Reversing the charges: Targeted charge-reversal nanoparticles (TCRNs) comprised of poly(ε-caprolactone)-block-polyethyleneimine (PCL-PEI), whose amine groups are converted into amides, negatively charged at neutral pH but become positively pH<6 (see picture). TCRNs effectively enter cells, regenerate PEI layer in lysosomes, and localize nucleus for nuclear drug delivery. Supporting information this article is available on WWW under http://www.wiley-vch.de/contents/jc_2002/2007/z605254_s.pdf...

We reexamined the cellular drug delivery mechanism by poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) to determine their utility and limitations as an intracellular system. First, we prepared PLGA NPs which physically encapsulated Nile red (a hydrophobic fluorescent dye), in accordance with usual procedure for labeling NPs, incubated them mesothelial cells, observed increase fluorescence. then from chemically conjugated a dye uptake cells using confocal microscopy. also used coherent...

The objective of these investigations was to test the hypothesis that a rapid cytoplasmic release profile from nanoparticles would potentiate anticancer activity cisplatin. Cisplatin-loaded with pH-responsive poly[2-(N,N-diethylamino)ethyl methacrylate] (PDEA) cores were synthesized PDEA-block-poly(ethylene glycol) (PDEA−PEG) copolymer by using solvent-displacement (acetone−water) method. Nanoparticles pH-nonresponsive poly(ε-caprolactone) (PCL) made PCL-block-PEG (PCL−PEG) used for...

Abstract Diabetic cardiomyopathy is manifested by compromised systolic and diastolic function. This study was designed to examine the role of advanced glycation endproduct (AGE) AGE receptor (RAGE) in diabetic cardiomyopathy. Heart function assessed isolated control streptozotocin‐induced hearts following vivo RAGE gene knockdown using RNA interference. Cardiomyocyte mechanical properties were evaluated including peak shortening (PS), time‐to‐PS (TPS) time‐to‐90% relengthening (TR 90 )....

To mimic the clinic dosing pattern, initially administering high loading dose and then low maintenance dose, we designed a novel poly(2-(pyridin-2-yldisulfanyl)ethyl acrylate) (PDS) based nanoparticle delivery system. Side chain functional PDS was synthesized by free radical polymerization. Polyethylene glycol cyclo(Arg-Gly-Asp-d-Phe-Cys) (cRGD) peptide conjugated to through thiol-disulfide exchange reaction achieve RPDSG polymer. RPDSG/DOX, loaded with doxorubicin, fabricated cosolvent...

Our previous studies demonstrated that the natural compound emodin blocks tumor-promoting feedforward interactions between cancer cells and macrophages, thus ameliorates immunosuppressive state of tumor microenvironment. Since tumor-associated macrophages (TAMs) also affect epithelial mesenchymal-transition (EMT) stem cell (CSC) formation, here we aimed to test if as a neoadjuvant therapy halts breast metastasis by attenuating TAM-induced EMT CSC formation cells. Methods: Bioinformatical...

"Stealth" nanoparticles made from polymer micelles have been widely explored as drug carriers for targeted delivery. High stability (i.e., low critical micelle concentration (CMC)) is required their intravenous applications. Herein, we present a "core−surface cross-linking" concept to greatly enhance nanoparticle's stability: amphiphilic brush copolymers form core−surface cross-linked (nanoparticles) (SCNs). The consisted of hydrophobic poly(ε-caprolactone) (PCL) and hydrophilic...

1. Cisplatin is a potent chemotherapeutic agent with broad-spectrum antineoplastic activity against various types of tumours. However, major factor limiting treatment cisplatin its acute and cumulative cardiotoxicity. The aim the present study was to explore effect on myocardial contractile function possible underlying cellular mechanisms. 2. C57 mice were treated (10 mg/kg per day, i.v.) or vehicle (0.9% NaCl) for 1 week assessed using Langendorff cardiomyocyte edge-detection systems....

Zwitterionic chitosan, a chitosan derivative with unique pH-dependent charge profile, was employed to create stealth coating on the cationic surface of drug carriers. chitosans were synthesized by amidation succinic anhydride. The anhydride-conjugated had an isoelectric point, which could be easily tuned from pH 4.9 7.1 and showed opposite charges below above point. able inhibit protein adsorption at physiological pH, compatible blood components well tolerated upon intraperitoneal injection....

Polyamidoamine (PAMAM) dendrimers with primary amine termini have been extensively explored as drug and gene carriers owing to their unique properties, but amine-carried cationic charges cause nonspecific cellular uptakes, systemic toxicity other severe problems in vivo applications.In this article, we report a charge-reversal approach that latently deactivates PAMAM's amines negatively charged acid-labile amides order inhibit its interaction cells, regenerates the active PAMAM once acidic...

Droplet microfluidics provides a high-throughput platform for screening subjects and conditions involved in biology. Droplets with encapsulated beads cells have been increasingly used studying molecular cellular sorting is needed to isolate analyze the subject of interest during such screening. The vast majority current techniques use fluorescence intensity emitted by each droplet as only criterion. However, due randomness imperfections encapsulation process, typically mixed population...

A nano cocktail, NCPD, fabricated from a pH and redox dual responsive polymer shows multicompartment structure. The NCPD nanogel is stable in physiological environments while intracellular spontaneous swelling fast releasing its payload. displays much stronger synergism than free drug counterpart, which suggests that could greatly attenuate the side effects of cocktails boosting synergistic anticancer effects. Detailed facts importance to specialist readers are published as "Supporting...

A gold/mesoporous silica hybrid nanoparticle (GoMe), which possesses the best of both conventional gold nanoparticles and mesoporous nanoparticles, such as excellent photothermal converting ability well high drug loading capacity triggerable release, has been developed. In contrast to nanorod other heat generating GoMe is stable can be repetitively activated through NIR irradiation. Doxorubicin loaded (DOX@GoMe) sensitive irradiation intracellularly elevated redox potential. DOX@GoMe coupled...

It is postulated that the complexity and heterogeneity in cancer may hinder most efforts target a single pathway. Thus, discovery of novel therapeutic agents targeting multiple pathways, such as miRNAs, holds promise for future therapy. One miRNA, miR-489, downregulated majority breast cells several drug-resistant cell lines, but its role underlying mechanism tumor suppression drug resistance needs further investigation. The current study identifies autophagy pathway targeted by miR-489...

Abstract Photothermal therapy (PTT) has attracted tremendous attention due to its noninvasiveness and localized treatment advantages. However, heat shock proteins (HSPs) associated self‐preservation mechanisms bestow cancer cells thermoresistance protect them from the damage of PTT. To minimize improve efficacy PTT, an integrated on‐demand nanoplatform composed a photothermal conversion core (gold nanorod, GNR), cargo HSPs inhibitor (triptolide, TPL), mesoporous silica based nanoreservoir,...

Abstract The biomimetic enzyme activity of cerium oxide nanoparticles (CeNPs) prefers ultrasmall particle size and bare surface. Unfortunately, those two features are not favorable for its in vivo application due to easy aggregation fast renal filtration. To take advantage the CeNP cancer therapy, a homologous targeted nanoparticle system, (T‐CeNP), with integration biodegradable dendritic mesoporous silica nanoparticle, superoxide dismutase catalase mimicking CeNPs, camouflage coating cell...

Abstract Polymer nanoparticles are extensively explored as drug carriers but they generally have issues of premature burst release, slow cellular uptake, and retention in acidic intracellular compartments. Herein, we report multifunctioning three‐layered (3LNPs) that can overcome these problems. The 3LNPs a poly(ε‐caprolactone) (PCL) core, pH‐responsive poly[2‐(N,N‐diethylamino)ethyl methacrylate](PDEA) middle layer polyethylene glycol (PEG) outer layer. PDEA is insoluble at pH above 7...

// Yogin Patel 1, 2, * , Nirav Shah Ji Shin Lee 3 Eleni Markoutsa 4 Chunfa Jie 5 Shou Liu 2 Rachel Botbyl David Reisman Peisheng Xu Hexin Chen 1 Department of Biological Science, University South Carolina, Columbia, SC, USA Center for Colon Cancer Research, Surgery, Chonnam National University, Gwangju, Republic Korea Drug Discovery and Biomedical Sciences, Carolina College Pharmacy, Master Science in Sciences Program, Des Moines Moines, IA, These authors have contributed equally to this...

Ideal "smart" nanoparticles for drug delivery should enhance therapeutic efficacy without introducing side effects. To achieve that, we developed a system (HCN) based on polymer-drug conjugate of poly[2-(pyridin-2-yldisulfanyl)]-graft-poly(ethylene glycol) and camptothecin with an intracellularly cleavable linker human epidermal growth factor receptor 2 (HER2) targeting ligands. An in vitro release study found that HCN was stable the physiological environment supersensitive to stimulus...