Photodynamic therapy (PDT) is an effective non-invasive or minimally invasive treatment method against different tumors. Loading photosensitizers in nanocarriers can potentially increase their accumulation in tumor sites. However, the PDT efficacy may be hindered because of self-quenching of the encapsulated photosensitizer and the small diffusion radii of the generated reactive oxygen species (ROS). Herein, light responsive nano assemblies composed of (Polyethylene glycol)-block-poly(4,5-dimethoxy-2-nitrobenzylmethacrylate) (PEG-b-PNBMA) were designed and loaded with the photosensitizer, Rose Bengal lactone (RB), to act as a smart nanocarrier (RB-M) for the delivery of the photosensitizer. A wirelessly activated light-emitting diode (LED) implant was designed to programmatically induce the release of the loaded RB first, followed by activating PDT after diffusion of RB into the cytoplasm. The results showed that sequential '405-580 nm' irradiation of the RB-M treated 22RV1 cells resulted in the highest PDT outcome among different irradiation protocols. The combination of this smart nanocarrier and sequential '405-580 nm' irradiation strategy exhibited good PDT efficacy against 2D 22RV1 prostate cancer cells as well as 3D cancer cell spheroids. This platform overcomes the light penetration limitations in PDT, and can potentially be applied in cancer bearing patients who are unfit for chemotherapy. STATEMENT OF SIGNIFICANCE: Nanocarriers for the delivery of photosensitizer in photodynamic therapy may result in relatively low therapeutic efficacy because of self-quenching of the encapsulated photosensitizer and the small diffusion radii of the generated reactive oxygen species (ROS). Light responsive smart nanocarriers can potentially overcome this challenge. In this study, a light responsive polymer (Polyethylene glycol)-block-poly(4,5-dimethoxy-2-nitrobenzylmethacrylate) (PEG-b-PNBMA) was synthesized and utilized to fabricate the smart nanocarrier. A wirelessly activated light-emitting diode (LED) implant was designed for light delivery in deep tissue. This new approach permits wirelessly and programmatically control of photosensitizer release and PDT activation under deep tissue, thus significantly enhancing PDT efficacy against prostate cancer cells as well as 3D cancer cell spheroids. This design should have a significant impact on controllable PDT under deep tissue.

Abstract Photochemical internalization (PCI) is a promising intervention using photodynamic therapy (PDT) to enhance the activity of chemotherapeutic drugs. However, current bladder cancer treatments involve high‐dose chemotherapy and high‐irradiance PDT which cause debilitating side effects. Moreover, low penetration of light and drugs in target tissues and cumbersome light delivery procedures hinder the clinical utility of PDT and chemotherapy combination for PCI. To circumvent these challenges, a photodynamic‐chemotherapy approach is developed comprising tumor‐targeting glycosylated nanocarriers, coloaded with chlorin e6 (Ce6) and gemcitabine elaidate (GemE), and a miniaturized implantable wirelessly powered light‐emitting diode (LED) as a light source. The device successfully delivers four weekly light doses to the bladder while the nanocarrier promoted the specific accumulation of drugs in tumors. This approach facilitates the combination of low‐irradiance PDT (1 mW cm−2) and low‐dose chemotherapy (≈1500× lower than clinical dose) which significantly cures and controls orthotopic disease burden (90% treated vs control, 35%) in mice, demonstrating a potential new bladder cancer treatment option.

Current intravesical chemotherapy for non-muscle invasive bladder cancer (NMIBC) has limited efficacy due to loss of the instilled agent from urine voiding and the agent's lack of specificity for the tumors. We developed a nanocarrier (txCD47-HNP, ∼100 nm) based on human serum albumin conjugated with a peptide that targets the cluster of differentiation 47 receptor overexpressed on bladder cancer (BC) cells. The IC50 of gemcitabine elaidate (GEM) loaded in the txCD47-HNP was almost an order of magnitude lower than that of free GEM. In a mouse orthotopic BC model, GEM loaded in txCD47-HNP effectively reduced the tumor burden. Tumor cells in BC patients' urine can also be targeted by fluorescence-labeled txCD47-HNP resulting in >83 % of the cells exhibiting fluorescence. Thus, txCD47-HNP can potentially be a theranostic agent in NMIBC management by serving as a targeted drug delivery vehicle as well as an alternative to urine cytology.

Detection of non-muscle invasive bladder cancer (NMIBC) is crucial to facilitate complete tumor resection, thus improving the survival rate as well as reducing the recurrence frequency and treatment expense. Fluorescence imaging cystoscopy is an effective method for the detection of NMIBC. However, its application is limited as the commonly applied fluorescent agents such as dyes and photosensitizers usually lack specific tumor accumulation and are vulnerable to photobleaching. Furthermore, the broad emission band of conventional fluorescent agents limits their imaging and detection efficacy. To overcome these limitations, upconversion nanoparticles (UCNPs) have been selected as the fluorescent agent, due to their resistance to photobleaching, less background auto-fluorescence, and narrow emission bands. In order to achieve active tumor targeting, the UCNPs are coated with a glycosylated phospholipid layer. The glycosylated phospholipid-coated UCNPs exhibited high selective accumulation in cancer cells over normal cells and enhanced the upconversion luminescence (UCL) (at 540 nm and 660 nm) from bladder cancer cells under 980 nm laser irradiation. Glycosylated phospholipid coating that promotes uptake of UCNPs by cancer cells, and UCL emitted from UCNPs under NIR (980 nm) laser irradiation for cancer cell imaging.

One of the most detrimental consequences of surface colonization by bacteria is healthcare-associated infections (HAIs), which contribute to increased patient mortality and morbidity. Medical devices inserted into the body provide a route for bacterial migration and conducive surfaces for their attachment and proliferation. Antibacterial coatings can potentially minimize bacterial colonization and consequently reduce the occurrence of HAIs. Antibacterial coatings function by either inhibiting the attachment of bacteria (antifouling coatings) or killing bacteria attached to the surface and/or in the vicinity (bactericidal coatings). On an antifouling coating, any bacterium that manages to attach will proliferate, while on bactericidal coatings, the accumulation of dead bacteria and debris provides opportunities for other bacteria to colonize the surface. As such, the integration of antifouling and bactericidal functionalities in a single coating combines the advantages of each, increasing the probability that bacterial colonization can be successfully inhibited. This Review highlights recent developments in dual-functional polymer-based antibacterial coatings for specific biomedical applications. General strategies for endowing surfaces with either antifouling or bactericidal polymeric coatings are first discussed, followed by more detailed descriptions of coatings with integrated antifouling and bactericidal functionalities that target the important biomedical applications: blood-contacting devices, orthopedic implants, wound dressings, ocular devices, urinary catheters, endotracheal tubes, and hospital textiles. The importance of tailoring the coatings to meet the specific constraints and requirements of the intended application beyond the antibacterial functionality is emphasized, and finally, the potential challenges in translating such coatings to clinical application are highlighted.

Carbon black waste as waste by-product of oil refineries, exhibits improved specific surface area and is rich in surface functional groups after leaching. In this work, both powdered leached carbon black waste (LCBW) and LCBW-chitosan composite beads prepared via instantaneous gelation method were utilized as adsorbent to study their adsorption capabilities and behaviors for removal of tetracycline (TC) and amoxicillin (Amox) in distilled and tap water. The characterization showed that LCBW is high in specific surface area (similar to 375 m(2)/g) and contains carboxyl (-COOH) and hydroxyl (-OH) groups which are essential to the adsorption. Under the experimental conditions, adsorption capacities ranging from 12 to 205 mg/g were obtained. It was observed that the adsorption performance of powdered LCBW was enhanced by the cations presented in the tap water while the effect was insignificant to LCBW-chitosan beads. The kinetics studies showed that the adsorption of the studied antibiotics on powdered LCBW and composite beads fitted well with pseudo 1st-order and pseudo 2nd-order model, respectively. The fitting of intraparticle diffusion model showed that the adsorption process was not governed solely by intraparticle diffusion. LCBW-chitosan beads was used to investigate the continuous adsorption of TC in a fixed bed column and the experimental data was fitted to Adams-Bohart model and Thomas model.

Containment of oil spills in aquatic bodies and treatment of oily wastewater are necessary to mitigate oil pollution. Synthetic oil sorbents are commonly used for managing oil spills and while they are effective, their usage introduces a considerable amount of non-biodegradable plastic into the environment. In an effort to develop an inexpensive sorbent by reutilizing solid wastes for a sustainable future, this study investigates the fabrication of a composite oil sorbent from used polyethylene terephthalate bottles and waste carbonaceous residue from the gasification of oil refinery bottoms via an energy efficient phase inversion method. The composite sorbent demonstrated oil sorption capacity of similar to 8 g/g, which is comparable to some commercially available adsorbents, and excellent retention capacity for mineral, paraffin and crude oils of different viscosities. Furthermore, the composite is able to remove oil from mineral or paraffin oil-in-water emulsions by sorption, with an efficacy of > 99.7 %, indicating its promising application in the treatment of industrial oily wastewater. Cost analysis shows that this waste-derived composite can be produced commercially at a competitive price.

Seven patients with refractory lymphomas underwent marrow reconstitution with peripheral blood stem cells (PBSCs) harvested by large-volume leukapheresis (LVL). PBSCs were collected from all patients more than 1 month after the last cycle of chemotherapy, and no patient received growth factors. The median number of LVL procedures performed per patient was 4.5, with a mean volume of 24.5 L of blood processed per procedure to obtain 7 x 10(8) mononuclear cells per kg. Autologous PBSCs and platelets were frozen at a controlled rate in plasma and 10-percent dimethyl sulfoxide and stored in the vapor phase of liquid nitrogen. This group of patients was compared to a control group (n = 18) who received medullary marrow (MM) transplants for the same diagnoses under the same protocols during the same period. Posttransplant days to white cell engraftment (PBSC = 17, MM = 15.5) were no different. Days to platelet independence were significantly longer in the LVL PBSC group (PBSC = 33, MM = 16; p<0.05). This pattern of engraftment is typical of patients treated in this manner. Although Day 0 platelet counts (PBSC = 75.5 x 10(9)/L, MM = 85 x 10(9)/L) and total single-donor unit platelet use (PBSC = 8, MM = 9) were no different, Day 1 platelet counts (PBSC = 128 x 10(9)/L, MM = 61.5 x 10(9)/L; p<0.05) and Day 14 platelet use (PBSC = 5, MM = 8; p<0.05) were significantly different, because of the transfusion of cryopreserved autologous platelets with PBSCs on Day 0.

Bacterial colonization has detrimental consequences like hospital-associated infections, food spoilage, and equipment fouling. Antibacterial coatings can potentially be a solution, with "smart" coatings being an emerging area of interest. While the definition of smart coatings is broad, smart antibacterial coatings in this chapter are considered as those capable of exhibiting or altering their antibacterial activity in response to a stimulus. Such coatings are commonly investigated for application on medical devices, but they can potentially be applied in healthcare facilities, food packaging and textiles, and for water treatment and industrial equipment. Nevertheless, to translate these concepts into practical applications, several challenges have to be overcome such as the lack of appropriate stimuli in certain environments and the difficulty in designing coatings to control their antibacterial activity or maintain long-term efficacy. For medical-device applications the complex in vivo environment and the need to minimize toxicity pose additional challenges.

The concept of targeted drug delivery evolved from the "magic bullet" idea put forth by Paul Ehrlich more than a century ago, whose original intention was to kill disease-causing microbes without harming the body itself. In this minireview, we highlight sugar-mediated targeted delivery strategies that capitalize on the unique metabolic features of cancer cells (the so-called Warburg effect) and bacteria to enhance the efficacy of anti-cancer chemotherapeutics and antimicrobials, respectively. The differences in metabolism between cancerous and normal cells and how the overexpression of sugar transporters in cancer cells can be capitalized for cancer therapy are first discussed. Subsequently, different designs of sugar-conjugated therapeutic agents and delivery systems are presented. Finally, we show that while targeting bacterial cell metabolism to increase antimicrobial efficacy is based on a different concept from that employed for cancer therapy, co-administration of antimicrobials with glucose and other metabolites either in the free form or conjugated to carriers can increase bacterial cell susceptibility to antimicrobial agents.

Surface biofouling has been a serious environmental and ecological problem for centuries. In this study, pH-sensitive poly(2-diisopropylaminoethyl methacrylate)-b-poly(2-methacryloyl-oxyethyl phosphorylcholine) (PDPA-b-PMPC) and cationic polylysine (PLYS) chains are grafted on tannic acid (TA). The resulting PLYS-TA-PDPA-b-PMPC can be anchored in "one-step", via coordination chelation of TA, on substrate surfaces to impart the latter with switchable antimicrobial and antifouling functionalities. The PLYS-TA-PDPA-b-PMPC functionalized stainless steel (SS) surface exhibits significant antimicrobial (S. epidermidis and E. coli) activity as well as resistance to protein adsorption, bacterial adhesion, and microalgal (Amphora coffeaeformis) attachment. The reversible transition between antimicrobial and antifouling effects is achieved in response to pH changes of the surrounding environment. Decrease in pH arising from bacterial adhesion/deposition switches the antimicrobial polymer brush coatings to the antifouling mode with "self-defensive" (fouling-release/self-cleaning) capability. The functional polymer coatings exhibit low cytotoxicity. They are sustainable over 30 days of stationary exposure to filtered seawater or 14 days under flowing seawater. Therefore, the switchable antimicrobial/antifouling polymer brush coatings, with environmentally benign TA anchor and environmentally responsive fouling-release ability, are potentially useful for biofouling inhibition in biomedical and marine environments.

Surface "metallization" of poly(tetrafluoroethylene) (PTFE) film with a "synthetic metal", viz., polyaniline (PAN), was carried out chemically and physically to render the PTFE surface electrically conductive. The chemical surface modification involved the UV-induced graft copolymerization of the argon plasma-pretreated PTFE film with 4-vinylaniline (4-VAn) monomer, followed by oxidative graft copolymerization of aniline via the aniline moiety of the grafted 4-VAn polymer. The efficiency of the surface oxidative graft copolymerization with aniline (and thus the resulting surface conductivity) was enhanced by the high concentration of the grafted 4-VAn polymer from the initial graft copolymerization. The surface electrical resistance of the PTFE film so prepared was reduced by more than 10 orders of magnitude to about 106 Ω/□. The physical surface modification involved the coating of PAN on surface-modified PTFE film, prepared from UV-induced double graft copolymerization with acrylic acid (AAc) and sodium salt of styrenesulfonic acid (Na-SSAc), during the oxidative polymerization of aniline. The grafted AAc and SSAc polymers contain the protonic acid groups for the protonation/doping of the coated PAN to result in strong adhesion of the latter and a surface resistance of the PTFE film on the order of 103~104 Ω/□. The intrinsic redox states and the protonation/deprotonation behavior of the grafted and coated aniline polymer on the PTFE film were grossly similar to that of the aniline homopolymer. The surface compositions of the modified PTFE films were studied by X-ray photoelectron spectroscopy (XPS). Both the grafted and the coated aniline polymer layers exhibited good durability toward solvent extraction.

Intravesical chemotherapy for bladder cancer has limited efficacy due to the lack of specificity of drugs/drug carriers toward the cancer cells as well as inadequate drug residence time in the bladder due to urine voiding. From analyses of surface receptor expression of UMUC3 bladder cancer cells and the targeting efficacy of different peptides, we selected a peptide (txCD47) that targets the cluster of differentiation 47 (CD47) surface protein overexpressed on these cells as a targeting ligand for docetaxel (DTX) and an albumin nanocarrier of DTX. The IC50 of DTX conjugated to txCD47 (txCD47-DTX) in a 1:1 molar ratio was lowered by a factor of 3 from that of free DTX. By using the albumin molecule (txCD47-BSA) as a delivery vehicle, different amounts of txCD47 can be conjugated to investigate the effects of peptide concentration on targeting efficacy. The IC50 of DTX loaded in txCD47-BSA with 14 txCD47 per albumin molecule was 1 order of magnitude lower than that of free DTX, and a factor of 4 lower than that of txCD47-BSA with 8 txCD47 per albumin molecule. DTX was released from the albumin nanocarrier at a controlled rate, and the endocytosed carrier will release most of its payload inside the cells within 72 h. Thus, txCD47 promotes delivery of the drug/drug carrier, and the resultant enhanced killing efficacy of the drug can potentially alleviate some of the limitations of intravesical chemotherapy against bladder cancer.

Mucus is an endogenous viscoelastic biopolymer barrier that limits the entry of foreign pathogens and therapeutic carriers to the underlying mucosal cells. This could be overcome with a hydrophilic and nonpositively charged carrier surface that minimizes interactions with the mucin glycoprotein fibers. Although PEGylation remains an attractive surface strategy to enhance mucopenetration, cell uptake of PEGylated nanoparticles (NPs) often remains poor. Here, we demonstrated polydopamine (PDA) coating to enhance both mucopenetration and cell uptake of NPs. PDA was polymerized on carboxylated polystyrene (PS) NPs to form a PDA coating, and the resulting PS-PDA achieved a similar level of mucopenetration as our PEGylated PS (PS-PEG) positive control in three separate studies: NP-mucin interaction test, transwell assay, and multiple particle tracking. Compared to water, the diffusions of PS-PDA and PS-PEG in reconstituted mucus solution were only 3.5 and 2.4 times slower, respectively, whereas the diffusion of bare PS was slowed by up to 250 times. However, the uptake of PS-PDA (61.2 ± 6.1%) was almost three times higher than PS-PEG (24.6 ± 5.4%) in T24 cells, which were used as a model for underlying mucosal cells. Our results showed a novel unreported functionality of PDA coating in enhancing both mucopenetration and cell uptake of NPs for mucosal drug delivery applications, not possible with conventional PEGylation strategies.

Urine voiding and the presence of a mucus layer on the apical surface of the urothelium are two major challenges towards an effective intravesical drug delivery for bladder malignancies. Improved bioavailability to the underlying bladder tissue could be achieved with delivery vectors that diffuse efficiently through the bladder mucus. Pegylation of delivery vectors remains the existing "gold standard" to enhance mucosal delivery despite known poor cell uptake and reported PEG sensitivity. Here, we showed improved mucopenetration of carboxylated polystyrene (PS) nanoparticles (NPs) passivated with a polydopamine (PDA) surface, at similar level as PEG. While the diffusion of PS NPs in mucus was retarded by ~1000-fold, PS-PDA diffused only 6-fold slower in mucus than water. This enabled faster and deeper penetration of PS-PDA into porcine bladder tissue beneath the mucus layer. The same PDA surface also conferred biocompatibility and enabled photothermal therapy (PTT) with significant surface disruption on an ex vivo porcine bladder model upon localized laser irradiation, which was not possible with PEG. Our outcomes suggested the facile and versatile PDA surface passivation of nanoparticles as an enabler for dual purposes of enhancing mucopenetration and allowing photothermal therapy on bladder tissue, which has not been demonstrated to date.

Surface contamination by microbes leads to several detrimental consequences like hospital- and device-associated infections. One measure to inhibit surface contamination is to confer the surfaces with antimicrobial properties. Copper's antimicrobial properties have been known since ancient times, and the recent resurgence in exploiting copper for application as antimicrobial materials or coatings is motivated by the growing concern about antibiotic resistance and the pressure to reduce antibiotic use. Copper, unlike silver, demonstrates rapid and high microbicidal efficacy against pathogens that are in close contact under ambient indoor conditions, which enhances its range of applicability. This review highlights the mechanisms behind copper's potent antimicrobial property, the design and fabrication of different copper-based antimicrobial materials and coatings comprising metallic copper/copper alloys, copper nanoparticles or ions, and their potential for practical applications. Finally, as the antimicrobial coatings market is expected to grow, we offer our perspectives on the implications of increased copper release into the environment and the potential ecotoxicity effects and possibility of development of resistant genes in pathogens.

Bacterial biofilms cause chronic infections due to their inherent tolerance to antimicrobial therapies. We describe and compare the efficacy of two types of sugar (d-glucose and d-mannose)-modified cyclodextrin nanocarriers (CD-GLU and CD-MAN) loaded with antibacterial agents for preventing and eradicating bacterial biofilm. The antibacterial agents comprise a quorum sensing inhibitor (5,6-dimethyl-2-aminobenzimidazole, DMABI) and two antibiotics (erythromycin and rifampicin), and the cyclodextrin nanocarriers were tested on Pseudomonas aeruginosa (Gram-negative) and Staphylococcus aureus (Gram-positive). DMABI loaded in the CD-GLU carrier was significantly more effective at inhibiting the development of Pseudomonas aeruginosa biofilm when compared to either its free form or when it is loaded in CD without grafted sugar moieties. Antibiotics loaded in CD-GLU and CD-MAN carriers were similarly more effective at dispersing pre-formed Pseudomonas aeruginosa biofilms. These antibacterial compounds loaded in the CD-GLU and CD-MAN carriers were somewhat less effective in eradicating Staphylococcus aureus biofilm as compared to Pseudomonas aeruginosa biofilm. This difference is attributed to the different extent of penetration of the sugar-grafted carriers into the biofilms of these two species of bacterial cells. Although the sugar-grafted carrier-antibacterial agent complexes exhibit potent effects against bacterial biofilms, they are not cytotoxic to mammalian cells.

Polyphenols, the ubiquitous secondary metabolites of plants, are an important part of human diet and are essential for plant functions. They have attracted considerable interest due to their important biological activities as well as intriguing chemical and physical properties. Polyphenols allow a whole panoply of chemical and physical interactions with interesting molecules and surfaces to be established. Thus, polyphenols can serve as versatile building blocks for the preparation of various functional materials, such as capsules, antibacterial and antioxidant films, micro/nanoparticles, membranes, electronic and energy storage materials, hydrogels, and cell encapsulants, with fascinating structures and properties. In addition to their important roles in engineering of functional materials, they also emerge as pivotal components in the construction of versatile surfaces, including antifouling, antibacterial, antioxidant, cell adherent and proliferable, enzyme-immobilized, patternable and peptide-embedded surfaces. This review will describe the main interactions/reactions involving polyphenols for the design of functional materials and the construction of versatile surfaces. This review will also illustrate and discuss current applications of polyphenols in material and surface sciences.