Application of a novel multicomponent nanoemulsion to tumor therapy Based on the theory of "unification of drugs and excipients".

Toad skin has many pharmacological activities and bufadienolides are regarded as its main anti-tumor components. The poor water solubility, high toxicity, rapid elimination and less selectivity in vivo of bufadienolides limit the application of toad skin. Based on the "unification of drugs and excipients" theory, the toad skin extracts (TSE) and Brucea javanica oil (BJO) nanoemulsions (NEs) were designed to solve the aforementioned problems. BJO as the main oil phase was not only used to prepare the NEs, but played a synergistic therapeutic role combined with TSE. TSE-BJO NEs showed 155 nm particle size, entrapment efficiency of >95% and good stability. TSE-BJO NEs demonstrated superior anti-tumor activity compared with the TSE or BJO NEs alone. The mechanism of TSE-BJO NEs to enhance the antineoplastic efficacy involved several pathways, such as inhibiting cell proliferation, inducing tumor cell apoptosis >40% and arresting cell cycle at G2/M. TSE-BJO NEs could co-deliver drugs into the target cells efficiently and exhibit satisfying synergism. Besides, TSE-BJO NEs facilitated the long circulation of bufadienolides contributing to the high accumulation of drugs at tumor sites and the improvement of anti-tumor efficacy. The study achieves the combinative administration of the toxic TSE and BJO with high efficacy and safety.

Construction and evaluation of curcumin upconversion nanocarriers decorated with MnO2 for tumor photodynamic therapy.

The limited tissue penetration depth and tumor hypoxic microenvironment have become the two pivotal obstacles that alleviate the antineoplastic efficacy in tumor photodynamic therapy (PDT). In the research, MnO2-decorated upconversion nanoparticles (UCSMn) have been designed to generate certain oxygen within the solid tumor, and also increase the light penetrating depth due to the optical conversion ability derived from upconversion nanoparticles. Furthermore, upconversion nanoparticles as the inner core are coated by mesoporous silica for the loading of curcumin as photosensitizer and chemotherapeutics, and then a MnO2 shell is proceeding to grow via redox method. When reaching the tumor tissue, the MnO2 nanoshells of UCSMn could be rapidly degraded into manganese ions (Mn2+) owing to the reaction with H2O2 in acidic tumor microenvironment, meanwhile producing oxygen and facilitating curcumin release. Once the tumor is illuminated by 980 nm light, the upconversion nanoparticles can transform the infrared light to visible light of 450 nm and 475.5 nm, which can be efficiently absorbed by curcumin, and then produce singlet oxygen to induce tumor cell apoptosis. Curcumin played a dual role which can not only be acted as a photosensitizer, but also a chemotherapeutic agent to further reinforce the antitumor activity. In short, the intelligent nanostructure has the potential to overcome the above-mentioned shortcomings existed in PDT and eventually do work well in the hypoxia tumors. MnO2-decorated upconversion nanoparticle to solve the tissue penetration and tumor hypoxic microenvironment for tumor photodynamic therapy.