TCPP-Isoliensinine Nanoparticles for Mild-Temperature Photothermal Therapy.

PURPOSE: Photothermal therapy (PTT) is promising for the treatment of tumors due to its advantages including minimally invasive, easy implementation and selective localized treatment. However, single PTT suffers from several limitations, such as constrained light penetration and low delivery efficiency, typically leading to heterogeneous heating and incomplete elimination of cancer cells. Therefore, combination of PTT with other therapies, eg, chemotherapy is desirable in order to achieve synergistic effects in cancer treatment. METHODS: Here, we designed a new type of TCPP-Iso combined nanoparticle for synergetic therapy for breast cancer. Specifically, photothermal agent tetra(4-carboxyphenyl) porphine (TCPP) and anti-cancer drug isoliensinine (Iso) were encapsulated in PEG-b-PLGA polymeric nanoparticles through a precipitation process. RESULTS: The obtained NPs displayed well-controlled size and high stability over time. Tuning TCPP-Iso/polymer ratio, or total concentration of drug and polymers led to increased hydrodynamic radius of NPs from 65 to 108 nm without disturbing the narrow size distribution. Besides, the formed NPs showed a consequently cumulative release of TCPP and of Iso. The temperature elevation ability of both TCPP NPs and TCPP-Iso NPs was TCPP-concentration dependent. Solutions of TCPP NPs that contained equivalent amount of TCPP with respect to TCPP-Iso NPs, presented the same trend and exhibited non-obvious difference in temperature elevation under certain laser power. The viability of MDA-MB-231 cells treated with TCPP-Iso NPs could be inhibited effectively at a relatively mild temperature (42-43°C) compared to the other groups, which may minimize heat damage to the surrounding healthy tissues. CONCLUSION: The results indicate that the TCPP-Iso combined NPs showed hardly any toxicity to normal tissue cell line, but displayed an efficient synergistic effect for killing cancer cells under laser irradiation. Our study demonstrates that the successful combination of TCPP and Iso realized a synergistic therapy effect at a relatively mild temperature, and the insights obtained here shall be helpful for designing new combined PTT agents for cancer treatment.

Pickering Emulsions Based on the pH-Responsive Assembly of Food-Grade Chitosan.

Few natural, biocompatible, and inexpensive emulsifiers are available because such emulsifiers must satisfy severe requirements, be produced synthetically rather than naturally, be nontoxic, and require minimal effort to produce. Therefore, the synthesis of food-grade and biocompatible nanoparticles as an alternative to surfactants has recently received attention in the industry. However, many previous efforts involved chemical modification of materials or the introduction of secondary cocomponents for emulsion formation. To achieve the goal of simple preparation, we consider here chitosan nanoparticles to prepare Pickering emulsions of food-grade oil through the control of pH, without further chemical modification or extra additives. A mild process can prepare nanoparticles from chitosan by simply increasing the pH from 3.0 to 6.0. The results showed that the average radius of chitosan at pH 6.0 was 170 nm, while large aggregates were formed at pH 6.5. These nanoparticles were utilized to prepare the Pickering emulsion. The average size of emulsion droplets decreased upon increasing the pH from 3.0 to 6.0. Moreover, Pickering emulsions at different oil fractions and nanoparticle concentrations were stable and showed a low creaming index for 45 days. The emulsions were stable against coalescence and flocculation and behaved rheologically as gel-like, shear-thinning fluids (G' > G″). Pickering emulsion prevents the growth of the microorganism (Staphylococcus aureus) at different pH values and chitosan concentrations. These results demonstrate that chitosan nanoparticles could be a cost-effective and biocompatible emulsifier for the food or pharmaceutical industry for encapsulation and bioactive compounds, and Pickering emulsions have promising antibacterial effects for further applications.