Synthesis and degradation mechanism of renally excretable gold core-shell nanoparticles for combined photothermal and photodynamic therapy.

Photothermal therapy (PTT) has emerged as a very potent therapeutic approach in the treatment of tumors. Gold nanoparticles have gained considerable scientific interest as a photosensitizer due to their absorbance in the near-infrared regions. However, their biodegradation and excretion from the body is a challenge. Various biodegradable systems consisting of liposomes and polymers have been synthesized, but their precise manufacturing and decomposition mechanisms have not yet been explored. Using zein nanoparticles as a template, we have fabricated a glutathione-functionalized gold core shell type of formulation. The scalability of the one-step seedless gold coating process is also reported. The synthesis procedure of these tunable nanoparticles is understood with TEM. The thermal degradation of the material under the physiological conditions is thoroughly examined using UV and TEM. In vitro PTT effectiveness on breast cancer cells is assessed after an extensive in vitro toxicity research. The mechanism of cell death is studied using ROS and cell cycle analysis. The material exhibited good efficacy as a PTT agent in mice and showed non-toxicity up to 14 days. The renal clearance study of the material in mice shows its disintegration into renal clearable minute gold seeds. All the findings suggest biodegradable glutathione-functionalized gold core-shell nanoparticles as potential photothermal cancer treatment agents.

pH-responsive delivery of anti-metastatic niclosamide using mussel inspired polydopamine nanoparticles.

Niclosamide (Nic), an FDA approved antihelminthic drug, is being repurposed as a potent anti-cancer and anti-inflammatory agent. Niclosamide exhibits anti-cancer activity in multiple cancer types, including breast, colon, and prostate cancers. Niclosamide, a BCS II drug, is practically insoluble in water and sparingly soluble in organic solvents (ethanol, dimethyl sulfoxide), leading to limited therapeutic applications, and necessitates the need for a drug carrier. Herein, we report the preparation of polydopamine nanoparticles loaded with niclosamide (Nic-PDA NPs). The designed formulation had a very high loading efficiency (~30%) and entrapment efficiency close to 90%. The average hydrodynamic diameter of Nic-PDA NPs was 146.3 nm, with a narrow size distribution (PDI = 0.039). The formulation exhibited a pH-dependent drug release profile, with ~35% drug released at pH 7.4 after 120 h, compared to > 50% at pH 5.5 in simulated physiological conditions. The NPs exhibited time-dependent cellular uptake and were primarily localized in the cytoplasm. The formulation exhibited comparable cytotoxicity in MDA-MB-231 cells (IC50 = 2.73 µM, 36 h), and inhibited the migration of cancer cells significantly compared to the free drug and unloaded PDA NPs. Furthermore, the unloaded NPs exhibited excellent in vivo compatibility. The study establishes a rigorously optimized protocol for the synthesis of Nic loaded PDA NPs. The biocompatibility, anti-migratory efficacy, and the in vivo non-toxic nature of PDA has been well demonstrated.