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1. Systemic siRNA delivery to tumors by cell-penetrating α-helical polypeptide-based metastable nanoparticles

   https://doi.org/10.1039/C8NR03976C  

   Liu, Yang ; Song, Ziyuan ; Zheng, Nan ; Nagasaka, Kenya ; Yin, Lichen ; Cheng, Jianjun ( January 2018 , Nanoscale)

   Systemic, non-viral siRNA delivery for cancer treatment is mainly achieved via condensation by cationic materials ( e.g. , lipids and cationic polymers), which nevertheless, suffers from poor serum stability, non-specific tissue interaction, and unsatisfactory membrane activity against efficient in vivo gene knockdown. Here, we report the design of a metastable, cancer-targeting siRNA delivery system based on two functional polymers, PVBLG-8, a cationic, helical cell-penetrating polypeptide, and poly( l -glutamic acid) (PLG), an anionic random-coiled polypeptide. PVBLG-8 with rigid, linear structure showed weak siRNA condensation capability, and PLG with flexible chains was incorporated as a stabilizer which provided sufficient molecular entanglement with PVBLG-8 to encapsulate the siRNA within the polymeric network. The obtained PVBLG-8/siRNA/PLG nanoparticles (PSP NPs) with positive charges were sequentially coated with additional amount of PLG, which reversed the surface charge from positive to negative to yield the metastable PVBLG-8/siRNA/PLG@PLG (PSPP) NPs. The PSPP NPs featured desired serum stability during circulation to enhance tumor accumulation via the enhanced permeability and retention (EPR) effect. Upon acidification in the tumor extracellular microenvironment and intracellular endosomes, the partial protonation of PLG on PSPP NPs surface would lead to dissociation of PLG coating from NPs, exposure of the highly membrane-active PVBLG-8, and surfacemore »charge reversal from negative to positive, which subsequently promoted tumor penetration, selective cancer cell internalization, and efficient endolysosomal escape. When siRNA against epidermal growth factor receptor (EGFR) was encapsulated, the PSPP NPs showed excellent tumor penetration capability, tumor cell uptake level, EGFR silencing efficiency, and tumor growth inhibition efficacy in U-87 MG glioblastoma tumor spheroids in vitro and in xenograft tumor-bearing mice in vivo , outperforming the PSP NPs and several commercial reagents such as Lipofectamine 2000 and poly( l -lysine) (PLL). This study therefore demonstrates a facile and unique design approach of metastable and charge reversal NPs, which overcomes multiple biological barriers against systemic siRNA delivery toward anti-cancer treatment.« less
2. Liposome Formulation for Tumor-Targeted Drug Delivery Using Radiation Therapy

   https://doi.org/10.3390/ijms231911662  

   Stolarz, Amanda J. ; Chhetri, Bijay P. ; Borrelli, Michael J. ; Jenkins, Samir V. ; Jamshidi-Parsian, Azemat ; Phillips, Joshua H. ; Fologea, Daniel ; Gandy, Jay ; Griffin, Robert J. ( October 2022 , International Journal of Molecular Sciences)

   Targeted delivery of drugs or other therapeutic agents through internal or external triggers has been used to control and accelerate the release from liposomal carriers in a number of studies, but relatively few utilize energy of therapeutic X-rays as a trigger. We have synthesized liposomes that are triggered by ionizing radiation (RTLs) to release their therapeutic payload. These liposomes are composed of natural egg phosphatidylethanolamine (PE), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and 1,2-disteroyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000] (DSPE-PEG-2000), and the mean size of the RTL was in the range of 114 to 133 nm, as measured by nanoparticle tracking analysis (NTA). The trigger mechanism is the organic halogen, chloral hydrate, which is known to generate free protons upon exposure to ionizing radiation. Once protons are liberated, a drop in internal pH of the liposome promotes destabilization of the lipid bilayer and escape of the liposomal contents. In proof of principle studies, we assessed RTL radiation-release of fluorescent tracers upon exposure to a low pH extracellular environment or exposure to X-ray irradiation. Biodistribution imaging before and after irradiation demonstrated a preferential uptake and release of the liposomes and their cargo at the site of local tumor irradiation. Finally, a potent metabolite of the commonly usedmore »chemotherapy irinotecan, SN-38, was loaded into RTL along with near infrared (NIR) fluorescent dyes for imaging studies and measuring tumor cell cytotoxicity alone or combined with radiation exposure, in vitro and in vivo. Fully loaded RTLs were found to increase tumor cell killing with radiation in vitro and enhance tumor growth delay in vivo after three IV injections combined with three, 5 Gy local tumor radiation exposures compared to either treatment modality alone.« less
3. Structure-Dependent Stability of Lipid-Based Polymer Amphiphiles Inserted on Erythrocytes

   https://doi.org/10.3390/membranes11080572  

   Yu, Chunsong ; An, Myunggi ; Li, Meng ; Manke, Charles ; Liu, Haipeng ( August 2021 , Membranes)

   Cell-based therapies have the potential to transform the treatment of many diseases. One of the key challenges relating to cell therapies is to modify the cell surface with molecules to modulate cell functions such as targeting, adhesion, migration, and cell–cell interactions, or to deliver drug cargos. Noncovalent insertion of lipid-based amphiphilic molecules on the cell surface is a rapid and nontoxic approach for modifying cells with a variety of bioactive molecules without affecting the cellular functions and viability. A wide variety of lipid amphiphiles, including proteins/peptides, carbohydrates, oligonucleotides, drugs, and synthetic polymers have been designed to spontaneously anchor on the plasma membranes. These molecules typically contain a functional component, a spacer, and a long chain diacyl lipid. Though these molecular constructs appeared to be stably tethered on cell surfaces both in vitro and in vivo under static situations, their stability under mechanical stress (e.g., in the blood flow) remains unclear. Using diacyl lipid-polyethylene glycol (lipo-PEG) conjugates as model amphiphiles, here we report the effect of molecular structures on the amphiphile stability on cell surface under mechanical stress. We analyzed the retention kinetics of lipo-PEGs on erythrocytes in vitro and in vivo and found that under mechanical stress, both the molecularmore »structures of lipid and the PEG spacer have a profound effect on the membrane retention of membrane-anchored amphiphiles. Our findings highlight the importance of molecular design on the dynamic stability of membrane-anchored amphiphiles.« less
4. Comparison of endothelial cell attachment on surfaces of biodegradable polymer-coated magnesium alloys in a microfluidic environment

   https://doi.org/10.1371/journal.pone.0205611  

   Liu, Lumei Liu ; Ye, Sang-Ho ; Gu, Xinzhu ; Russel, Teal ; Xu, Zhigang ; Wagner, William R. ; Lee, Young-Choon ( October 2018 , PloS one)

   Polymeric coatings can provide temporary stability to bioresorbable metallic stents at the initial stage of deployment by alleviating rapid degradation and providing better interaction with surrounding vasculature. To understand this interfacing biocompatibility, this study explored the endothelial-cytocompatibility of polymer-coated magnesium (Mg) alloys under static and dynamic conditions compared to that of non-coated Mg alloy surfaces. Poly (carbonate urethane) urea (PCUU) and poly (lactic-co-glycolic acid) (PLGA) were coated on Mg alloys (WE43, AZ31, ZWEKL, ZWEKC) and 316L stainless steel (316L SS, control sample), which were embedded into a microfluidic device to simulate a vascular environment with dynamic flow. The results from attachment and viability tests showed that more cells were attached on the polymer-coated Mg alloys than on non-coated Mg alloys in both static and dynamic conditions. In particular, the attachment and viability on PCUU-coated surfaces were significantly higher than that of PLGA-coated surfaces of WE43 and ZWEKC in both static and dynamic conditions, and of AZ31 in dynamic conditions (P<0.05). The elementary distribution map showed that there were relatively higher Carbon weight percentages and lower Mg weight percentages on PCUU-coated alloys than PLGA-coated alloys. Various levels of pittings were observed underneath the polymer coatings, and the pittings were more severemore »on the surface of Mg alloys that corroded rapidly. Polymer coatings are recommended to be applied on Mg alloys with relatively low corrosion rates, or after pre-stabilizing the substrate. PCUU-coating has more selective potential to enhance the biocompatibility and mitigate the endothelium damage of Mg alloy stenting.« less
5. Lab-Controlled Experimental Evaluation of Heat-Reflective Coatings by Increasing Surface Albedo for Cool Pavements in Urban Areas

   https://doi.org/doi.org/10.3390/coatings12010007  

   Lu, Yang ; Rahman, Md Asif ; Moore, Nicholas W. ; Golrokh, Aidin J. ( December 2021 , Coatings)

   Many studies were conducted to find possible strategies for reducing the urban heat island (UHI) effect during the hot summer months. One of the largest contributors to UHI is the role that paved surfaces play in the warming of urban areas. Solar-reflective cool pavements stay cooler in the sun than traditional pavements. Pavement reflectance can be enhanced by using a reflective surface coating. The use of heat-reflective coatings to combat the effects of pavements on UHI was pre-viously studied but no consistent conclusions were drawn. To find a conclusive solution, this work focuses on the abilities of heat-reflective pavement coatings to reduce UHI in varying weather conditions. Within this context, both concrete and asphalt samples were subject to a series of per-formance tests when applied to a heat-reflective coating, under the influence of normal, windy, and humid conditions. During these tests, the samples were heated with a halogen lamp and the surface temperature profile was measured using an infrared thermal camera. The air temperature was recorded with a thermometer, and the body temperature at multiple depths of the samples was measured using thermocouples. The results from these tests show that the effectiveness of the heat-reflective coating varies under different weathermore »conditions. For instance, the coated samples were about 1 °C cooler for concrete and nearly 5 °C cooler for asphalt, on average. However, this temperature difference was reduced significantly under windy conditions. As such, the findings from this work conclude that the heat-reflective coatings can effectively cool down the pavement by increasing the surface albedo, and thus might be a viable solution to mitigate UHI impacts in the city/urban areas.« less