Chunghermansen7529

PLGA-based nanoparticles are the most studied for cancer therapy. Insufficient stability and sustained drug release, however, often lead to reduced targetability and antitumor efficacy in vivo. In this work, we report on cRGD-installed reduction-responsive cross-linked nanotherapeutics based on a star PLGA-lipoic acid conjugate (cRGD-sPLGA XNPs) for potent and targeted chemotherapy of B16F10 melanoma in mice. cRGD-sPLGA XNPs exhibited nearly quantitative encapsulation of doxorubicin (DOX), giving DOX-cRGD-sPLGA XNPs with 13.2 wt % DOX and a small size of 91.0 ± 0.6 nm. DOX-cRGD-sPLGA XNPs with a cRGD surface density of 48% exhibited the best cellular uptake in αvβ3 overexpressing B16F10 cells and delivered DOX into the cell nuclei after 6 h of incubation, in contrast to nontargeted DOX-sPLGA XNPs that delivered DOX mainly in the cytoplasm. Cell viability experiments showed that DOX-cRGD-sPLGA XNPs had about 2-fold better inhibitory activity in B16F10 cells than nontargeted DOX-sPLGA XNPs. Interestingly, DOX-cRGD-sPLGA XNPs achieved a great melanoma accumulation of 10.96% ID/g and significantly better suppression of B16F10 melanoma than DOX-sPLGA XNPs and Lipo-DOX. DOX-cRGD-sPLGA XNPs brought about marked improvement of the survival rate of B16F10 melanoma-bearing mice at 20 mg of DOX equiv/kg. Smart nanotherapeutics based on the star PLGA-lipoic acid conjugate have emerged as an appealing nanoplatform for targeted tumor therapy.Understanding the complex interplay of factors affecting nanoparticle accumulation in solid tumors is a challenge that must be surmounted to develop effective cancer nanomedicine. Among other unique microenvironment properties, tumor vascular permeability is an important feature of leaky tumor vessels which enables nanoparticles to extravasate. However, permeability has thus far been measured by intravital microscopy on optical window tumors, which has many limitations of its own. Additionally, mathematical models of particle tumor transport are often too complicated to be accessible to most researchers. Here, we present a more simplified and accessible mathematical model based on diffusive flux, which uses particle tumor accumulation and plasma pharmacokinetics to yield effective permeability, Peff. This model, called diffusive flux modeling (DFM), allows effects from multiple parameters to be decoupled and is also the first demonstration, to the best our knowledge, of extracting Peff values from bulk biodistribution results (e.g., routine positron emission tomography studies). The DFM equation was used to explain in vivo results of sub-20 nm nanocarriers called three-helix-micelles (3HM), particularly 3HM's selective accumulation in different tumor models. When DFM was applied to multiple published biodistribution data, a semiquantitative comparison of various tumor models, particle size, and active targeting strategies could be made. Akt inhibitor The analysis clearly pointed out the importance of balancing multiple characteristics of nanoparticles to ensure successful treatment outcome and highlights the usefulness of this simple model for initial particle design, selection, and subsequent optimization.Designing an extracellular matrix mimic by biofunctionalization of polymeric scaffolds is a popular strategy and extremely crucial for facilitating the interactions between cells and the matrix. To this direction, supramolecular gels are gaining exponential attention over the last few years, owing to their potential biocompatibility and biodegradability. In spite of diverse biological roles of native laminin, the bioactivities of self-assembling laminin-derived short peptides were less explored. In this work, we have explored the minimalist design to develop hydrogel scaffolds based on IKVAV and YIGSR peptides individually and their composite matrix, which can provide structurally and functionally relevant materials for tissue engineering. Till date, composite supramolecular gels solely made up of self-assembling IKVAV and YIGSR peptides have never been reported. Such composite gels can be a closer mimic of natural laminin protein, which could mimic the essential functions of the short peptide fragments presecellular functioning of the cells cultured over short laminin hydrogel scaffolds. All bioassays suggested that Fmoc YIGSR promotes growth of neural cells to a greater extent and maintains healthier morphology, in comparison to hydrophobic Fmoc IKVAV, owing to the entangled longer fibrous network formed by YIGSR peptide. It is expected that thinner long fibers provide a more uniform surface and are more supportive for cell adhesion in comparison to hydrophobic, shorter fibers IKVAV peptide. However, in composite gels, the detrimental effect of hydrophobic IKVAV peptide could be reduced and better adhesion and proliferation could be achieved along with enhanced cell survival. These observations demonstrate the high potential of the laminin-derived hydrogels in tissue engineering and neuronal stem cell differentiation in future.We have investigated the effect of piezoelectric actuating voltage on cell behavior after drop on demand inkjet printing using mouse 3T3 cells as a model cell line. Cell viability after printing was assessed using a live/dead assay, Alamar Blue as an assay for cell proliferation, and propidium iodide (PI) and Texas Red labeled dextran molecular probes to assess cell membrane integrity. No significant difference was found for the cell death rate compared between an unprinted control population and after printing at 80, 90, and 100 V, respectively. However, cell proliferation was lower than that of the control population at all time points postprinting. Cell membrane integrity was quantified using PI and dextran probes of mean molecular weight of 3, 10, 40, and 70 kDa. Total membrane damage (assessed by PI) increased with increasing piezoelectric actuator driving voltage, and this was always greater than the unprinted control cells. The uptake of the labeled dextran only occurs after inkjet printing and was never observed with the control cells. The largest dextran molecular probe of 70 kDa was only taken up by cells after printing using the lower printing voltages of 80 and 90 V and was absent after printing at 100 V. At the two lower printing voltages, the membrane damage is recovered, and no dextran molecule penetrated the cells 2 h after printing. However, printing at 100 V leads to an increased uptake of 3 and 10 kDa dextran molecules, the retention of membrane porosity, and continued uptake of these 3 and 10 kDa dextran for greater than 2 h postprinting. We hypothesize that the change in membrane porosity with increasing actuation voltage can be explained by distinct nucleation and growth stages for pore formation in response to printing stress.