Thermoresponsive Alginate-Graft-pNIPAM/Methyl Cellulose 3D-Printed Scaffolds Promote Osteogenesis In Vitro.

In this work, a sodium alginate-based copolymer grafted by thermoresponsive poly(-isopropylacrylamide) (PNIPAM) chains was used as gelator (Alg-g-PNIPAM) in combination with methylcellulose (MC). It was found that the mechanical properties of the resulting gel could be enhanced by the addition of MC and calcium ions (Ca). The proposed network is formed via a dual crosslinking mechanism including ionic interactions among Ca and carboxyl groups and secondary hydrophobic associations of PNIPAM chains.

Harnessing the Interplay of Triple Cross-Linked Hydrogels toward Multiresponsive Alginate-Based Injectable Gels for 3D Printing Bioapplications.

We report on a single chain polymer gelator comprising an alginate backbone double grafted with thermoresponsive P(NIPAM--NtBAM)-NH polymer grafts and 3-aminophenylboronic acid moieties. The resulting polymer forms robust polymer networks resulting from three cooperative cross-linking mechanisms: (i) the hydrophobic association of the T-responsive polymer grafts above 24 °C, (ii) the formation of boronate esters between the boronic acid and the diols of the alginate backbone at physiological pH, and (iii) the ionic interactions of the residual carboxylate moieties with Ca ions. The resulting material showed excellent tunability of the mechanical properties driven by stimuli combinations such as temperature, pH, or the addition of glucose as a network disruptor covering a storage modulus range from ∼260 Pa up to ∼1390 Pa by selective stimuli combinations.

Dually crosslinked injectable alginate-based graft copolymer thermoresponsive hydrogels as 3D printing bioinks for cell spheroid growth and release.

In this work a dual crosslinked network based on sodium alginate graft copolymer, bearing poly(N-isopropylacrylamide-co-N-tert-butylacrylamide) P(NIPAM-co-NtBAM) side chains was developed and examined as a shear thinning soft gelating bioink. The copolymer was found to undergo a two-step gelation mechanism; in the first step a three-dimensional (3D) network is formed through ionic interactions between the negatively ionized carboxylic groups of the alginate backbone and the positive charges of Ca divalent cations, according to the "egg-box" mechanism. The second gelation step occurs upon heating which triggers the hydrophobic association of the thermoresponsive P(NIPAM-co-NtBAM) side chains, increasing the network crosslinking density in a highly cooperative manner.

Photochemical Internalization Using Natural Anticancer Drugs, Antimetabolites, and Nanoformulations: A Systematic Study against Breast and Pancreatic Cancer Cell Lines.

Photochemical internalization (PCI) is a novel, minimally invasive drug delivery technology that facilitates the delivery of therapeutic molecules into the cytosol of cells. In this work, PCI was utilized in an effort to enhance the therapeutic index of the existing anticancer drugs as well as novel nanοformulations against breast and pancreatic cancer cells. Frontline anticancer drugs were tested with bleomycin as a benchmark PCI control; namely, three vinca alkaloids (vincristine, vinorelbine, and vinblastine), two taxanes (docetaxel and paclitaxel), two antimetabolites (gemcitabine and capecitabine), a combination of taxanes with antimetabolites, and two nano-sized formulations (squalene- and polymer-bound gemcitabine derivatives) were tested in a 3D PCI in vitro model.

Recent developments in the use of gold and silver nanoparticles in biomedicine.

Gold and silver nanoparticles (NPs) are widely used in the biomedical research both in the therapeutic and the sensing/diagnostics fronts. Both metals share some common optical properties with surface plasmon resonance being the most widely exploited property in therapeutics and diagnostics. Au NPs exhibit excellent light-to-heat conversion efficiencies and hence have found applications primarily in precision oncology, while Ag NPs have excellent antibacterial properties which can be harnessed in biomaterials' design.

Polymer coated gold nanoshells for combinational photochemotherapy of pancreatic cancer with gemcitabine.

Pancreatic cancer is one of the most lethal malignancies with limited therapeutic options and dismal prognosis. Gemcitabine is the front-line drug against pancreatic cancer however with limited improvement of therapeutic outcomes. In this study we envisaged the integration of GEM with gold nanoshells which constitute an interesting class of nanomaterials with excellent photothermal conversion properties.

Solid lipid nanoparticles self-assembled from spray dried microparticles.

We report the self-assembly of drug-loaded solid lipid nanoparticles (SLNs) from spray dried microparticles comprising poly(vinylpyrrolidone) (PVP) loaded with glyceryl tristearate (GTS) and either indomethacin (IMC) or 5-fluorouracil (5-FU). When the spray dried microparticles are added to water, the PVP matrix dissolves and the GTS and drug self-assemble into SLNs. The SLNs provide a non-toxic delivery platform for both hydrophobic (IMC) and hydrophilic (5-FU) drugs.

Comparison of Thermoresponsive Hydrogels Synthesized by Conventional Free Radical and RAFT Polymerization.

We compared the influence of the polymerization mechanism onto the physical characteristics of thermoresponsive hydrogels. The Poly(-isopropylacrylamide) (PNIPAAm) hydrogels were successfully synthesized using reversible addition-fragmentation chain-transfer (RAFT) and free radical polymerization (FRP). The gels were prepared while using different crosslinker feed and monomer concentration.

Cell membrane engineering with synthetic materials: Applications in cell spheroids, cellular glues and microtissue formation.

Biologically inspired materials with tunable bio- and physicochemical properties provide an essential framework to actively control and support cellular behavior. Cell membrane remodeling approaches benefit from the advances in polymer science and bioconjugation methods, which allow for the installation of un-/natural molecules and particles on the cells' surface. Synthetically remodeled cells have superior properties and are under intense investigation in various therapeutic scenarios as cell delivery systems, bio-sensing platforms, injectable biomaterials and bioinks for 3D bioprinting applications.

Dual Controlled Delivery of Gemcitabine and Cisplatin Using Polymer-Modified Thermosensitive Liposomes for Pancreatic Cancer.

Although combinational anticancer chemotherapies have been proven to improve the life expectancy of patients in the clinic, their full potential is severely limited by the additive toxicities of the drug molecules. Targeted drug delivery systems could alleviate this major limitation by the design of nanocarriers that can cocarry multiple drug molecules in order to augment drug synergism at the site of interest while reducing the systemic side effects. In this study, we report on a thermoresponsive polymer-coated liposome nanocarrier that is capable to cocarry two potent anticancer drugs and release them via a thermally triggered mechanism.

Dual controlled delivery of squalenoyl-gemcitabine and paclitaxel using thermo-responsive polymeric micelles for pancreatic cancer.

In this study we report the synthesis of a themroresponsive block copolymer by reversible addition fragmentation transfer polymerization comprising poly(2-ethylhexyl methacrylate)-b-poly[di(ethylene glycol)methyl ether methacrylate-co-oligo(ethylene glycol)methyl ether methacrylate] as hydrophobic and thermoresponsive blocks respectively. The polymer self-assembles into sub-50 micelles and can carry simultaneously two drug molecules, namely squalene-gemcitabine and paclitaxel. Both drugs can be released from the micellar compartment in a thermally controlled manner owing to the controllable disruption of the micellar corona above the lower critical solution temperature of the polymer.

Development of a Gemcitabine-Polymer Conjugate with Prolonged Cytotoxicity against a Pancreatic Cancer Cell Line.

Gemcitabine (GEM) is a nucleoside analogue of deoxycytidine with limited therapeutic efficacy due to enzymatic hydrolysis by cytidine deaminase (CDA) resulting in compromised half-life in the bloodstream and poor pharmacokinetics. To overcome these limitations, we have developed a methacrylate-based GEM-monomer conjugate, which was polymerized by reversible addition-fragmentation chain transfer (RAFT) polymerization with high monomer conversion (∼90%) and low dispersity (<1.4).

Electrosprayed Janus Particles for Combined Photo-Chemotherapy.

This work is a proof of concept study establishing the potential of electrosprayed Janus particles for combined photodynamic therapy-chemotherapy. Sub-micron-sized particles of polyvinylpyrrolidone containing either an anti-cancer drug (carmofur) or a photosensitiser (rose bengal; RB), and Janus particles containing both in separate compartments were prepared. The functional components were present in the amorphous form in all the particles, and infrared spectroscopy indicated that intermolecular interactions formed between the different species.

Rapid Formation of Cell Aggregates and Spheroids Induced by a "Smart" Boronic Acid Copolymer.

Cell surface engineering has emerged as a powerful approach to forming cell aggregates/spheroids and cell-biomaterial ensembles with significant uses in tissue engineering and cell therapeutics. Herein, we demonstrate that cell membrane remodeling with a thermoresponsive boronic acid copolymer induces the rapid formation of spheroids using either cancer or cardiac cell lines under conventional cell culture conditions at minute concentrations. It is shown that the formation of well-defined spheroids is accelerated by at least 24 h compared to non-polymer-treated controls, and, more importantly, the polymer allows for fine control of the aggregation kinetics owing to its stimulus response to temperature and glucose content.

Macromolecular cell surface engineering for accelerated and reversible cellular aggregation.

We report the synthesis of two simple copolymers that induce rapid cell aggregation within minutes in a fully reversible manner. The polymers can act as self-supporting "cellular glues" or as "drivers" of 3D cell spheroids/aggregates formation at minute concentrations.

Harnessing photochemical internalization with dual degradable nanoparticles for combinatorial photo-chemotherapy.

Light-controlled drug delivery systems constitute an appealing means to direct and confine drug release spatiotemporally at the site of interest with high specificity. However, the utilization of light-activatable systems is hampered by the lack of suitable drug carriers that respond sharply to visible light stimuli at clinically relevant wavelengths. Here, a new class of self-assembling, photo- and pH-degradable polymers of the polyacetal family is reported, which is combined with photochemical internalization to control the intracellular trafficking and release of anticancer compounds.

Light-induced generation of singlet oxygen by naked gold nanoparticles and its implications to cancer cell phototherapy.

Generation of singlet oxygen by direct irradiation of naked gold nanoparticles is observed using either continuous wave or pulsed laser sources. The underlying mechanism involves plasmon- and hot-electron-mediated reaction pathways and (1) O2 seems to significantly amplify the overall death rates during photothermal treatment of cancer cell lines in vitro.

Photodegradable polymers for biotechnological applications.

Photodegradable polymers constitute an emerging class of materials that finds numerous applications in biotechnology, biomedicine, and nanoscience. This article highlights some of the emerging applications of photodegradable polymers in the form of homopolymers, particles and self-assembled constructs in solution, hydrogels for tissue engineering, and photolabile polymers for biopatterning applications. Novel photochemistries have been combined with controlled polymerization methods, which result in well-defined photodegradable materials that exhibit light mediated and often controlled fragmentation processes.

Synthetic polymers for simultaneous bacterial sequestration and quorum sense interference.

Double agents: dual-action polymers are able to sequester rapidly the marine organism Vibrio harveyi from suspension, while at the same time quenching bacterial quorum sense (QS) signals. The potency of the polymers is assessed by cell aggregation experiments and competitive binding assays against a QS signal precursor, and their effect on bacterial behavior is shown by means of bioluminescence.

Controlled polymer synthesis--from biomimicry towards synthetic biology.

The controlled assembly of synthetic polymer structures is now possible with an unprecedented range of functional groups and molecular architectures. In this critical review we consider how the ability to create artificial materials over lengthscales ranging from a few nm to several microns is generating systems that not only begin to mimic those in nature but also may lead to exciting applications in synthetic biology (139 references).

Ion-sensitive "isothermal" responsive polymers prepared in water.

Ion-sensitive responsive polymers are prepared under fully aqueous conditions using controlled radical polymerization. Variations in comonomer content and sequence lead to temperature and salt-dependent solution behavior, with cloud-points ranging by +/-40 degrees C following addition of Hofmeister series salts. A "hybrid" block copolymer, composed of a statistical sequence of monomers tipped with a hydrophilic block, formed stable micelle-like assemblies that exhibited burst release of an encapsulated model drug in response to addition of a kosmotrope, Na2SO4, at room temperature.

Synthetic polymers for capture and detection of microorganisms.

Methods for the detection of pathogens and their deactivation are of paramount importance for public health and security. In this review we highlight some recent examples of sophisticated synthetic polymers and macromolecular constructs that can be used to interact selectively with target pathogens. The biomimetic properties of these materials lend themselves not just to high specificity interactions with target pathogens, but also towards novel capture and deactivation mechanisms.