Flexible Hollow Human Serum Albumin-Catalase Nanocapsules with High Accumulation and Uptake Ability for Enhanced Photodynamic Therapy.

Introduction: Photodynamic therapy (PDT) has attracted increasing attention for tumor treatment because of its minimal invasiveness and specific spatiotemporal selectivity. However, insufficient tumor accumulation and low cellular uptake of photosensitizers limit its therapeutic efficacy. Methods: In this study, flexible hollow human serum albumin/catalase nanocapsules (HSA/CATs) were created using a core-assisted protein-coating method and combined with the photosensitizer chlorin e6 (HSA/CAT@Ce6) for PDT. Results and Discussion: Transmission electron microscopy (TEM) images demonstrate that HSA/CAT nanocapsules are flexible, with a uniform diameter (310 nm) and a well-defined hollow structure. Thanks to their flexibility, HSA/CAT@Ce6 nanocapsules show a higher cellular uptake than rigid nanoparticles. The nanocapsules effectively generate reactive oxygen species (ROS) in 4T1 cells because of their high cellular uptake and catalytic capacity, remarkably enhancing their in vitro PDT efficacy. In addition, the in vivo tumor accumulation of HSA/CAT@Ce6 nanocapsules is significantly larger than that of rigid nanoparticles and Ce6, meaning they are highly effective in tumor cell ablation. This demonstrates that our flexible nanoplatform holds great promise for enhancing PDT of tumor.

Disrupting stromal barriers to enhance photothermal-chemo therapy using a halofuginone-loaded Janus mesoporous nanoplatform.

Dense tumor stroma is the physiological barrier in drug delivery that prevents anticancer drugs from entering the tumor, thereby seriously limiting the drugs' therapeutic effect. In this study, a Janus nanoplatform consisting of periodic mesoporous organosilica-coated platinum nanoplatforms (JPMO-Pt) and anti-stroma drug halofuginone (HF) (denoted as JPMO-Pt-HF), was developed to deplete the tumor stroma and synergistically treat breast cancer in BALB/c mice. The prepared JPMO-Pt had a uniform size of 245 nm, a good dispersion, an excellent in vitro and in vivo biocompatibility, and a high loading capacity for HF (up to 50 µg/mg). The antitumor experiments showed that the survival rate of 4 T1 cells exhibited an obvious downward trend when the cells were incubated with the JPMO-Pt-HF and irradiated with 808 nm laser. Moreover, the cell survival rate was only about 10% at 48 h when the HF concentration was 2.0 µg/mL. Notably, JPMO-Pt-HF under irradiation had an excellent synergistic therapeutic effect on tumor cells. In vivo antitumor experiment further showed that the JPMO-Pt-HF, in combination with laser irradiation, could minimize tumor growth, showing significantly better effects than those observed for the case of monotherapy involving photothermal therapy (PTT) (152 vs. 670 mm3, p < 0.0001) and HF (152 vs. 419 mm3, p = 0.0208). In addition, immunohistochemistry of tumor tissues indicated that JPMO-Pt-HF obviously reduced the relative collagen and α-smooth muscle actin (α-SMA) area fraction. Taken together, this research designs a new platform that not only possesses the ability to degrade the tumor matrix but also combines PTT and chemotherapeutic effects, and holds promise for effective tumor treatment.

General and facile syntheses of hybridized deformable hollow mesoporous organosilica nanocapsules for drug delivery.

Deformable materials have garnered widespread attention in biomedical applications. Herein, a controllable, general, and simple alkaline etching strategy was used to synthesize deformable hollow mesoporous organosilica nanocapsules (DMONs), in which multiple organic moieties were homogeneously incorporated into the framework. DMONs with double-, triple-, and even quadruple-hybridized frameworks were prepared by the selective introduction of organosilica precursors in accordance with the chemical homology principle through a surfactant-directed sol-gel procedure and a subsequent etching process in alkaline solution. The triple-hybridized DMONs possessed uniform and controllable diameters (100-330 nm), and large hollow cavities (50-270 nm). Liquid cell electron microscopy images demonstrated that the DMONs were deformable in solution. Elemental mapping images suggested that the organic components were homogeneous distribution within the entire DMONs framework. Statistical analysis of cell proliferation assays showed that breast cancer MCF-7 viability exceeded 85% when the cells are incubated with the triple-hybridized DMONs (800 µg mL-1) for 24 h. Histological assessments of main organs indicated no tissue injury or necrosis after intravenous injection of the DMONs 7 days (5 mg kg-1 body weight). Quantitative analysis indicated that the cellular uptake of the DMONs was 6-fold higher than that of their hard counterparts when the number of nanoparticles added was 1.25 × 104, and similar results were found for 4 T1 cells. Furthermore, doxorubicin (DOX) loaded triple-hybridized DMONs with a loading efficiency of 16.9 wt%, produced a strong killing effect on tumor cells. Overall, DMONs with various incorporated organic functional groups could serve as novel nanoplatforms for drug delivery in biomedical applications.