Efficient Combination Chemo-Sonodynamic Cancer Therapy Using Mitochondria-Targeting Sonosensitizer-Loaded Polysorbate-Based Micelles.

Sonodynamic therapy (SDT), utilizing ultrasound (US) and sonosensitizers, holds immense potential as a noninvasive and targeted treatment for a variety of deep-seated tumors. However, the clinical translation of SDT is hampered by several key limitations in sonosensitizers, especially their low aqueous stability and poor cellular uptake. In this study, non-ionic polysorbate (Tween 80, T80) was adopted to formulate effective nanocarriers for the safe and efficient delivery of sonosensitizers to cancer cells. Mitochondria-targeting triphenylphosphonium (TPP)-conjugated chlorin e6 (Ce6) sonosensitizer was loaded into T80-based micelles for efficient SDT. Pro-oxidant piperlongumine (PL) was co-encapsulated with TPP-conjugated Ce6 (T-Ce6) in T80 micelles to enable combination chemo-SDT. T80 micelles substantially enhanced the cellular internalization of T-Ce6. As a result, T80 micelles loaded with T-Ce6 and PL [T80(T-Ce6/PL)] significantly elevated intracellular reactive oxygen species (ROS) generation in MCF-7 human breast cancer cells upon US exposure. Moreover, T-Ce6 exhibited selective accumulation within the mitochondria, leading to efficient cell death under US irradiation. Importantly, T80(T-Ce6/PL) micelles caused cancer-specific cell death by selectively triggering apoptosis in cancer cells through PL. This study demonstrated the feasibility of using T80(T-Ce6/PL) micelles for efficient and cancer-specific combination chemo-SDT.

Ring Opening Metathesis Polymerization of Bicyclic α,ß-Unsaturated Anhydrides for Ready-to-be-grafted Polymers Having Tailored pH-Responsive Degradability.

Polymers having α,ß-unsaturated anhydrides as repeating units were synthesized by ring opening metathesis polymerization (ROMP). The anhydride moieties were ready-to-be-grafted with amines to form acid-labile cis-α,ß-unsaturated acid amide linkages. The pH-responsive reversible de-grafting can be controlled by changing the intramolecular accessibility between acid and amide groups. The alendronate-grafted ROMP polymers showed distinct pH-dependent cytotoxicity according to the anhydride structures.

Development of poly(D,L-lactic-co-glycolic acid) films coated with biomembrane-mimicking polymers for anti-adhesion activity.

A physical barrier is one of the most effective strategies to alleviate excessive postoperative adhesion (POA) between tissues at an injury site. To overcome the limitations of current polymeric film-type physical barriers, we suggest a film of poly(lactic-co-glycolic acid) (PLGA) that is non-covalently coated with poly(2-methacryloyloxyethyl phosphorylcholine (MPC)-co-n-butyl methacrylate (BMA)) (PMB). While maintaining the degradability and mechanical properties of PLGA, the PMB coating introduces strong anti-adhesive properties to the film by forming a zwitterionic MPC-based surface through the hydrophobic interactions between BMA moieties and PLGA. Compared to SurgiWrap®, the commercially available poly(lactic acid)-based anti-adhesive film against POA, the PMB-coated PLGA film is much more inhibitory against protein adsorption and fibroblast adhesion, processes that are crucial to the POA process. PMB coating also inhibits the expression of fibronectin containing extra domain A (FN-EDA), α-smooth muscle actin (α-SMA), and collagen type IV alpha 2 (COL4A2), which are marker genes and proteins involved in fibroblast activation and excessive fibrosis during POA. Such inhibitory activities are clearly observed in a 3-dimensional culture of fibroblasts within a collagen matrix, which mimics the in vivo environment of an injury site, as well as in a 2-dimensional culture. The kinetics and the stability of the PMB coating suggest potential future clinical use to coat PLGA films to create a film-type anti-adhesion barrier that overcomes the limitations of current products.

Calcium-Binding Polymer-Coated Poly(lactide- co-glycolide) Microparticles for Sustained Release of Quorum Sensing Inhibitors to Prevent Biofilm Formation on Hydroxyapatite Surfaces.

Quorum sensing (QS) inhibitor-based therapy is an attractive strategy to inhibit bacterial biofilm formation without excessive induction of antibiotic resistance. Thus, we designed Ca2+-binding poly(lactide- co-glycolide) (PLGA) microparticles that can maintain a sufficient concentration of QS inhibitors around hydroxyapatite (HA) surfaces in order to prevent biofilm formation on HA-based dental or bone tissues or implants and, therefore, subsequent pathogenesis. Poly(butyl methacrylate- co-methacryloyloxyethyl phosphate) (PBMP) contains both Ca2+-binding phosphomonoester groups and PLGA-interacting butyl groups. The PBMP-coated PLGA (PLGA/PBMP) microparticles exhibited superior adhesion to HA surfaces without altering the sustained release properties of uncoated PLGA microparticles. PLGA/PBMP microparticle-encapsulating furanone C-30, a representative QS inhibitor, effectively inhibited the growth of Streptococcus mutans and its ability to form biofilms on HA surface for prolonged periods of up to 100 h, which was much longer than either furanone C-30 in its free form or when encapsulated in noncoated PLGA microparticles.

Colloidal stability of iron oxide nanoparticles with multivalent polymer surfactants.

This paper introduces a new approach for preparing magnetic colloidal suspensions with electrostatic repulsion between particles and polyelectrolyte surfactants. The surface charge of the iron oxide particles was positive in acidic aqueous conditions; however the surface charge of the colloid was negative in basic aqueous conditions due to the amphoteric property of Fe2O3. The long-term colloidal stability and particle distribution of the multivalent charged polymers, Poly(4-vinylbenzenesulfonate sodium salt) (PSS), Poly(acrylic acid) (PAA), and Poly(allylamine hydrochloride) (PAH) were compared with the monovalent surfactant sodium dodecyl sulfate (SDS). Both mono- and multivalent surfactant molecules showed good colloidal stability for extended periods of time. However, the particle distribution was dependent on the hydrophobicity of the surfactants' functional groups. Polyelectrolytes with a negatively charged functional group showed good long-term stability of particles and a narrow particle distribution regardless of the acid dissociation constant (pKa) of the polymer.