Bone targeted nano-drug and nano-delivery.

There are currently no targeted delivery systems to satisfactorily treat bone-related disorders. Many clinical drugs consisting of small organic molecules have a short circulation half-life and do not effectively reach the diseased tissue site. This coupled with repeatedly high dose usage that leads to severe side effects.

RGD Density on Tadpole Nanostructures Regulates Cancer Stem Cell Proliferation and Stemness.

Cancer stem cells (CSCs) make up a small population of cancer cells, primarily responsible for tumor initiation, metastasis, and drug resistance. They overexpress Arg-Gly-Asp (RGD) binding integrin receptors that play crucial roles in cell proliferation and stemness through interaction with the extracellular matrix. Here, we showed that monodisperse polymeric tadpole nanoparticles covalently coupled with different RGD densities regulated colon CSC proliferation and stemness in a RGD density-dependent manner.

A Sequence-Defined ABC Dendritic Macromolecule with Amino Acid Peripheral Functionality via Iterative Chemoselective Reactions.

Chemoselective reactions allow near-precision control over the polymer composition and topology to create sequence-controlled polymers with similar secondary and tertiary structures to those found in proteins. Dendrimers are recognized as well-defined macromolecules with the potential to mimic protein surface functionality due to the large number of functional groups available at its periphery with the internal structure acting as the support scaffold. Transitioning from using small-molecule dendrimers to dendritic macromolecules will not only allow retention of the high peripheral functionality but also provide an internal scaffold with a desired polymer composition within each generational layer.

Multiepitope Subunit Peptide-Based Nanovaccine against Porcine Circovirus Type 2 (PCV2) Elicited High Antibody Titers in Vaccinated Mice.

Porcine circovirus 2 (PCV2) infection is one of the most serious threats to the swine industry. While the disease can be prevented, to some extent, by commercial PCV2a vaccines, the evolving nature of PCV2 necessitates the development of a novel vaccine that can compete with the mutations of the virus. Thus, we have developed novel multiepitope vaccines based on the PCV2b variant.

Liposomal Formulations of a Polyleucine-Antigen Conjugate as Therapeutic Vaccines against Cervical Cancer.

Human papilloma virus (HPV) is responsible for all cases of cervical cancer. While prophylactic vaccines are available, the development of peptide-based vaccines as a therapeutic strategy is still under investigation. In comparison with the traditional and currently used treatment strategies of chemotherapy and surgery, vaccination against HPV is a promising therapeutic option with fewer side effects.

RGD-Coated Polymer Nanoworms for Enriching Cancer Stem Cells.

Cancer stem cells (CSCs) are primarily responsible for tumour drug resistance and metastasis; thus, targeting CSCs can be a promising approach to stop cancer recurrence. However, CSCs are small in numbers and readily differentiate into matured cancer cells, making the study of their biological features, including therapeutic targets, difficult. The use of three-dimensional (3D) culture systems to enrich CSCs has some limitations, including low sphere forming efficiency, enzymatic digestion that may damage surface proteins, and more importantly no means to sustain the stem properties.

Surface Inactivation of Highly Mutated SARS-CoV-2 Variants of Concern: Alpha, Delta, and Omicron.

Continued SARS-CoV-2 transmission among the human population has meant the evolution of the virus to produce variants of increased infectiousness and virulence, coined variants of concern (VOCs). The last wave of pandemic infections was driven predominantly by the delta VOC, but because of continued transmission and adaptive mutations, the more highly transmissible omicron variant emerged and is now dominant. However, due to waning immunity and emergence of new variants, vaccines alone cannot control the pandemic.

Temperature-Directed Formation of Anisotropic Kettlebell and Tadpole Nanostructures in the Absence of a Swelling-Induced Solvent.

Anisotropic Janus ("snowman") nanoparticles with a single protrusion are currently made via the solvent swelling-induced method. Here, we demonstrate without the aid of toxic solvents a generally applicable method for the formation of anisotropic polymer nanoparticles directly in water by controlling polymer mobility through tuning its glass transition temperature (T ). Spherical structures, formed immediately after the emulsion polymerization, transformed into uniform tadpoles (with head diameter ≈60 nm and tail length ≈130 nm) through the protrusion of a single cylindrical tail when cooled to a temperature above the T of the polymer.

Calcium-bisphosphonate Nanoparticle Platform as a Prolonged Nanodrug and Bone-Targeted Delivery System for Bone Diseases and Cancers.

Bone and bone-related diseases are the major cause of mobility hindrance and mortality in humans and there is no effective and safe treatment for most of them, especially, for bone and bone metastatic cancers. Bisphosphonates (BPs) are a group of small-molecule drugs for treating osteoporosis and bone cancers but have a very short half-life in circulation, requiring high doses and long-term repeat use that can cause severe side effects. Previous attempts of using nanoparticles to deliver BPs have issues of drug loading capacity and endosome escape/drug release.

Nonionic Polymer with Flat Upper Critical Solution Temperature Behavior in Water.

We rationally designed a monomer that when polymerized formed a well-defined nonionic polymer [poly(2-(methacryloyloxy) ethylureido glycinamide), PMEGA] by reversible addition fragmentation chain transfer with a flat and tunable upper critical solution temperature (UCST) in water. The monomer was made in one pot from commercially available compounds and with ease of purification. Strong hydrogen-bonding side groups on the polymer produced sharp coil-to-globule transitions upon cooling below its UCST.

Water-Borne Nanocoating for Rapid Inactivation of SARS-CoV-2 and Other Viruses.

The rise in coronavirus variants has resulted in surges of the disease across the globe. The mutations in the spike protein on the surface of the virion membrane not only allow for greater transmission but also raise concerns about vaccine effectiveness. Preventing the spread of SARS-CoV-2, its variants, and other viruses from person to person via airborne or surface transmission requires effective inactivation of the virus.

Mechanisms of cancer stem cell senescence: Current understanding and future perspectives.

Cancer stem cells (CSCs) are a small population of heterogeneous tumor cells with the capacity of self-renewal and aberrant differentiation for immortality and divergent lineages of cancer cells. In contrast to bulky tumor cells, CSCs remain less differentiated and resistant to therapy even when targeted with tissue-specific antigenic markers. This makes CSCs responsible for not only tumor initiation, development, but also tumor recurrence.

Polymer Colloids: Synthesis Fundamentals to Applications.

This special issue of Biomacromolecules highlights research from The International Polymer Colloid Group (IPCG), which was founded in 1972 as a forum for the exchange of ideas and emerging research activities for scientists and engineers from both academia and industry who study or use polymer colloids. The increasing relevance of polymeric structures with colloidal dimensions to biomacromolecules research provided the impetus for organizing this special issue. The IPCG is composed of over 120 researchers from over 20 countries who are elected to membership.

Monodisperse Macromolecules by Self-Interrupted Living Polymerization.

Biological macromolecules such as proteins and nucleic acids are monodisperse just as low-molar-mass organic compounds are. However, synthetic macromolecules contain mixtures of different chain lengths, the most uniform being generated by living polymerizations, which exhibit a maximum of 1-3% of chains with the desired length. Monodisperse natural and synthetic oligomers can be obtained in low quantities by tedious, multistep iterative methods.

Therapeutic Delivery of Polymeric Tadpole Nanostructures with High Selectivity to Triple Negative Breast Cancer Cells.

Targeted delivery of therapeutic drugs using nanoparticles to the highly aggressive triple negative breast cancer cells has the potential to reduce side effects and drug resistance. Cell entry into triple negative cells can be enhanced by incorporating cell binding receptor molecules on the surface of the nanoparticles to enhance receptor-mediated entry pathways, including clatherin or caveolae endocytosis. However, for highly aggressive cancer cells, these pathways may not be effective, with the more rapid and high volume uptake from macropinocytosis or phagocytosis being significantly more advantageous.

Temperature-Induced Formation of Uniform Polymer Nanocubes Directly in Water.

Conventional self-assembly methods of block copolymers in cosolvents (i.e., usually water and organic solvents) has yet to produce a pure and monodisperse population of nanocubes.

Cancer stemness contributes to cluster formation of colon cancer cells and high metastatic potentials.

The ability of cancer cells to form clusters is a characteristic feature in the development of metastatic tumours with drug resistance. Several studies demonstrated that clusters of circulating tumour cells (CTCs) have a greater metastatic potential to establish new tumours at secondary sites than single CTCs. However, the mechanism of cluster formation is not well understood.

Replacing Cu(II)Br with Me-TREN in Biphasic Cu(0)/TREN Catalyzed SET-LRP Reveals the Mixed-Ligand Effect.

The mixed-ligand system consisting of tris(2-aminoethyl)amine (TREN) and tris(2-dimethylaminoethyl)amine (Me-TREN) during the Cu(0) wire-catalyzed single electron transfer-living radical polymerization (SET-LRP) of methyl acrylate (MA) in "programmed" biphasic mixtures of the dipolar aprotic solvents NMP, DMF, and DMAc with HO is reported. Kinetic and chain end analysis studies by NMR and MALDI-TOF before and after thio-bromo "click" reaction demonstrated that Me-TREN complements and makes the less expensive TREN a very efficient ligand in the absence of externally added Cu(II)Br. Statistical analysis of the kinetic data together with control experiments demonstrated that this mixed-ligand effect enhanced the apparent rate constant of propagation, monomer conversion, and molecular weight control.

UV-Cross-Linked Polymer Nanostructures with Preserved Asymmetry and Surface Functionality.

Polymer nanostructures can be designed with tailored properties and functions by varying their shape, chemical compositions, and surface functionality. The poor stability of these soft materials in solvent other than water can be overcome by introducing cross-links. However, cross-linking complex morphologies remains a challenge.

Viscoelastic Properties of Unentangled Multicyclic Polystyrenes.

We report on the viscoelastic properties of linear, monocyclic, and multicyclic polystyrenes with the same low molecular weight. All polymers investigated were found to exhibit unentangled dynamics. For monocyclic polymers without inner loops, a cyclic-Rouse model complemented by the contribution of unlinked chains (whose fraction was determined experimentally) captured the observed rheological response.

Conjugated Nitroxide Radical Polymers: Synthesis and Application in Flexible Energy Storage Devices.

The synthesis and electrochemical behavior of nitroxide radical conjugated polymers (NCPs) have long been an intriguing topic in redox polymer-based energy storage. However, common (electro)chemical oxidation polymerization methods have proved difficult in the synthesis of well-defined NCPs, and many of these polymers have been difficult to process into thin films. In addition to these drawbacks and coupled with the complex charge-transfer and storage mechanisms, the use of NCPs as electrodes has been significantly limited.

Uniform Symmetric and Asymmetric Polymer Nanostructures via Directed Chain Organization.

Polymer nanostructures can be designed with specific properties and functions, such as controlled shape, size, chemical composition, and adaptive ability to change shape or size in response to environmental cues. Precise control to organize polymer chains into uniform nonspherical symmetric and asymmetric nanostructures and at scale remains a synthetic challenge. Here, by using the temperature-directed morphology transformation (TDMT) method we show through a systematic organization of polymer chains the synthesis of well-defined asymmetric (i.

Biodistribution of PNIPAM-Coated Nanostructures Synthesized by the TDMT Method.

Targeting the spleen with nanoparticles could increase the efficacy of vaccines and cancer immunotherapy, and have the potential to treat intracellular infections including leishmaniasis, trypanosome, splenic TB, AIDS, malaria, and hematological disorders. Although, nanoparticle capture in both the liver and spleen has been well documented, there are only a few examples of specific capture in the spleen alone. It is proposed that the larger the nanoparticle size (>400 nm) the greater the specificity and capture within the spleen.