Polymer theranostics with multiple stimuli-based activation of photodynamic therapy and tumor imaging.

Background: Efficient theranostic strategies concurrently bring and use both the therapeutic and diagnostic features, serving as a cutting-edge tool to combat advanced cancers. Goals of the Investigation: Here, we develop stimuli-sensitive theranostics consisting of tailored copolymers forming micellar conjugates carrying pyropheophorbide-a (PyF) attached by pH-sensitive hydrazone bonds, thus enabling the tumor microenvironment-sensitive activation of the photodynamic therapy (PDT) effect, fluorescence or phosphorescence. Results: The nanomedicines show superior anti-tumor PDT efficacy and huge tumor-imaging potential, while reducing their accumulation, and potentially side effects, in the liver and spleen. The developed theranostics exhibit clear selective tumor accumulation at high levels in the mouse sarcoma S180 tumor model with almost no PyF found in the healthy tissues after 48 h. Once in the tumor, illumination at λexc = 420 nm reaches the therapeutic effect due to the 1O2 generation. Indeed, an almost complete inhibition of tumor growth is observed up to 18 days after the treatment. Conclusion: The clear benefit of the specific PyF release and activation in the acidic tumor environment for the targeted delivery and tissue distribution dynamics was proved. Conjugates carrying pyropheophorbide-a (PyF) attached by pH-sensitive hydrazone bonds showed their excellent antitumor PDT effect and its applicability as advanced theranostics at very low dose of PyF.

Octahedral Molybdenum Cluster-Based Nanomaterials for Potential Photodynamic Therapy.

Photo/radiosensitizers, such as octahedral molybdenum clusters (Mo6), have been intensively studied for photodynamic applications to treat various diseases. However, their delivery to the desired target can be hampered by its limited solubility, low stability in physiological conditions, and inappropriate biodistribution, thus limiting the therapeutic effect and increasing the side effects of the therapy. To overcome such obstacles and to prepare photofunctional nanomaterials, we employed biocompatible and water-soluble copolymers based on N-(2-hydroxypropyl)methacrylamide (pHPMA) as carriers of Mo6 clusters. Several strategies based on electrostatic, hydrophobic, or covalent interactions were employed for the formation of polymer-cluster constructs. Importantly, the luminescent properties of the Mo6 clusters were preserved upon association with the polymers: all polymer-cluster constructs exhibited an effective quenching of their excited states, suggesting a production of singlet oxygen (O2(1Δg)) species which is a major factor for a successful photodynamic treatment. Even though the colloidal stability of all polymer-cluster constructs was satisfactory in deionized water, the complexes prepared by electrostatic and hydrophobic interactions underwent severe aggregation in phosphate buffer saline (PBS) accompanied by the disruption of the cohesive forces between the cluster and polymer molecules. On the contrary, the conjugates prepared by covalent interactions notably displayed colloidal stability in PBS in addition to high luminescence quantum yields, suggesting that pHPMA is a suitable nanocarrier for molybdenum cluster-based photosensitizers intended for photodynamic applications.

Polymer-Based Drug-Free Therapeutics for Anticancer, Anti-Inflammatory, and Antibacterial Treatment.

This paper summarizes the area of biomedicinal polymers, which serve as nanomedicines even though they do not contain any anticancer or antiinflammatory drugs. These polymer nanomedicines with unique design are in the literature highlighted as a novel class of therapeutics called "drug-free macromolecular therapeutics." Their therapeutic efficacy is based on the tailored multiple presentations of biologically active vectors, i.e., peptides, oligopeptides, or oligosaccharides. Thus, they enable, for example, to directly induce the apoptosis of malignant cells by the crosslinking of surface slowly internalizing receptors, or to deplete the efficacy of tumor-associated proteins. The precise biorecognition of natural binding motifs by multiple vectors on the polymer construct remains the crucial part in the designing of these drug-free nanomedicines. Here, the rationales, designs, synthetic approaches, and therapeutic potential of drug-free macromolecular therapeutics consisting of various active vectors are described in detail. Recent developments and achievements for namely B-cell lymphoma treatment, Gal-3-positive tumors, inflammative liver injury, and bacterial treatment are reviewed and highlighted. Finally, a possible future prospect within this highly exciting new field of nanomedicine research is presented.

Correction to: The use of clays for chlorhexidine controlled release as a new perspective for longer durability of dentin adhesion.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

High-Affinity N-(2-Hydroxypropyl)methacrylamide Copolymers with Tailored N-Acetyllactosamine Presentation Discriminate between Galectins.

N-Acetyllactosamine (LacNAc; Galß4GlcNAc) is a typical disaccharide ligand of galectins. The most abundant members of these human lectins, galectin-1 (Gal-1) and galectin-3 (Gal-3), participate in a number of pathologies including cancerogenesis and metastatic formation. In this study, we synthesized a series of fifteen N-(2-hydroxypropyl)methacrylamide (HPMA)-based glycopolymers with varying LacNAc amounts and presentations and evaluated the impact of their architecture on the binding affinity to Gal-1 and Gal-3. The controlled radical reversible addition-fragmentation chain transfer copolymerization technique afforded linear polymer precursors with comparable molecular weight (Mn ≈ 22,000 g mol-1) and narrow dispersity (D̵ ≈ 1.1). The precursors were conjugated with the functionalized LacNAc disaccharide (4-22 mol % content in glycopolymer) prepared by enzymatic synthesis under catalysis by ß-galactosidase from Bacillus circulans. The structure-affinity relationship study based on the enzyme-linked immunosorbent assay revealed that the type of LacNAc presentation, individual or clustered on bi- or trivalent linkers, brings a clear discrimination (almost 300-fold) between Gal-1 and Gal-3, reaching avidity to Gal-1 in the nanomolar range. Whereas Gal-1 strongly preferred a dense presentation of individually distributed LacNAc epitopes, Gal-3 preferred a clustered LacNAc presentation. Such a strong galectin preference based just on the structure of a multivalent glycopolymer type is exceptional. The prepared nontoxic, nonimmunogenic, and biocompatible glycopolymers are prospective for therapeutic applications requiring selectivity for one particular galectin.

Preparation of Poly(D,L-lactic-co-glycolic acid) Nanoparticles Through Solvent Displacement and Structural Evaluation Using Time-Domain Nuclear Magnetic Resonance.

The present study obtained coated poly(lactic-co-glycolic acid) nanoparticles using the solvent displacement method aiming to evaluate the effect of the polymer concentration in the pharmaceutical formulations' and polymer properties. Nanosuspensions were evaluated by fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), zeta potential (ZP), thermogravimetric analysis (TGA), X-ray diffraction (XRD) and time-domain nuclear magnetic resonance (TD-NMR). Uniform nanoparticles could be obtained using this method and higher polymer concentrations led to an increase in particle size and negatively charged surfaces were observed. However typical PLGA halo was observed in XRD, diffractograms revealed the Pluronic chains behavior when PLGA concentration changed. Additionally, samples' spin-lattice relaxation times, dipolar interaction and correlation times were evaluated using time-domain nuclear magnetic resonance (TD-NMR), which revealed the interference of PLGA chain packing when Pluronic was incorporated as well as Pluronic chains organization and its behavior around the particle.