Transforming a Toxic Non-Ionizable Drug into an Efficacious Liposome via Ionizable Prodrug and Remote Loading Strategies against Malignant Breast Tumors.

Liposomes (lipos), one of the most successful nanotherapeutics in the clinic, have made a rapid advance over the past few years. However, still, several challenges exist for lipos for clinical practice, such as low drug loading and premature drug leakage during in vivo circulation. Paclitaxel (PTX), a commonly used first-line drug for cancer chemotherapy, was chosen as the model drug. Due to its non-ionizable and water-insoluble characteristics, the drug-loading efficiency of the marketable PTX lipos, Lipusu, is only 6.76%. Herein, we designed an ionizable PTX prodrug (PTXP) by modifying phenylboronic acid on the C2' hydroxyl group of PTX for the remote loading of liposomal formulations through the pH gradient method. Compared with Lipusu, PTXP lipos displayed a 34% higher loading efficiency and an encapsulation efficiency of approximately 95%. A series of in vitro/vivo experiments indicated that PTXP lipos possess colloidal stability, prolonged blood circulation, high tumor site accumulation, potent anti-tumor effects, and safety. A combination of ionizable prodrugs and remote loading has proved to be an effective and simple strategy to achieve high liposomal encapsulation efficiency of poorly soluble non-ionizable drugs for clinical application.

Black phosphorus nanosheets-based platform for targeted chemo-photothermal synergistic cancer therapy.

As a new member of two-dimensional (2D) nanomaterials, black phosphorus (BP) has been considered as efficient photothermal therapy (PTT) agents owing to its excellent photothermal efficiency and biodegradability. Herein, a multifunctional nanoplatform based on black phosphorus nanosheets (BP NSs) was developed for chemo-photothermal synergistic cancer therapy. The BP NSs were successfully prepared by a liquid exfoliation technique. Doxorubicin (DOX), as a model drug, was loaded into the cavity of poly (amidoamine) (PAMAM) dendrimer using thin film hydration method. Then, PAMAM@DOX was coated on the surface of BP NSs using an electrostatic adsorption method that combined bath sonication with magnetic stirring. Hyaluronic acid (HA) was also modified onto the BP NS-PAMAM@DOX through electrostatic adsorption. PAMAM and HA layer could effectively isolate BP NSs from water and air to improve physiological stability. BP NSs and BP NS-PAMAM@DOX-HA were characterized by particle size, zeta potential, morphology, UV-vis-NIR absorption spectra, stability, photothermal performance and photothermal stability. This nanosystem exhibited a good pH and near infrared (NIR) dual-responsive drug release property. In addition, the obtained BP NS-PAMAM@D OX-HA nanocomposites possessed excellent PTT efficiency both in vitro and in vivo. The in vitro cell experiments suggested that the targeted BP NS-PAMAM@DOX-HA presented greater cytotoxicity and higher cellular uptake efficiency. Tumor xenograft model was established in BALB/C mice. The therapeutic effect of BP NS-PAMAM@DOX-HA was further augmented under 808 nm laser irradiation, displaying superior antitumor effect in comparison with chemotherapy or PTT alone. Such a biodegradable BP NS-based platform provide new insights for the rational design of PTT-based combinational cancer therapy.