Improved Rigidin-Inspired Antiproliferative Agents with Modifications on the 7-Deazahypoxanthine C7/C8 Ring Systems.

To improve their aqueous solubility characteristics, water-solubilizing groups were added to some antiproliferative, rigidin-inspired 7-deazahypoxanthine frameworks after molecular modeling seemed to indicate that structural modifications on the C7 and/or C8 phenyl groups would be beneficial. To this end, two sets of 7-deazahypoxanthines were synthesized by way of a multicomponent reaction approach. It was subsequently determined that their antiproliferative activity against HeLa cells was retained for those derivatives with a glycol ether at the 4'-position of the C8 aryl ring system, while also significantly improving their solubility behavior. The best of these compounds were the equipotent 6-[4-(2-ethoxyethoxy)benzoyl]-2-(pent-4-yn-1-yl)-5-phenyl-1,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one 33 and 6-[4-(2-ethoxyethoxy)benzoyl]-5-(3-fluorophenyl)-2-(pent-4-yn-1-yl)-1,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one 59. Similarly to the parent 1, the new derivatives were also potent inhibitors of tubulin assembly. In treated HeLa cells, live cell confocal microscopy demonstrated their impact on microtubulin dynamics and spindle morphology, which is the upstream trigger of mitotic delay and cell death.

Red-Light Activation of a Microtubule Polymerization Inhibitor via Amide Functionalization of the Ruthenium Photocage.

Photoactivated chemotherapy (PACT) is a promising cancer treatment modality that kills cancer cells via photochemical uncaging of a cytotoxic drug. Most ruthenium-based photocages used for PACT are activated with blue or green light, which penetrates sub-optimally into tumor tissues. Here, we report amide functionalization as a tool to fine-tune the toxicity and excited states of a terpyridine-based ruthenium photocage. Due to conjugation of the amide group with the terpyridine π system in the excited state, the absorption of red light (630 nm) increased 8-fold, and the photosubstitution rate rose 5-fold. In vitro, red light activation triggered inhibition of tubulin polymerization, which led to apoptotic cell death both in normoxic (21 % O2 ) and hypoxic (1 % O2 ) cancer cells. In vivo, red light irradiation of tumor-bearing mice demonstrated significant tumor volume reduction (45 %) with improved biosafety, thereby demonstrating the clinical potential of this compound.

Photothermal Modulation of Dynamic Covalent Poly(ethylene glycol)/PEDOT Composite Hydrogels for On-Demand Drug Delivery.

Hydrogels are cross-linked three-dimensional polymer networks that have tissue-like properties. Dynamic covalent bonds (DCB) can be utilized as hydrogel cross-links to impart injectability, self-healing ability, and stimuli responsiveness to these materials. In our research, we utilized dynamic thiol-Michael bonds as cross-links in poly(ethylene glycol) (PEG)-based hydrogels. Because the equilibrium of the reversible, exothermic thiol-Michael reaction can be modulated by temperature, we investigated the possibility of using thermal and photothermal stimuli to modulate the gel-to-sol transition of these materials with the aim of developing an on-demand pulsatile cargo release system. For this purpose, we incorporated poly(3,4-ethylenedioxythiophene) (PEDOT) nanoparticles within the hydrogel to facilitate photothermal modulation using near-infrared light. PEDOT nanoparticles of 50 nm in diameter and with strong near-infrared absorption were prepared by oxidative emulsion polymerization. We then used Michael addition of thiol-ene pairs from 4-arm PEG-thiol (PEG-SH) and 4-arm PEG-benzylcyanoacetamide (PEG-BCA) to form dynamically cross-linked hydrogels. PEDOT nanoparticles were entrapped in situ to form Gel/PEDOT composites. Rheology and inverted tube test studies showed that the gel-to-sol transition occurred at 45-50 °C for 5 wt % gels and that this transition could be tailored by varying the wt % of the polymer precursors. The hydrogels were found to be capable of self-healing and being injected with a clinically relevant injection force. Bovine serum albumin-fluorescein isothiocyanate (BSA-FITC), a fluorescently labeled protein, was then loaded into the Gel/PEDOT as a therapeutic mimic. Increased release of BSA-FITC upon direct thermal stimulation and photothermal stimulation with an 808 nm laser was observed. Pulsatile release of BSA-FITC over seven cycles was demonstrated. MTS and live-dead assays demonstrated that Gel/PEDOT was cytocompatible in MDA-MB-231 breast cancer and 3T3 fibroblast cell lines. Further studies demonstrated that the encapsulation and laser-triggered release of the chemotherapeutic agent doxorubicin (DOX) could also be achieved. Altogether, this work advances our understanding of the temperature-dependent behavior of a dynamic covalent hydrogel, Gel/PEDOT, and leverages that understanding for application as a photothermally responsive biomaterial for controlled release.

Design of smart nanomedicines for effective cancer treatment.

Nanomedicine is a novel field of study that involves the use of nanomaterials to address challenges and issues that are associated with conventional therapeutics for cancer treatment including, but not limited to, low bioavailability, low water-solubility, narrow therapeutic window, nonspecific distribution, and multiple side effects of the drugs. Multiple strategies have been exploited to reduce the nonspecific distribution, and thus the side effect of the active pharmaceutical ingredients (API), including active and passive targeting strategies and externally controllable release of the therapeutic cargo. Site-specific release of the drug prevents it from impacting healthy cells, thereby significantly reducing side effects. API release triggers can be either externally applied, as in ultrasound-mediated activation, or induced by the tumor. To rationally design such nanomedicines, a thorough understanding of the differences between the tumor microenvironment versus that of healthy tissues must be paired with extensive knowledge of stimuli-responsive biomaterials. Herein, we describe the characteristics that differentiate tumor tissues from normal tissues. Then, we introduce smart materials that are commonly used for the development of smart nanomedicines to be triggered by stimuli such as changes in pH, temperature, and enzymatic activity. The most recent advances and their impact on the field of cancer therapy are further discussed.

Dual Photothermal/Chemotherapy of Melanoma Cells with Albumin Nanoparticles Carrying Indocyanine Green and Doxorubicin Leads to Immunogenic Cell Death.

Recent focus on cancer immunotherapies has led to significant interest in the development of therapeutic strategies that can lead to immunogenic cell death (ICD), which can cause activation of an immune response against tumor cells and improve immunotherapy outcomes by enhancing the immunogenicity of the tumor microenvironment. In this work, a nanomedicine-mediated combination therapy is used to deliver the ICD inducers doxorubicin (Dox), a chemotherapeutic agent, and indocyanine green (ICG), a photothermal agent. These agents are loaded into nanoparticles (NPs) of bovine serum albumin (BSA) that are prepared through a desolvation process. The formulation of BSA NPs is optimized to achieve NPs of 102.6  nm in size and loadings of 8.55 % and 5.69 % (w/w) for ICG and Dox, respectively. The controlled release of these agents from the BSA NPs is confirmed. Upon laser irradiation for 2.5 min, NPs at a dose of 62.5 µg mL-1 are able to increase the temperature of the cells by 7 °C and thereby inhibit the growth of B16F10 melanoma cells in vitro. Surface presentation of heat shock proteins and calreticulin from the cells after treatment confirmed the ability of the Dox/ICG loaded BSA NPs to induce ICD in the melanoma cells.

[3 + 2]-Annulation of pyridinium ylides with 1-chloro-2-nitrostyrenes unveils a tubulin polymerization inhibitor.

Indolizines and pyrazolo[1,5-a]pyridines were prepared via [3 + 2]-cycloaddition of pyridinium ylides to 1-chloro-2-nitrostyrenes. The synthesized molecules were evaluated for antiproliferative activities against a BE(2)-C neuroblastoma cell line with several compounds decreasing the viability of cancer cells. Indolizine 9db showed higher potency than that of all-trans-retinoic acid, an approved cancer drug. Mechanistically, it was found to inhibit tubulin polymerization and it is thus proposed that the discovered chemistry can be exploited for the development of novel microtubule-targeting anticancer agents.

Laser nanobubbles induce immunogenic cell death in breast cancer.

Recent advances in immunotherapy have highlighted a need for therapeutics that initiate immunogenic cell death in tumors to stimulate the body's immune response to cancer. This study examines whether laser-generated bubbles surrounding nanoparticles ("nanobubbles") induce an immunogenic response for cancer treatment. A single nanosecond laser pulse at 1064 nm generates micron-sized bubbles surrounding gold nanorods in the cytoplasm of breast cancer cells. Cell death occurred in cells treated with nanorods and irradiated, but not in cells with irradiation treatment alone. Cells treated with nanorods and irradiation had increased damage-associated molecular patterns (DAMPs), including increased expression of chaperone proteins human high mobility group box 1 (HMGB1), adenosine triphosphate (ATP), and heat shock protein 70 (HSP70). This enhanced expression of DAMPs led to the activation of dendritic cells. Overall, this treatment approach is a rapid and highly specific method to eradicate tumor cells with simultaneous immunogenic cell death signaling, showing potential as a combination strategy for immunotherapy.

Induction of immunogenic cell death of cancer cells through nanoparticle-mediated dual chemotherapy and photothermal therapy.

The use of nanomedicines to induce immunogenic cell death is a new strategy that aims to increase tumor immunogenicity and thereby prime tumors for further immunotherapies. In this study, we developed a nanoparticle formulation for combinatory chemotherapy and photothermal therapy based only on materials previously used in FDA-approved products and investigated the effect of the combinatory therapy on the growth inhibition and induction of immunogenic cell death in human MDA-MB-231 breast cancer cells. The formulation consists of ~108-nm nanoparticles made of poly(lactic acid)-b-methoxy poly(ethylene glycol) which carry doxorubicin for chemotherapy and indocyanine green for photothermal therapy. A 0.3 mg/mL suspension of NPs increased the medium temperature up to 10 °C upon irradiation with an 808-nm diode laser. In vitro studies showed that combination of laser assisted indocyanine green-mediated photothermal therapy and doxorubicin-mediated chemotherapy effectively eradicated cancer cells and resulted in the highest level of damage-associated molecular pattern presentation (calreticulin, high mobility group box 1, and adenosine triphosphate) compared to the individual treatments alone. These results demonstrate that our nanoparticle-mediated combinatory approach led to the most intense immunogenic cell death when compared to individual chemotherapy or photothermal therapy, making it a potent option for future in vivo studies in combination with cancer immunotherapies.

High Throughput Preparation of Poly(Lactic-Co-Glycolic Acid) Nanoparticles Using Fiber Fluidic Reactor.

Polymeric nanoparticles (NPs) have a variety of biomedical, biotechnology, agricultural and environmental applications. As such, a great need has risen for the fabrication of these NPs in large scales. In this study, we used a high throughput fiber reactor for the preparation of poly(lactic-co-glycolic acid) (PLGA) NPs via nanoprecipitation. The fiber reactor provided a high surface area for the controlled interaction of an organic phase containing the PLGA solution with an aqueous phase, containing poly(vinyl alcohol) (PVA) as a stabilizer. This interaction led to the self-assembly of the polymer into the form of NPs. We studied operational parameters to identify the factors that have the greatest influence on the properties of the resulting PLGA NPs. We found that the concentration of the PLGA solution is the factor that has the greatest effect on NP size, polydispersity index (PDI), and production rate. Increasing PLGA concentration increased NP sizes significantly, while at the same time decreasing the PDI value. The second factor that was found to affect NP properties was the concentration of PVA solution, which resulted in increased NP sizes and decreased production rates. Flowrates of the feed streams also affected NP size to a lesser extent, while changing the operational temperature did not change the product's features. In general, the results demonstrate that fiber reactors are a suitable method for the large-scale, continuous preparation of polymeric NPs suitable for biomedical applications.

Photo-Uncaging of a Microtubule-Targeted Rigidin Analogue in Hypoxic Cancer Cells and in a Xenograft Mouse Model.

Marine alkaloid rigidins are cytotoxic compounds known to kill cancer cells at nanomolar concentrations by targeting the microtubule network. Here, a rigidin analogue containing a thioether group was "caged" by coordination of its thioether group to a photosensitive ruthenium complex. In the dark, the coordinated ruthenium fragment prevented the rigidin analogue from inhibiting tubulin polymerization and reduced its toxicity in 2D cancer cell line monolayers, 3D lung cancer tumor spheroids (A549), and a lung cancer tumor xenograft (A549) in nude mice. Photochemical activation of the prodrug upon green light irradiation led to the photosubstitution of the thioether ligand by water, thereby releasing the free rigidin analogue capable of inhibiting the polymerization of tubulin. In cancer cells, such photorelease was accompanied by a drastic reduction of cell growth, not only when the cells were grown in normoxia (21% O2) but also remarkably in hypoxic conditions (1% O2). In vivo, low toxicity was observed at a dose of 1 mg·kg-1 when the compound was injected intraperitoneally, and light activation of the compound in the tumor led to 30% tumor volume reduction, which represents the first demonstration of the safety and efficacy of ruthenium-based photoactivated chemotherapy compounds in a tumor xenograft.

Biomedical Application of Electroactive Polymers in Electrochemical Sensors: A Review.

Conducting polymers are of interest due to their unique behavior on exposure to electric fields, which has led to their use in flexible electronics, sensors, and biomaterials. The unique electroactive properties of conducting polymers allow them to be used to prepare biosensors that enable real time, point of care (POC) testing. Potential advantages of these devices include their low cost and low detection limit, ultimately resulting in increased access to treatment. This article presents a review of the characteristics of conducting polymer-based biosensors and the recent advances in their application in the recognition of disease biomarkers.

Microtubule-Targeting 7-Deazahypoxanthines Derived from Marine Alkaloid Rigidins: Exploration of the N3 and N9 Positions and Interaction with Multidrug-Resistance Proteins.

Our laboratories have been investigating synthetic analogues of marine alkaloid rigidins that possess promising anticancer activities. These analogues, based on the 7-deazahypoxanthine skeleton, are available in one- or two-step synthetic sequences and exert cytotoxicity by disrupting microtubule dynamics in cancer cells. In the present work we extended the available structure-activity relationship (SAR) data to N3- and N9-substituted derivatives. Although N3 substitution results in loss of activity, the N9-substituted compounds retain nanomolar antiproliferative activities and the anti-tubulin mode of action of the original unsubstituted compounds. Furthermore, our results also demonstrate that multidrug-resistance (MDR) proteins do not confer resistance to both N9-unsubstituted and -substituted compounds. It was found that sublines overexpressing ABCG2, ABCC1, and ABCB1 proteins are as responsive to the rigidin analogues as their parental cell lines. Thus, the study reported herein provides further impetus to investigate the rigidin-inspired 7-deazahypoxanthines as promising anticancer agents.

Doxorubicin-loaded protease-activated near-infrared fluorescent polymeric nanoparticles for imaging and therapy of cancer.

INTRODUCTION: Despite significant progress in the field of oncology, cancer remains one of the leading causes of death. Chemotherapy is one of the most common treatment options for cancer patients but is well known to result in off-target toxicity. Theranostic nanomedicines that integrate diagnostic and therapeutic functions within an all-in-one platform can increase tumor selectivity for more effective chemotherapy and aid in diagnosis and monitoring of therapeutic responses. MATERIAL AND METHODS: In this work, theranostic nanoparticles were synthesized with commonly used biocompatible and biodegradable polymers and used as cancer contrast and therapeutic agents for optical imaging and treatment of breast cancer. These core-shell nanoparticles were prepared by nanoprecipitation of blends of the biodegradable and biocompatible amphiphilic copolymers poly(lactic-co-glycolic acid)-b-poly-l-lysine and poly(lactic acid)-b-poly(ethylene glycol). Poly-l-lysine in the first copolymer was covalently decorated with near-infrared fluorescent Alexa Fluor 750 molecules. RESULTS: The spherical nanoparticles had an average size of 60-80 nm. The chemotherapeutic drug doxorubicin was encapsulated in the core of nanoparticles at a loading of 3% (w:w) and controllably released over a period of 30 days. A 33-fold increase in near-infrared fluorescence, mediated by protease-mediated cleavage of the Alexa Fluor 750-labeled poly-l-lysine on the surface of the nanoparticles, was observed upon interaction with the model protease trypsin. The cytocompatibility of drug-free nanoparticles and growth inhibition of drug-loaded nanoparticles on MDA-MB-231 breast cancer cells were investigated with a luminescence cell-viability assay. Drug-free nanoparticles were found to cause minimal toxicity, even at high concentrations (0.2-2,000 µg/mL), while doxorubicin-loaded nanoparticles significantly reduced cell viability at drug concentrations >10 µM. Finally, the interaction of the nanoparticles with breast cancer cells was studied utilizing fluorescence microscopy, demonstrating the potential of the nanoparticles to act as near-infrared fluorescence optical imaging agents and drug-delivery carriers. CONCLUSION: Doxorubicin-loaded, enzymatically activatable nanoparticles of less than 100 nm were prepared successfully by nanoprecipitation of copolymer blends. These nanoparticles were found to be suitable as controlled drug delivery systems and contrast agents for imaging of cancer cells.

Enhanced Release of Molecules upon Ultraviolet (UV) Light Irradiation from Photoresponsive Hydrogels Prepared from Bifunctional Azobenzene and Four-Arm Poly(ethylene glycol).

Advances in biosensors and drug delivery are dependent on hydrogels that respond to external stimuli. In this work, we describe the preparation and characterization of photoresponsive hydrogels prepared by cross-linking of di-NHS ester of azobenzoic acid and four-armed, amine-terminated poly(ethylene glycol). The porous structure and composition of the hydrogels were confirmed by scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy. The reversible photoisomerization of the azobenzene-containing hydrogel cross-linkers in the gels was confirmed by absorption spectroscopy. Specifically, the photoisomerization of the cross-linkers between their trans and cis configurations was observed by monitoring the absorbance of the hydrogels at the two characteristic peaks of azobenzene (π-π* at 330 nm and n-π* at 435 nm). The effect of photoisomerization on the hydrogel structure was investigated by microscopy. Ultraviolet (UV) irradiation-induced reduction in hydrogel size was observed, which may be a result of the inherently smaller footprint of the cis azobenzene conformation, as well as dipole-dipole interactions between the polar cis azobenzene and the polymer network. The UV-triggered reduction in hydrogel size was accompanied by enhanced release of the near-infrared fluorescent dye Alexa Fluor 750 (AF750). Enhanced release of AF750 was observed in samples irradiated with UV versus dark control. Together, these data demonstrate the potential of these systems as reversible photoresponsive biomaterials.

Undergraduate research experiences: mentoring, awareness, and perceptions-a case study at a Hispanic-serving institution.

BACKGROUND: Undergraduate research experiences (UREs) have been proposed as means to increase the retention and engagement of minority-and more specifically Hispanic-college students in science, technology, engineering, and mathematics (STEM) majors. This study explores the impact of student characteristics such as gender, classification, ethnicity, and first-generation status on UREs of STEM students through four specific constructs that current literature deem particularly important: (1) research experiences, (2) mentoring experiences, (3) awareness of research opportunities and activities, and (4) perceptions on research. These constructs are here forth referred to as Experiences, Mentoring, Awareness, and Perceptions. The study was conducted at a Hispanic-serving institution (HSI) in Texas, United States (U.S.), where the overall increase in enrollment has been driven by growth in Hispanic student numbers, reflecting the demographic shift of the state and the nation. RESULTS: Participants were recruited to be part of a STEM open house. Thirty-five students participated in the Undergraduate Research Experiences: Mentoring, Awareness, and Perceptions Survey (URE MAPS). This exploratory case study sought to look at student characteristics such as gender, classification, ethnicity, and first-generation status as predictors of UREs. Results show that classification and ethnicity student characteristics are statistically significant predictors of UREs. Although gender and first-generation status regression analysis did not show statistically significant results, crosstabulations looking at correlation among variables yield interesting results. Seven percent of the female respondents responded that they "somewhat agree" with the statement that research is a lonely activity in comparison with 23% of males. The majority (60%) of all respondents who "strongly agreed" with the statement that "research is only for future scientists" were Hispanic, indicating a need to clarify such misconceptions to encourage Hispanic student participation. Most self-identified first-generation participants, of whom 80% were female, reported awareness of faculty research activities, again pointing out gender as an important factor among students' relationship with their professors. Although less than 23% of students noted current participation in mentorship, most of those did report positive impact of this relationship on their attitude and perspective toward their major. CONCLUSIONS: Despite the small sample size and inherent bias in the characteristics of the STEM open house participants, regression analysis informed by crosstabs analysis revealed some important findings. The research suggested higher-than-expected awareness of Latinos and first-generation students of institutional research activities; however, this awareness has not translated in engagement in research activities. The data also indicates the critical need for high-impact UREs and mentorship relationships, as well as for efforts to battle student preconceptions of who can benefit from such experiences. Although this case study focused on LatinX students (LatinX is a gender-neutral term for people of Latin American heritage used in the U.S.) in the U.S., retention of historically underrepresented students in STEM disciplines is a concern shared by many countries around the world. The successful recruitment, retention, and eventual success of students in STEM degrees depend greatly on the type of pathways and support that are offered. UREs might be one of those pathways.

Conductive polymer-based nanoparticles for laser-mediated photothermal ablation of cancer: synthesis, characterization, and in vitro evaluation.

Laser-mediated photothermal ablation of cancer cells aided by photothermal agents is a promising strategy for localized, externally controlled cancer treatment. We report the synthesis, characterization, and in vitro evaluation of conductive polymeric nanoparticles (CPNPs) of poly(diethyl-4,4'-{[2,5-bis(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)-1,4-phenylene] bis(oxy)}dibutanoate) (P1) and poly(3,4-ethylenedioxythiophene) (PEDOT) stabilized with 4-dodecylbenzenesulfonic acid and poly(4-styrenesulfonic acid-co-maleic acid) as photothermal ablation agents. The nanoparticles were prepared by oxidative-emulsion polymerization, yielding stable aqueous suspensions of spherical particles of <100 nm diameter as determined by dynamic light scattering and electron microscopy. Both types of nanoparticles show strong absorption of light in the near infrared region, with absorption peaks at 780 nm for P1 and 750 nm for PEDOT, as well as high photothermal conversion efficiencies (~50%), that is higher than commercially available gold-based photothermal ablation agents. The nanoparticles show significant photostability as determined by their ability to achieve consistent temperatures and to maintain their morphology upon repeated cycles of laser irradiation. In vitro studies in MDA-MB-231 breast cancer cells demonstrate the cytocompatibility of the CPNPs and their ability to mediate complete cancer cell ablation upon irradiation with an 808-nm laser, thereby establishing the potential of these systems as agents for laser-induced photothermal therapy.

Marine Mollusk-Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance.

The chemical investigation of marine mollusks has led to the isolation of a wide variety of bioactive metabolites, which evolved in marine organisms as favorable adaptations to survive in different environments. Most of them are derived from food sources, but they can be also biosynthesized de novo by the mollusks themselves, or produced by symbionts. Consequently, the isolated compounds cannot be strictly considered as "chemotaxonomic markers" for the different molluscan species. However, the chemical investigation of this phylum has provided many compounds of interest as potential anticancer drugs that assume particular importance in the light of the growing literature on cancer biology and chemotherapy. The current review highlights the diversity of chemical structures, mechanisms of action, and, most importantly, the potential of mollusk-derived metabolites as anticancer agents, including those biosynthesized by mollusks and those of dietary origin. After the discussion of dolastatins and kahalalides, compounds previously studied in clinical trials, the review covers potentially promising anticancer agents, which are grouped based on their structural type and include terpenes, steroids, peptides, polyketides and nitrogen-containing compounds. The "promise" of a mollusk-derived natural product as an anticancer agent is evaluated on the basis of its ability to target biological characteristics of cancer cells responsible for poor treatment outcomes. These characteristics include high antiproliferative potency against cancer cells in vitro, preferential inhibition of the proliferation of cancer cells over normal ones, mechanism of action via nonapoptotic signaling pathways, circumvention of multidrug resistance phenotype, and high activity in vivo, among others. The review also includes sections on the targeted delivery of mollusk-derived anticancer agents and solutions to their procurement in quantity.

Electroactive Polymer Nanoparticles Exhibiting Photothermal Properties.

A method for the synthesis of electroactive polymers is demonstrated, starting with the synthesis of extended conjugation monomers using a three-step process that finishes with Negishi coupling. Negishi coupling is a cross-coupling process in which a chemical precursor is first lithiated, followed by transmetallation with ZnCl2. The resultant organozinc compound can be coupled to a dibrominated aromatic precursor to give the conjugated monomer. Polymer films can be prepared via electropolymerization of the monomer and characterized using cyclic voltammetry and ultraviolet-visible-near infrared (UV-Vis-NIR) spectroscopy. Nanoparticles (NPs) are prepared via emulsion polymerization of the monomer using a two-surfactant system to yield an aqueous dispersion of the polymer NPs. The NPs are characterized using dynamic light scattering, electron microscopy, and UV-Vis-NIR-spectroscopy. Cytocompatibility of NPs is investigated using the cell viability assay. Finally, the NP suspensions are irradiated with a NIR laser to determine their effectiveness as potential materials for photothermal therapy (PTT).

Biodegradable DNA-enabled poly(ethylene glycol) hydrogels prepared by copper-free click chemistry.

Significant research has focused on investigating the potential of hydrogels in various applications and, in particular, in medicine. Specifically, hydrogels that are biodegradable lend promise to many therapeutic and biosensing applications. Endonucleases are critical for mechanisms of DNA repair. However, they are also known to be overexpressed in cancer and to be present in wounds with bacterial contamination. In this work, we set out to demonstrate the preparation of DNA-enabled hydrogels that could be degraded by nucleases. Specifically, hydrogels were prepared through the reaction of dibenzocyclooctyne-functionalized multi-arm poly(ethylene glycol) with azide-functionalized single-stranded DNA in aqueous solutions via copper-free click chemistry. Through the use of this method, biodegradable hydrogels were formed at room temperature in buffered saline solutions that mimic physiological conditions, avoiding possible harmful effects associated with other polymerization techniques that can be detrimental to cells or other bioactive molecules. The degradation of these DNA-cross-linked hydrogels upon exposure to the model endonucleases Benzonase(®) and DNase I was studied. In addition, the ability of the hydrogels to act as depots for encapsulation and nuclease-controlled release of a model protein was demonstrated. This model has the potential to be tailored and expanded upon for use in a variety of applications where mild hydrogel preparation techniques and controlled material degradation are necessary including in drug delivery and wound healing systems.

Novel Microtubule-Targeting 7-Deazahypoxanthines Derived from Marine Alkaloid Rigidins with Potent in Vitro and in Vivo Anticancer Activities.

Docking studies of tubulin-targeting C2-substituted 7-deazahypoxanthine analogues of marine alkaloid rigidins led to the design and synthesis of compounds containing linear C2-substituents. The C2-alkynyl analogue was found to have double- to single-digit nanomolar antiproliferative IC50 values and showed statistically significant tumor size reduction in a colon cancer mouse model at nontoxic concentrations. These results provide impetus and further guidance for the development of these rigidin analogues as anticancer agents.