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1. Implantable Cisplatin Synthesis Microdevice for Regional Chemotherapy

   https://doi.org/10.1002/adhm.202001582  

   Campbell, Rebecca; Shim, Hyunji; Choi, Je; Park, Moonchul; Byun, Eunjeong; Islam, Sayemul; Song, Seung_Hyun; Kim, Albert (December 2020, Advanced Healthcare Materials)

   Abstract Cisplatin, the first platinum chemotherapy agent to obtain Food and Drug Administration (FDA) approval in 1978, is widely used for a number of cancers. However, the painful side effects stemming from systemic delivery are the inevitable limitation of cisplatin. A possible solution is regional chemotherapy using various drug delivery systems, which reduces the systemic toxicity and increases drug accumulation in the tumor. In this paper, a rice‐grain sized, ultrasonically powered, and implantable microdevice that can synthesize cisplatin in situ is presented. The microdevice produces 0.7 mg of cisplatin within 1 h under ultrasonic irradiation (400 mW cm⁻²). The effect of the microdevice‐synthesized cisplatin is evaluated using in vitro murine breast cancer cells and ex vivo liver tissue. The results suggest that cytotoxic activities of the microdevice‐mediated cisplatin delivery are significantly higher in both in vitro and ex vivo experiments. Overall, the proposed cisplatin synthesis microdevice represents a strong alternative treatment option for regional chemotherapy 

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2. Engineering Novel Amphiphilic Platinum(IV) Complexes to Co-Deliver Cisplatin and Doxorubicin

   https://doi.org/10.3390/molecules29174095  

   Jogadi, Wjdan; Kshetri, Man B; Alqarni, Suha; Sharma, Arpit; Cheline, May; Amin, Md Al; Sheets, Cynthia; Nsoure-Engohang, Angele; Zheng, Yao-Rong (September 2024, Molecules)

   In this study, we report a novel platinum–doxorubicin conjugate that demonstrates superior therapeutic indices to cisplatin, doxorubicin, or their combination, which are commonly used in cancer treatment. This new molecular structure (1) was formed by conjugating an amphiphilic Pt(IV) prodrug of cisplatin with doxorubicin. Due to its amphiphilic nature, the Pt(IV)–doxorubicin conjugate effectively penetrates cell membranes, delivering both cisplatin and doxorubicin payloads intracellularly. The intracellular accumulation of these payloads was assessed using graphite furnace atomic absorption spectrometry and fluorescence imaging. Since the therapeutic effects of cisplatin and doxorubicin stem from their ability to target nuclear DNA, we hypothesized that the amphiphilic Pt(IV)–doxorubicin conjugate (1) would effectively induce nuclear DNA damage toward killing cancer cells. To test this hypothesis, we used flow the cytometric analysis of phosphorylated H2AX (γH2AX), a biomarker of nuclear DNA damage. The Pt(IV)–doxorubicin conjugate (1) markedly induced γH2AX in treated MDA-MB-231 breast cancer cells, showing higher levels than cells treated with either cisplatin or doxorubicin alone. Furthermore, MTT cell viability assays revealed that the enhanced DNA-damaging capability of complex 1 resulted in superior cytotoxicity and selectivity against human cancer cells compared to cisplatin, doxorubicin, or their combination. Overall, the development of this amphiphilic Pt(IV)–doxorubicin conjugate represents a new form of combination therapy with improved therapeutic efficacy. 

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3. The germline factor DDX4 contributes to the chemoresistance of small cell lung cancer cells

   https://doi.org/10.1038/s42003-023-04444-7  

   Noyes, Christopher; Kitajima, Shunsuke; Li, Fengkai; Suita, Yusuke; Miriyala, Saradha; Isaac, Shakson; Ahsan, Nagib; Knelson, Erik; Vajdi, Amir; Tani, Tetsuo; et al (January 2023, Communications Biology)

   Abstract Human cancers often re-express germline factors, yet their mechanistic role in oncogenesis and cancer progression remains unknown. Here we demonstrate that DEAD-box helicase 4 (DDX4), a germline factor and RNA helicase conserved in all multicellular organisms, contributes to increased cell motility and cisplatin-mediated drug resistance in small cell lung cancer (SCLC) cells. Proteomic analysis suggests that DDX4 expression upregulates proteins related to DNA repair and immune/inflammatory response. Consistent with these trends in cell lines, DDX4 depletion compromised in vivo tumor development while its overexpression enhanced tumor growth even after cisplatin treatment in nude mice. Further, the relatively higher DDX4 expression in SCLC patients correlates with decreased survival and shows increased expression of immune/inflammatory response markers. Taken together, we propose that DDX4 increases SCLC cell survival, by increasing the DNA damage and immune response pathways, especially under challenging conditions such as cisplatin treatment. 

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4. Effect of vortex‐induced physical stress on fluorescent properties of dye‐containing poly(ethylene glycol)‐ block‐poly (lactic acid) micelles

   https://doi.org/10.1002/app.49743  

   Odom, Tyler L.; Blankenship, Jacob R.; Campos, Giselle; Mart, Devin C.; Liu, Wenyan; Wang, Risheng; Yoshimatsu, Keiichi (July 2020, Journal of Applied Polymer Science)

   Abstract The effect of vortex‐induced mechanical stresses on the fluorescent properties of dye‐containing poly(ethylene glycol)‐block‐poly(lactic acid) (PEG‐b‐PLA) block copolymer micelles has been investigated. PEG‐b‐PLA block copolymer micelles containing fluorescent dyes, 3,3′‐dioctadecyloxacarbocyanine perchlorate (DiO) and/or 1,1′‐dioctadecyl‐3,3,3′,3′‐tetramethylindocarbocyanine perchlorate (DiI), are prepared by a simple one‐step procedure that involves the self‐assembly of block copolymers and spontaneous incorporation of hydrophobic dyes into the core of the micelles. Upon vortexing, the micelle dispersion samples showed a decrease in fluorescence intensity in a rotational speed‐ and time‐dependent manner. The results demonstrated that the vortexing can alter the fluorescent properties of the dye‐containing PEG‐b‐PLA block copolymer micelle dispersion samples, suggesting the potential utility of block copolymer micelles as a mechanical stress‐responsive nanomaterial. 

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5. Linear versus branched: flow of a wormlike micellar fluid past a falling sphere

   https://doi.org/10.1039/d1sm00281c  

   Wu, Shijian; Mohammadigoushki, Hadi (April 2021, Soft Matter)

   We report experiments on flow of wormlike micellar solutions past a falling sphere. By increasing the salt-to-surfactant concentration ratio, and beyond a viscosity peak, wormlike micelles experience a transition from linear to branched microstructure. Two viscoelastic wormlike micelles with salt to surfactant concentrations on each side of the viscosity peak are considered. Our results indicate three significant differences in flows of branched and linear micelles. First, while the sphere drag correction factor rapidly decreases upon increasing Weissenberg number in linear micelles, it shows an apparent local maximum at Wi ≈ 3 in branched micelles. Second, despite its high viscoelasticity, the time-averaged flow of branched micelles around the falling sphere exhibits a fore-and-aft symmetry, while a strong negative wake is observed in linear micelles at relatively weaker flows. Third, branched micelles exhibit a stronger flow-induced birefringence than linear micelles in an otherwise identical condition. Our hypothesis is that subject to strong flows around the falling sphere, branched micelles can relax much more efficiently than linear wormlike micelles through sliding of the branched junctions. This additional stress relaxation mechanism may facilitate micellar orientation, produce a marginal sphere drag reduction and a Newtonian-like flow profile around the falling sphere. Finally, unsteady flow is observed in both linear and branched micellar solutions beyond some critical thresholds of the extensional Weissenber number. Our results corroborate a recently proposed criterion for onset of instability in flow of wormlike micelles past a falling sphere, thereby, suggesting that micellar branching does not affect the mechanism of flow instability. 

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