser irradiation, both in vitro and in vivo. Our work has laid a solid foundation for therapeutics with hollowed carbon shell for solid tumor diagnosis and therapy in clinical trials.

Mn(II)-directed dual-photosensitizers co-assemblies for multimodal imaging-guided self-enhanced phototherapy.

Phototherapy has attracted increasing attention in cancer therapy owing to its non-invasive nature, high spatiotemporal selectivity, and negligible side effects. However, a single photosensitizer often exhibits poor photothermal conversion efficiency or insufficient reactive oxygen species (ROS) productivity. Even worse, the ROS can be consumed by tumor overexpressed reductive glutathione, resulting in severely compromised phototherapy. In this paper, we prepared a MnII-coordination driven dual-photosensitizers co-assemblies (IMCP) for imaging-guided self-enhanced PDT/PTT. Specifically, a photothermal agent indocyanine green (ICG), a photodynamic agent chlorin e6 (Ce6), and a transition metal ion (MnII/III) were chosen to synthesize the nanodrug via coordination-driven co-assembly. The as-prepared IMCP exhibited extremely high photosensitizer payload (96 wt%), excellent physiological stability, and outstanding tumor accumulation. Moreover, the existence of MnII not only assists the nanostructure formation but also could competitively coordinate with GSH to minimize the unnecessary ROS consumption, thus improving PDT efficiency. Meanwhile, benefiting from the intrinsic fluorescence, photoacoustic imaging ability of photosensitizers, and the MRI contrast potential of MnII/III, IMCP exhibited superior imaging potential for guiding tumor phototherapy. By changing the excitation wavelength suitably, IMCP could realize the switch between PTT and PDT. In short, the dual-PSs co-assembled nanotheranostic has great potential for multi-modal imaging guided phototherapy.

Light/pH-Triggered Biomimetic Red Blood Cell Membranes Camouflaged Small Molecular Drug Assemblies for Imaging-Guided Combinational Chemo-Photothermal Therapy.

Nanoparticles camouflaged by red blood cell (RBC) membranes have attracted considerable attention owing to reservation of structure of membrane and surface proteins, endowing prominent cell-specific function including biocompatibility, prolonged circulation lifetime, and reduced reticular endothelial system (RES) uptake ability. Considering the drawbacks of carrier-free nanomedicine including the serious drug burst release, poor stability, and lack of immune escape function, herein we developed and fabricated a novel RBC membranes biomimetic combinational therapeutic system by enveloping the small molecular drug coassemblies of 10-hydroxycamptothecin (10-HCPT) and indocyanine green (ICG) in the RBC membranes for prolonged circulation, controlled drug release, and synergistic chemo-photothermal therapy (PTT). The self-reorganized RBCs@ICG-HCPT nanoparticles (NPs) exhibited a diameter of ∼150 nm with core-shell structure, high drug payload (∼92 wt %), and reduced RES uptake function. Taking advantage of the stealth functionality of RBC membranes, RBCs@ICG-HCPT NPs remarkably enhanced the accumulation at the tumor sites by passive targeting followed by cellular endocytosis. Upon the stimuli of near-infrared laser followed by acidic stimulation, RBCs@ICG-HCPT NPs showed exceptional instability by heat-mediated membrane disruption and pH change, thereby triggering the rapid disassembly and accelerated drug release. Consequently, compared with individual treatment, RBCs@ICG-HCPT NPs under dual-stimuli accomplished highly efficient apoptosis in cancer cells and remarkable ablation of tumors by chemo-PTT. This biomimetic nanoplatform based on carrier-free, small molecular drug coassemblies integrating imaging capacity as a promising theranostic system provides potential for cancer diagnosis and combinational therapy.