Self-assembled tocopherol-albumin nanoparticles with full biocompatibility for chemo-photothermal therapy against breast cancer

Background:: The combination of photothermal therapy (PTT) and chemotherapy has proven to be a promising strategy for cancer treatment. Various nanomaterials have shown great potential in combination therapy, including gold, graphene oxide, iron oxide, and other nanoparticles. However, their undefinable toxicity in vivo greatly slowed down their development for clinical applications. Objective: The present work aimed to develop a multifunctional nanoparticle for chemo-photothermal therapy composed of acknowledged biocompatible materials. Methods: A novel biocompatible nanoparticle (HIT-NPs) was self-assembled through the intrinsic interaction between D-α-tocopherol Succinate (TOS), human serum albumin (HSA) and indocyanine green (ICG). Doxorubicin (DOX) was then loaded due to the ion pairing between DOX and TOS. The feasibility of combined chemo-photothermal therapy induced by DOX-loaded HIT-NPs was carefully evaluated. Results: In vitro, HIT-NPs showed no cytotoxicity on human normal liver cells (HL-7702 cells) but obvious killing effects murine breast cancer cells (4T1 cells). The combined chemo-photothermal therapeutic effect on 4T1 cells was successfully obtained. DOX-loaded HIT-NPs could effectively accumulate in 4T1 subcutaneous tumors after intravenous injection, and the tumor temperature rapidly increased under laser exposure, indicating the feasibility of PTT in vivo. Conclusion: The self-assembled HIT-NPs could provide a promising platform for combined chemo-photothermal cancer therapy with full biocompatibility.

Multifunctional nanoparticle-mediated SHARP1 knockdown in MLL-AF6 acute myeloid leukemia

Acute myeloid leukemia (AML) has an extremely poor prognosis and high relapse and fatality rates. We targeted SHARP1 using multifunctional small interfering RNA (siRNA) and bortezomib (BTZ)-loaded cRGD-guided PEGylated cationic liposomal nanoparticles to monitor their antileukemic activity in MLL-AF6 AML cells. Efficient siRNA/BTZ co-delivery by the nanoparticles significantly inhibited cell viability, decreasing clonogenic growth of AML cells and stimulating robust apoptosis. We hypothesized that SHARP1 downregulation induced nonfunctional MLL-AF6, DOT1L, MEN1, and LEDGF fusion protein accumulation, preventing MLL-AF complex formation and downregulating RAS-GTP and Bcl-2, consequently triggering autophagy and apoptosis. The BTZ combination substantially augmented therapeutic synergy leading to enhanced autophagic and apoptotic events. Our findings demonstrate a state-of-the-art biodegradable nanoplatform for siRNA/BTZ co-delivery with targeted SHARP1 knockdown, demonstrating a potential therapeutic option for MLL-AF6 AML.

Polypyrrole-Coated Magnetite Vortex Nanoring for Hyperthermia-Boosted Photothermal/Magnetothermal Tumor Ablation Under Photoacoustic/Magnetic Resonance Guidance

Photothermal/magnetothermal-based hyperthermia cancer therapy techniques have been widely investigated, and associated nanotechnology-assisted treatments have shown promising clinical potentials. However, each method has some limitations, which have impeded extensive applications. For example, the penetration ability of the photothermal is not satisfactory, while the heating efficiency of the magnetothermal is very poor. In this study, a novel magnetite vortex nanoring nanoparticle-coated with polypyrrole (denoted as nanoring Fe3O4@PPy-PEG) was first synthesized and well-characterized. By combining photothermal and magnetothermal effects, the performance of the dual-enhanced hyperthermia was significantly improved, and was thoroughly examined in this study. Benefiting from the magnetite vortex nanoring and polypyrrole, Fe3O4@PPy-PEG showed excellent hyperthermia effects (SAR = 1,648 Wg–1) when simultaneously exposed to the alternating magnetic field (300 kHz, 45 A) and near-infrared (808 nm, 1 W cm–2) laser. What is more, nanoring Fe3O4@PPy-PEG showed a much faster heating rate, which can further augment the antitumor effect by incurring vascular disorder. Besides, Fe3O4@PPy-PEG exhibited a high transverse relaxation rate [60.61 mM–1 S–1 (Fe)] at a very low B0 field (0.35 T) and good photoacoustic effect. We believe that the results obtained herein can significantly promote the development of multifunctional nanoparticle-mediated magnetic and photo induced efficient hyperthermia therapy.

Multifunctional superparamagnetic nanoparticles with a fluorescent silica shell for the in vitro study of bio-nano interactions at the subcellular scale

A multifunctional nanoparticle was developed to study the bio-nano interactions at the subcellular scale by combining a fluorescent silica shell suitable for microscopy and a superparamagnetic multicore for the extraction of cellular content.

BSA–MnO2–SAL multifunctional nanoparticle-mediated M1 macrophages polarization for glioblastoma therapy

Schematic illustration of BMS induced M1 macrophage polarization and the antitumor effect.