Novel temperature responsive polymer based sealant for embolization.

A sealant has been developed that improves upon current catheter-based treatments in the following ways: 1) Efficient delivery system, 2) No in situ polymerization, 3) No harmful byproducts, and 4) Cost-effective formulation. During the development process, particular attention was given to materials that were tunable, safe, and effective sealant agents. The thermo-responsive properties of poly(N-isopropylacrylamide) (PNIPAM) provides an ideal foundation to develop an optimized solution. Through a combination of model-based and material testing, a hydrogel was developed that balances conformational factors to achieve a customized transition temperature, radiopacity suitable for visualization, mechanical properties suitable for delivery via 3Fr catheter, sufficient cohesion once applied to resist migration under physiological pressures and an improved safety profile. Two applications, embolization of lymphatic leakage and exclusions of the left atrial appendage (LAA), to eliminate LAA dead space to reduce the risk of thromboembolic events, were considered. The material and benchtop results for this product demonstrate the suitability of this new material not only for these applications but also for other potential healthcare applications.

A sealant has been developed that improves upon current catheter-based treatments in the following ways: 1) Efficient delivery system, 2) No in situ polymerization, 3) No harmful byproducts, and 4) Cost-effective formulation.

Photochemical Synthesis of Sericin-Coated Gold Nanorods and Their Antibacterial Activity under Low-Level Near-Infrared Light.

Gold nanorods (GNRs) are unique nanoparticles with easily functionalized surfaces, multiple synthesis methods, photothermal conversion, and surface plasmon resonance effects. These properties make GNRs suitable for various biological applications. However, a rapid synthesis of GNRs using less toxic chemicals is needed. The photochemical method is a viable option that can synthesize GNRs quickly while using fewer chemicals. A photochemical method is reported for the synthesis of GNRs using Irgacure-2959 as a reducing agent. This method could be used to synthesize GNRs with a rod-like shape within 30 min. Additionally, GNRs were coated with sericin (GNRs-SC) to further reduce their toxicity in human dermal fibroblast adult cells. Low-level near-infrared (NIR) light was applied to enhance the photothermal therapy of both GNRs and GNRs-SC. The results showed that GNRs and GNRs-SC under low-level NIR light have enhanced antibacterial activity against Staphylococcus aureus and Escherichia coli, as well as antibiofilm activity against S. aureus. Furthermore, GNRs-SC showed good biocompatibility with antibacterial and antibiofilm activities. These results indicate that GNRs-SC are good candidates for various biological applications.

Acid-Responsive Polymer Micelles for Targeted Delivery and Bioorthogonal Activation of Prodrug through Ru Catalyst in Tumor Cells.

Bioorthogonal reactions present a promising strategy for minimizing off-target toxicity in cancer chemotherapy, yet a dependable nanoplatform is urgently required. Here, we have fabricated an acid-responsive polymer micelle for the specific delivery and activation of the prodrug within tumor cells through Ru catalyst-mediated bioorthogonal reactions. The decomposition of micelles, triggered by the cleavage of the hydrazone bond in the acidic lysosomal environment, facilitated the concurrent release of Alloc-DOX and the Ru catalyst within the cells. Subsequently, the uncaging process of Alloc-DOX was demonstrated to be induced by the high levels of glutathione within tumor cells. Notably, the limited glutathione inside normal cells prevented the conversion of Alloc-DOX into active DOX, thereby minimizing the toxicity toward normal cells. In tumor-bearing mice, this nanoplatform exhibited enhanced efficacy in tumor suppression while minimizing off-target toxicity. Our study provides an innovative approach for in situ drug activation that combines safety and effectiveness in cancer chemotherapy.

Mussel-Inspired Polymer-Based Coating Technology for Antifouling and Antibacterial Properties.

Zwitterionic coatings provide a promising antifouling strategy against biofouling adhesion. Quaternary ammonium cationic polymers can effectively kill bacteria on the surface, owing to their positive charges. This strategy can avoid the release of toxic biocides, which is highly desirable for constructing coatings for biomedical devices. The present work aims to develop a facile method by covalently grafting zwitterionic and cationic copolymers containing aldehydes to the remaining amine groups of self-polymerized dopamine. Reversible addition-fragmentation chain transfer polymerization was used to copolymerize either zwitterionic 2-methacryloyloxyethyl phosphorylcholine monomer (MPC) or cationic 2-(methacryloyloxy)ethyl trimethylammonium monomer (META) with 4-formyl phenyl methacrylate monomer (FPMA), and the formed copolymers poly(MPC-st-FPMA) and poly(META-st-FPMA) are denoted as MPF and MTF, respectively. MPF and MTF copolymers were then covalently grafted onto the amino groups of polydopamine-coated surfaces. PDA/MPF/MTF-coated surfaces exhibited antibacterial and antifouling properties against S. aureus, E. coli, and bovine serum albumin protein. In addition, they showed excellent viability of normal human lung fibroblast cells MRC-5. We expect the facile surface modification strategy discussed here to be applicable to medical device manufacturing.

Self-Healing Guar Gum-Based Nanocomposite Hydrogel Promotes Infected Wound Healing through Photothermal Antibacterial Therapy.

Preventing bacterial infections is a crucial aspect of wound healing. There is an urgent need for multifunctional biomaterials without antibiotics to promote wound healing. In this study, we fabricated a guar gum (GG)-based nanocomposite hydrogel, termed GBTF, which exhibited photothermal antibacterial therapy for infected wound healing. The GBTF hydrogel formed a cross-linked network through dynamic borate/diol interactions between GG and borax, thereby exhibiting simultaneously self-healing, adaptable, and injectable properties. Additionally, tannic acid (TA)/Fe3+ nanocomplexes (NCs) were incorporated into the hydrogel to confer photothermal antibacterial properties. Under the irradiation of an 808 nm near-infrared laser, the TA/Fe3+ NCs in the hydrogel could rapidly generate heat, leading to the disruption of bacterial cell membranes and subsequent bacterial eradication. Furthermore, the hydrogels exhibited good cytocompatibility and hemocompatibility, making them a precandidate for preclinical and clinical applications. Finally, they could significantly promote bacteria-infected wound healing by reducing bacterial viability, accelerating collagen deposition, and promoting epithelial remodeling. Therefore, the multifunctional GBTF hydrogel, which was composed entirely of natural substances including guar gum, borax, and polyphenol/ferric ion NCs, showed great potential for regenerating infected skin wounds in clinical applications.

Tannic Acid-Based Coatings Containing Zwitterionic Copolymers for Improved Antifouling and Antibacterial Properties.

The prevention of biofilm formation on medical devices has become highly challenging in recent years due to its resistance to bactericidal agents and antibiotics, ultimately resulting in chronic infections to medical devices. Therefore, developing inexpensive, biocompatible, and covalently bonded coatings to combat biofilm formation is in high demand. Herein, we report a coating fabricated from tannic acid (TA) as an adhesive and a reducing agent to graft the zwitterionic polymer covalently in a one-step method. Subsequently, silver nanoparticles (AgNPs) are generated in situ to develop a coating with antifouling and antibacterial properties. To enhance the antifouling property and biocompatibility of the coating, the bioinspired zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) was copolymerized with 2-aminoethyl methacrylamide hydrochloride (AEMA) using conventional free-radical polymerization. AEMA moieties containing amino groups were used to facilitate the conjugation of the copolymer with quinone groups on TA through the Michael addition reaction. Three copolymers with different ratios of monomers were synthesized to understand their impacts on fouling resistance: PMPC100, p(MPC80-st-AEMA20), and p(MPC90-st-AEMA10). To impart antibacterial properties to the surface, AgNPs were formed in situ, utilizing the unreacted quinone groups on TA, which can reduce the silver ions. The successful coating of TA and copolymer onto the surfaces was confirmed by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, and its excellent wettability was verified by the water contact angle (CA). Furthermore, the functionalized coatings showed antibacterial properties against E. coli and S. aureus and remarkably decreased the adhesion of the BSA protein. The surfaces can also prevent the adhesion of bacteria cells, as confirmed by the inhibition zone test. In addition, they showed negligible cytotoxicity to normal human lung fibroblast cells (MRC-5). The as-prepared coatings are potentially valuable for biomedical applications.

Dual-Protection Inorganic-Protein Coating on Mg-Based Biomaterials through Tooth-Enamel-Inspired Biomineralization.

Biocompatible magnesium alloys represent revolutionary implantable materials in dentistry and orthopedics but face challenges due to rapid biocorrosion, necessitating protective coatings to mitigate dysfunction. Directly integrating durable protective coatings onto Mg surfaces is challenging because of intrinsic low coating compactness. Herein, inspired by tooth enamel, a novel highly compact dual-protection inorganic-protein (inorganicPro) coating is in situ constructed on Mg surfaces through bovine serum albumin (BSA) protein-boosted reaction between sodium fluoride (NaF) and Mg substrates. The association of Mg ions and BSA establishes a local hydrophobic domain that lowers the formation enthalpy of NaMgF3 nanoparticles. This process generates finer nanoparticles that function as "bricks," facilitating denser packing, consequently reducing voidage inside coatings by over 50% and reinforcing mechanical durability. Moreover, the incorporation of BSA in and on the coatings plays two synergistic roles: 1) acting as "mortar" to seal residual cracks within coatings, thereby promoting coating compactness and tripling anticorrosion performance, and 2) mitigating fouling-accelerated biocorrosion in complex biosystems via tenfold resistance against biofoulant attachments, including biofluids, proteins, and metabolites. This innovative strategy, leveraging proteins to alter inorganic reactions, benefits the future coating design for Mg-based and other metallic materials with tailored anticorrosion and antifouling performances.

Fabrication of antimicrobial cationic hydrogels driven by physically and chemically crosslinking for wound healing.

The wound therapy based on antibiotic delivery inevitably leads to the emergence of drug resistance. Hydrogel biomaterials with inherent antibacterial activities have emerged as promising candidates for addressing this issue. However, developing an inherently antibacterial hydrogel through simple and facile strategies to promote localized wound infection healing remains a challenge. In this study, we successfully constructed antimicrobial cationic hydrogels with self-healing and injectable properties through physically and chemically dual-crosslinked networks. The networks were formed by the copolymers poly[(di(ethylene glycol) methyl ether methacrylate)-co-(4-formylphenyl methacrylate)-co-(2-(methacryloyloxy)ethyl]trimethylammonium chloride solution)] (PDFM) and poly[(di(ethylene glycol) methyl ether methacrylate)-co-(2-aminoethyl methacrylate hydrochloride)-co-(2-(((6-(6-methyl-4[1H]pyrimidionylureido) hexyl)carbamoyl)oxy)ethyl methacrylate)] (PDAU). The hydrogel systems effectively facilitate the regeneration and healing of infected wounds through the contact bactericidal feature of quaternary ammonium cations. The presence of Schiff base bonds in the injectable hydrogels imparts remarkable pH responsiveness and self-healing properties. In vitro experiments verified their intrinsic antibacterial activities along with their favorable cytocompatibility and hemocompatibility in both in vitro and in vivo. In addition, the hydrogel significantly accelerated the healing of bacterially infected in a full-thickness skin wound. This facilely prepared dual-crosslinked hydrogel, without antibiotics loading, holds significant prospects for treating infected wounds.

Characterization of Cellulose Fiber Derived from Hemp and Polyvinyl Alcohol-Based Composite Hydrogel as a Scaffold Material.

Cellulose nanocrystals (CNCs) were successfully extracted and purified from hemp using an alkaline treatment and bleaching process and subsequently used in conjunction with polyvinyl alcohol to form a composite hydrogel. Cellulose nanocrystals (1-10% (w/v)) were integrated into polyvinyl alcohol, and sodium tetraborate (borax) was employed as a crosslinking agent. Due to the small number of cellulose nanocrystals, no significant peak change was observed in the FT-IR spectra compared to pristine polyvinyl alcohol. The porosity was created upon the removal of the water molecules, and the material was thermally stable up to 200 °C. With the presence of cellulose nanocrystals, the melting temperature was slightly shifted to a higher temperature, while the glass transition temperature remained practically unchanged. The swelling behavior was examined for 180 min in deionized water and PBS solution (pH 7.4) at 37 °C. The degree of swelling of the composite with cellulose nanocrystals was found to be higher than that of pristine PVA hydrogel. The cell viability (%) of the prepared hydrogel with different proportions of cellulose nanocrystals was higher than that of pristine PVA hydrogel. Based on the results, the prepared composite hydrogels from cellulose nanocrystals extracted from hemp and polyvinyl alcohol were revealed to be an excellent candidate for scaffold material for medical usage.

Highly Stretchable, Self-Healing, Injectable and pH Responsive Hydrogel from Multiple Hydrogen Bonding and Boron-Carbohydrate Interactions.

A simple and cost-effective method for the fabrication of a safe, dual-responsive, highly stretchable, self-healing and injectable hydrogel is reported based on a combination of dynamic boronate ester bonds and hydrogen bonding interactions. The mechanical properties of the hydrogel are tunable by adjusting the molar ratios between sugar moieties on the polymer and borax. It was remarkable to note that the 2:1 ratio of sugar and borate ion significantly improves the mechanical strength of the hydrogel. The injectability, self-healing and stretchability properties of the hydrogel were also examined. In addition, the impact of the variation of the pH and the addition of free sugar responsiveness of the hydrogel was studied. High MRC-5 cell viability was noticed by the 3D live/dead assay after 24 h cell culture within the hydrogel scaffold. Hence, the developed hydrogels have desirable features that warrant their applications for drug delivery, scaffolds for cell and tissue engineering.

Glycopolymer-based multifunctional antibacterial hydrogel dressings for accelerating cutaneous wound healing.

Antimicrobial hydrogel dressings have received extensive attention for their wide and promising applications in preventing infections associated with wound healing. However, the development of versatile antibacterial hydrogels inevitably leads to complex structures, which restricts their applications. In this work, a multifunctional antibacterial hydrogel based on a reversible diolborate bond crosslinked network was prepared via the interactions between the zwitterionic glycopolymer poly[(2-methacryloyloxyethyl phosphorylcholine)-co-(N,N-dimethylacrylamide)-co-(2-lactobionamidoethyl methacrylamide)] (PMDL) and borax in conjunction with a simple mixing of Ag NPs within 10 s. The obtained PMDL-12%/borax/Ag NP hydrogel displays a rapid self-healing ability and excellent injectability, as well as good adhesiveness to biological tissues and surfaces of various materials. Moreover, the hydrogels exhibit efficient antibacterial activities against Escherichia coli and Staphylococcus aureus, which could prevent bacterial infections in wound care. The multifunctional hydrogel also shows good cytocompatibility and hemocompatibility. Importantly, in vivo wound healing evaluation of a mouse full-thickness skin defect model confirms that the hydrogel effectively accelerates cutaneous regeneration and wound healing by regulating inflammation and promoting collagen deposition. This multifunctional wound dressing hydrogel prepared using a facile strategy has promising application in biomedical areas.

Green synthesis of nano silver-embedded carboxymethyl starch waste/poly vinyl alcohol hydrogel with photothermal sterilization and pH-responsive behavior.

Bacterial wound infections remain a significant health issue of great concern. Hence, there is a need to develop a novel material with antibacterial properties and smart functions. In this study, the effects of silver nanoparticles content (AgNPs) on properties of photothermal and pH-responsive nanocomposite hydrogels were investigated. The nanocomposite hydrogel samples were prepared using cassava starch waste modified by carboxymethylation (CMS), and mixed with poly vinly alcohol (PVA) and tannic acid (TA). The presence of AgNPs in the hydrogel samples enhanced antibacterial activities and photothermal conversion ability. The use of as-prepared hydrogel using 200 mM silver nitrate (H-AgNPs-200) combined with near infrared (NIR) radiation produced 100 % antibacterial efficiency for Escherichia coli (E.coli) and 98.2 % for Staphylococcus aureus (S.aureus). Furthermore, the H-AgNPs-200 also provided the highest storage modulus at 8.78 kPa. The obtained nanocomposite hydrogel was shown to exhibit pH-responsive release of TA. Under NIR radiation, higher release of TA at different pH was observed. The cytotoxicity study indicated that the nanocomposite hydrogels had good biocompatibility. Hence, the development of nanocomposite hydrogel-based CMS from cassava starch waste/PVA/AgNPs is a promising and sustainable approach where agro-waste product is used as the base material for medical application in wound dressing.

Optimized Carbohydrate-Based Nanogel Formulation to Sensitize Hypoxic Tumors.

Solid tumors are often poorly vascularized, which impairs oxygen supply and drug delivery to the cells. This often leads to genetic and translational adaptations that promote tumor progression, invasion, metastasis, and resistance to conventional chemo-/radiotherapy and immunotherapy. A hypoxia-directed nanosensitizer formulation of a hypoxia-activated prodrug (HAP) was developed by encapsulating iodoazomycin arabinofuranoside (IAZA), a 2-nitroimidazole nucleoside-based HAP, in a functionally modified carbohydrate-based nanogel, facilitating delivery and accrual selectively in the hypoxic head and neck and prostate cancer cells. Although IAZA has been reported as a clinically validated hypoxia diagnostic agent, recent studies have pointed to its promising hypoxia-selective anti-tumor properties, which make IAZA an excellent candidate for further exploration as a multimodal theranostic of hypoxic tumors. The nanogels are composed of a galactose-based shell with an inner core of thermoresponsive (di(ethylene glycol) methyl ethyl methacrylate) (DEGMA). Optimization of the nanogels led to high IAZA-loading capacity (≅80-88%) and a slow time-controlled release over 50 h. Furthermore, nanoIAZA (encapsulated IAZA) displayed superior in vitro hypoxia-selective cytotoxicity and radiosensitization in comparison to free IAZA in the head and neck (FaDu) and prostate (PC3) cancer cell lines. The acute systemic toxicity profile of the nanogel (NG1) was studied in immunocompromised mice, indicating no signs of toxicity. Additionally, growth inhibition of subcutaneous FaDu xenograft tumors was observed with nanoIAZA, demonstrating that this nanoformulation offers a significant improvement in tumor regression and overall survival compared to the control.

Polysaccharides for Medical Technology: Properties and Applications.

Over the past decade, the use of polysaccharides has gained tremendous attention in the field of medical technology. They have been applied in various sectors such as tissue engineering, drug delivery system, face mask, and bio-sensing. This review article provides an overview and background of polysaccharides for biomedical uses. Different types of polysaccharides, for example, cellulose and its derivatives, chitin and chitosan, hyaluronic acid, alginate, and pectin are presented. They are fabricated in various forms such as hydrogels, nanoparticles, membranes, and as porous mediums. Successful development and improvement of polysaccharide-based materials will effectively help users to enhance their quality of personal health, decrease cost, and eventually increase the quality of life with respect to sustainability.

Bioinspired antifouling and antibacterial polymer coating with intrinsic self-healing property.

Infections caused by biofouling have become a serious concern in the health care sector. Multifunctional coatings with antifouling and antibacterial properties are widely used to combat these biofouling related infections. However, in practice macro or micro scratches or damages can happen to the coating, which can act as an active site for microbial deposition and destroy the antifouling or antibacterial functionality of the coating. Considering this fact, we have developed an excellent biocompatible and multifunctional coating with antifouling, antibacterial and self-healing properties. In this study, prebiotic chemistry inspired self-polymerization of aminomalononitrile (AMN) was used as a primary coating layer, which acted as a primer to graft vitamin B5 analogous methacrylamide polymer poly(B5AMA) and zwitterionic compound 2-methacryloyloxyethyl phosphorylcholine (MPC) containing polymer poly (MPC-st-B5AMA) by forming strong hydrogen bonds. B5AMA having multiple polar groups in the structure acted as an intrinsic self-healing material and showed an excellent antifouling property against protein and bacteria, maintaining a good hydration layer similar to the MPC containing polymer. To impart the antibacterial property to the coating, silver nanoparticles have also been incorporated, which showed more than 90% killing efficiency against both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) bacteria with significant reduction of their adhesion on the surface. Incorporation of self-healing property into the fouling repelling and antibacterial coating can significantly extend the durability of the multifunctional coating, making it promising for biomedical applications.

Synergistic size and charge conversions of functionalized PAMAM dendrimers under the acidic tumor microenvironment.

Developing nanomedicine with highly adaptive behaviors has shown great effectiveness in cancer treatment. However, the multi-functional integration of nano-therapeutic systems inevitably leads to complexity in the structure and impairs the operational efficiency or performance. Herein, we describe a novel nano-therapeutic system, G4-AB, capable of simultaneous dual conversions of the size and charge while targeting the acidic tumor microenvironment. G4-AB, containing a hydrophobic inner cavity for doxorubicin (DOX) loading, was synthesized by modifying amine-terminated 4th-generation polyamidoamine (G4-PAMAM) dendrimers with acylsulfonamide betaine (AB). Due to the dipole-dipole interaction among the AB moieties, G4-AB self-assembles to form micellar clusters with a zwitterionic surface. Possessing an anti-fouling property and suitable size, G4-AB exhibits optimized blood circulation under physiological pH conditions. Moreover, the extracellular pH value of the tumor microenvironment (pH 6.5) can trigger the protonation of acylsulfonamide, resulting in the cationization of AB and dissociation of G4-AB into unimolecular micelles (∼12 nm) due to electrostatic repulsion. The synergistic dual conversions further ensure drug accumulation with enhanced tumor penetration and cell internalization. The in vitro and in vivo experiments demonstrate that the G4-AB-DOX nano-therapeutic system possesses better antitumor efficiency and lower toxicity than free DOX or PEGylated PAMAM.

Temperature-Responsive Aldehyde Hydrogels with Injectable, Self-Healing, and Tunable Mechanical Properties.

Injectable and self-healing hydrogels with exemplary biocompatibility and tunable mechanical properties are urgently needed due to their significant advantages for tissue engineering applications. Here, we report a new temperature-responsive aldehyde hydrogel with dual physical-cross-linked networks and injectable and self-healing properties prepared from an ABA-type triblock copolymer, poly{[FPMA(4-formylphenyl methacrylate)-co-DEGMA[di(ethylene glycol) methyl ether methacrylate]-b-MPC(2-methacryloyloxyethyl phosphorylcholine)-b-(FPMA-co-DEGMA)}. The thermoresponsive poly(DEGMA) segments drive the dehydration and hydrophobic interaction, enabling polymer chain winding as the first cross-linking network, when the temperature is raised above the critical gelation temperature. Meanwhile, the benzaldehyde groups offer physical interactions, including hydrogen bonding and hydrophobic and π-π stacking interactions as the second cross-linking network. When increasing the benzaldehyde content in the triblock copolymers from 0 to 8.2 mol %, the critical gelation temperature of the resulted hydrogels dropped from 35.5 to 19.9 °C and the mechanical modulus increased from 21 to 1411 Pa. Owing to the physical-cross-linked networks, the hydrogel demonstrated excellent injectability and self-healing properties. The cell viabilities tested from MTT assays toward both normal lung fibroblast cells (MRC-5) and cancerous cervical (HeLa) cells were found to be 100 and 101%, respectively, for varying polymer concentrations up to 1 mg/mL. The 3D cell encapsulation of the hydrogels was evaluated by a cytotoxicity Live/Dead assay, showing 92% cell viability. With these attractive physiochemical and biological properties, this temperature-responsive aldehyde hydrogel can be a promising candidate as a cell scaffold for tissue engineering.

Glycopolymer-Cell-Penetrating Peptide (CPP) Conjugates for Efficient Epidermal Growth Factor Receptor (EGFR) Silencing.

Overexpression of epidermal growth factor receptor (EGFR) is observed in multiple cancers such as colorectal, lung, and cervical solid tumors. Regulating the EGFR expression is an efficient strategy to manage these malignancies, and it can be achieved by using short interfering RNA (siRNA). Cell-penetrating peptides (CPPs) demonstrated an excellent capability to enhance the cellular uptake of siRNA, but high knockdown efficiencies have not been achieved due to endosomal entrapment. In this work, Schiff's base reaction was used to modify a block {P[LAEMA(2-lactobionamidoethyl methacrylamide)37]-b-P[FPMA(4-formyl phenyl methacrylate)2-st-DMA(N,N-dimethylacrylamide)2], P2} and two statistical [P(LAEMA23-st-FPMA3) (P3) and P(LAEMA25-st-FPMA2-st-DMA2) (P4)] aldehyde-based and galactose-based polymers, prepared via reversible addition-fragmentation chain-transfer (RAFT) polymerization. An arginine-rich peptide (ARP, KRRKRRRRRK) was used as a cell-penetrating peptide (CPP) and conjugated to the polymers via a Schiff base reaction. The resulting glycopolymer-peptide conjugates were utilized to condense the siRNA to prepare polyplexes with multivalent CPPs (MCPPs, a nanoparticle with multiple copies of the CPP) to enhance the endosomal escape. The polyplexes have different surface properties as determined by the architecture of polymers and the insertion of dimethyl amide moieties. The enhancement of cellular internalization of ARP was observed by labeling the polyplexes with fluorescein isothiocyanate (FITC)-siRNA showing a localization of polyplexes in the cytoplasm of a HeLa (cervical cancer) cell line. In the in vitro EFGR silencing study, the statistical glycopolymer-peptide (P3-P) polyplexes had superior EGFR silencing efficiency in comparison with the other polymers that were studied. Furthermore, P3-P polyplexes led to less off-targeting silencing than lipofectamine 3000. These encouraging results confirmed the potency of decorating galactose-based polymers with CPP, like ARP for their application in siRNA delivery and management of cervical carcinomas.

Cellular mechanism of action of 2-nitroimidazoles as hypoxia-selective therapeutic agents.

Solid tumours are often poorly oxygenated, which confers resistance to standard treatment modalities. Targeting hypoxic tumours requires compounds, such as nitroimidazoles (NIs), equipped with the ability to reach and become activated within diffusion limited tumour niches. NIs become selectively entrapped in hypoxic cells through bioreductive activation, and have shown promise as hypoxia directed therapeutics. However, little is known about their mechanism of action, hindering the broader clinical usage of NIs. Iodoazomycin arabinofuranoside (IAZA) and fluoroazomycin arabinofuranoside (FAZA) are clinically validated 2-NI hypoxic radiotracers with excellent tumour uptake properties. Hypoxic cancer cells have also shown preferential susceptibility to IAZA and FAZA treatment, making them ideal candidates for an in-depth study in a therapeutic setting. Using a head and neck cancer model, we show that hypoxic cells display higher sensitivity to IAZA and FAZA, where the drugs alter cell morphology, compromise DNA replication, slow down cell cycle progression and induce replication stress, ultimately leading to cytostasis. Effects of IAZA and FAZA on target cellular macromolecules (DNA, proteins and glutathione) were characterized to uncover potential mechanism(s) of action. Covalent binding of these NIs was only observed to cellular proteins, but not to DNA, under hypoxia. While protein levels remained unaffected, catalytic activities of NI target proteins, such as the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the detoxification enzyme glutathione S-transferase (GST) were significantly curtailed in response to drug treatment under hypoxia. Intraperitoneal administration of IAZA was well-tolerated in mice and produced early (but transient) growth inhibition of subcutaneous mouse tumours.

Dopamine Assisted Self-Cleaning, Antifouling, and Antibacterial Coating via Dynamic Covalent Interactions.

The rapid accumulation of dead bacteria or protein on a bactericidal surface can reduce the effectiveness of the modified surface and alter its biocidal activity by shielding the surface biocide functional groups, promoting microbial attachment and subsequent biofilm formation. Thus, the alteration of biocidal activity due to biofilm formation can cause serious trouble including severe infection or implant or medical device failure leading to death. Therefore, developing a smart self-cleaning surface is of great interest. Ideally, such a surface can not only kill the attached microbials but also release the dead cells and foulants from the surface under a particular incitement on demand. In this project, a sugar-responsive self-cleaning coating has been developed by forming covalent boronic ester bonds between catechol groups from polydopamine and a benzoxaborole pendant from zwitterionic and cationic polymers. To incorporate antifouling properties and enhance the biocompatibility of the coating, bioinspired zwitterionic compound 2-methacryloyloxyethyl phosphorylcholine (MPC) was chosen and benzoxaborole pendant containing zwitterionic polymer poly(MPC-st-MAABO) (MAABO: 5-methacrylamido-1,2-benzoxaborole) was synthesized. Additionally to impart antibacterial properties to the surface, a quaternary ammonium containing cationic polymer poly(2-(methacryloyloxy)ethyl trimethylammonium (META)-st-MAABO)) was synthesized. These synthesized polymers were covalently grafted to a polydopamine (PDA) coated surface by forming a strong cyclic boronic ester complex with a catechol group of the PDA layer endowing the surface with bacteria contact-killing properties and capturing specific protein. After the addition of cis-diol containing competitive molecules, i.e., saccharides/sugars, this boronic ester complex with a catechol group of PDA was replaced and the attached polymer layer was cleaved from the surface, resulting in the release of both absorbed protein and live/killed bacteria electrostatically attached to the polymer layer. This dynamic self-cleaning surface can be a promising material for biomedical applications avoiding the gathering of dead cells and debris that are typically encountered on a traditional biocidal surface.