Author Correction: pH-sensitive micelles for the intracellular co-delivery of curcumin and Pluronic L61 unimers for synergistic reversal effect of multidrug resistance.
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ABSTRACT:
SUBMITTER: Hong W
PROVIDER: S-EPMC8421502 | biostudies-literature | 2021 Sep
REPOSITORIES: biostudies-literature
Publications
Author Correction: pH-sensitive micelles for the intracellular co-delivery of curcumin and Pluronic L61 unimers for synergistic reversal effect of multidrug resistance.
Hong Wei W Shi Hong H Qiao Mingxi M Zhang Zehui Z Yang Wenting W Dong Lingying L Xie Fucheng F Zhao Chunpeng C Kang Li L
Scientific reports 20210906 1
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Project description:Pluronic L61 unimers, which are biomacromolecular modulators, and curcumin, a small-molecule modulator, were co-formulated into pH-sensitive micelles to reveal the full synergistic potential of combination drug treatments to reverse multidrug resistance (MDR). Compared to monotherapy, combined therapy significantly improved the cytotoxicity, cellular uptake and apoptotic effects of doxorubicin (DOX) against MCF-7/ADR cells. In mechanistic studies, both L61 and curcumin enhanced the cytotoxic effect by acting on mitochondrial signalling pathways. The compounds selectively accumulated in the mitochondria and disabled the mitochondria by dissipating the mitochondrial membrane potential, decreasing the ATP levels, and releasing cytochrome c, which initiated a cascade of caspase-9 and caspase-3 reactions. Furthermore, both curcumin and L61 down-regulated the expression and function of P-gp in response to drug efflux from the MCF-7/ADR cells. In the MCF-7/ADR tumour-bearing mouse model, intravenous administration of the combined therapy directly targeted the tumour, as revealed by the accumulation of DiR in the tumour site, which led to a significant inhibition of tumour growth without measurable side effects. In conclusion, co-formulation consisting of L61 and curcumin in pH-sensitive micelles induced significant synergistic effects on the reversal of MDR. Therefore, the intracellular co-delivery of various MDR modulators has great potential to reverse MDR in tumours.
| S-EPMC5307950 | biostudies-literature
Project description:BackgroundCurcumin is a natural derivative, which exhibits broad spectrum biological activities including anti-oxidant, anti-inflammatory, and anti-cancer. Since ancient times, it has been used for the treatment of various diseases. Many reports highlighted its potential as a chemopreventive and chemotherapeutic agent. Despite its imperative properties, the pharmacological application had been limited due to low solubility in the aqueous medium, limited tissue absorption, and rapid degradation at physiological pH.AimsCytotoxicity of drugs and their undesirable side effects are major obstacles in the regimens of cancer therapy. Therefore, natural plant derivatives-based anti-cancer drug delivery systems are getting more attention as they are less toxic, safer, and effective. In the present study, Pluronic block copolymer encapsulated curcumin was developed as an improved curcumin delivery system with the aim to improve its efficacy and biological response against cancer cells.Methods and resultsPluronic micelles encapsulated curcumin was synthesized, and its characterization was done by particle size analysis, Fourier transform infrared spectroscopy, small-angle neutron scattering analysis, PXRD, and differential scanning calorimetry. Further, its biological activities were corroborated in cancer cells. Results indicate that Pluronic micelles encapsulated curcumin exemplify solubility and stability of curcumin in the aqueous medium. Biophysical characterization indicated that Pluronic F127 forms nanoparticle, and its micellar core radius was increased after incorporation of curcumin. Furthermore, biological studies show that Pluronic micelles encapsulated curcumin inhibits cell proliferation, improves cellular uptake of curcumin, arrests the cell cycle in G0/G1 phase, and inhibits the activation of NF-kB and release of pro-inflammatory cytokines to manifest apoptotic cell death rather than necrotic. This formulation was non-toxic to normal cells.ConclusionThis study suggests that Pluronic micelles encapsulated curcumin is stable that can effectively inhibit cell proliferation and release of pro-inflammatory cytokines in cancer cells as compared with the free curcumin. This approach could be applied to improve the therapeutic index of anti-cancer agents.
| S-EPMC7941534 | biostudies-literature
Project description:Apart from its well-known activity as an antimicrobial agent, Curcumin (CURC) has recently started to arouse interest as a photosensitizer in the photodynamic therapy of bacterial infections. The aim of the present study was to evidence the influence of the encapsulation of Curcumin into polymeric micelles on the efficiency of photoinduced microbial inhibition. The influence of the hydrophobicity of the selected Pluronics (P84, P123, and F127) on the encapsulation, stability, and antimicrobial efficiency of CURC-loaded micelles was investigated. In addition, the size, morphology, and drug-loading capacity of the micellar drug delivery systems have been characterized. The influence of the presence of micellar aggregates and unassociated molecules of various Pluronics on the membrane permeability was investigated on both normal and resistant microbial strains of E. coli, S. aureus, and C. albicans. The antimicrobial efficiency on the common pathogens was assessed for CURC-loaded polymeric micelles in dark conditions and activated by blue laser light (470 nm). Significant results in the reduction of the microorganism's growth were found in cultures of C. albicans, even at very low concentrations of surfactants and Curcumin. Unlike the membrane permeabilization effect of the monomeric solution of Pluronics, reported in the case of tumoral cells, a limited permeabilization effect was found on the studied microorganisms. Encapsulation of the Curcumin in Pluronic P84 and P123 at very low, nontoxic concentrations for photosensitizer and drug-carrier, produced CURC-loaded micelles that prove to be effective in the light-activated inhibition of resistant species of Gram-positive bacteria and fungi.
| S-EPMC9608470 | biostudies-literature
Project description:A novel polymer-drug conjugate was prepared by the chemical reaction between the copolymer Pluronic P123 and the docetaxel via a pH sensitive hydrazone bond. These pluronic P123-docetaxel (DTX) conjugates (P123-DTX) could form the stable drug-loaded materials that can self-assemble into the defined nano-micelles in aqueous solution because of their obvious amphiphilic property and low critical micelle concentration. The spherical morphology and particle size of the prepared nano-micelles were characterized by transmission electron microscopy and dynamic light scattering, respectively. Moreover, after the introduction of pH sensitive hydrazone bond, P123-DTX micelle showed a pH dependent drug release behavior. At pH 5.0 (in 48 h), the cumulative release amount of DTX were ~84.9%, which is about six times higher than that at pH 7.4. The prepared novel p123-DTX conjugates may offer a great benefit for drug delivery and controlling the drug release.
| S-EPMC5455281 | biostudies-other
Project description:Acinetobacter baumannii is a priority bacterial pathogen and leading cause of nosocomial infections, particularly in intensive care units (ICUs). The average incidence of carbapenem-resistant A. baumannii infections in ICUs is 41.7 cases/1,000 patients, highlighting the urgent need for more effective alternative therapies to replace carbapenems. Thus, this study aimed to investigate for the first time the antibacterial activity of curcumin in combination with the novel phage vB_AbaSI_1 to combat multidrug-resistant (MDR) A. baumannii in vitro. Phage vB_AbaSI_1 (capsid diameter 91 nm, contractile tail 94/20 nm) was isolated from sewage and infects ~ 29% of the 131 bacterial isolates examined. The 52,783 kb phage genome has 75 ORFs, encodes an integrase, lacks tRNAs/virulence genes, and belongs to the Caudoviricetes. Commercially sourced curcumin (400 µg/mL), combined with phage vB_AbaSI_1 (MOI 100) reduced MDR A. baumannii 131 to undetectable levels 1 h post-treatment at 37 °C, and this efficacy was further extended for 5 h in double-dosed phage/curcumin-treated cultures. In contrast, treatment with just phage vB_AbaSI_1 reduced bacterial growth but rebounded within 3 h, while curcumin-only treated cultures showed only 1-log bacterial reduction compared to untreated control. The phage/curcumin synergy occurred exclusively with phage-susceptible strains pre-curcumin exposure. This suggests the potential disruption of bacterial cell membrane during phage infection allowing curcumin entry, as no synergy was observed with phage-resistant strains. This innovative strategy of combining phage and curcumin showed great efficacy at controlling MDR A. baumannii and has a potential for therapeutic deployment. Future work will focus on engineering the phage to make it therapeutically acceptable.
| S-EPMC11910616 | biostudies-literature
Project description: Not available
| S-EPMC11522432 | biostudies-literature
Project description:In recent years, the development of nanoreactors, such as micellar nanoreactors (MNRs) for catalytic transformations, has gained significant attention due to their potential in enhancing reaction rates, selectivity, efficiency, and, as importantly, the ability to conduct organic chemistry in aqueous solutions. Among these, the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction represents a pivotal transformation and is widely used in the synthesis of bioconjugates, pharmaceuticals, and advanced materials. This study aims toward advancing our understanding of the design and utilization of polymeric amphiphiles containing tris-triazole ligands as an integral element for CuAAC reactions within MNRs. Specifically, our investigation delves into three critical factors that influence the reaction rate within MNRs: hydrophobicity, architectural configuration of the polymeric ligands, and their concentration. Utilizing the high molecular precision of dendritic amphiphiles, we synthesized polymeric ligands with two distinct architectures, namely, PEG-ditris-triazole amphiphile (DTA) and PEG-monotris-triazole amphiphile (MTA), and explored their CuAAC reactivity through coassembly with commercially available Pluronic P123 amphiphiles. The results indicate that the architecture and the concentration of the polymeric ligands play more dominant roles in influencing the reaction rate than the hydrophobicity of the dendritic blocks. Notably, while MNRs assembled from solely DTA showed a dampened reaction rate, spiking P123 micelles with DTA yielded an MNR with significantly faster rates. Moreover, P123 MNRs spiked with the synthesized MTA demonstrated increased CuAAC reaction rates compared to those spiked with the DTA, and they even outperformed the widely used Tris(benzyltriazolylmethyl)amine ligand. These findings provide valuable insights into the design principles of polymer-based ligands for constructing reactive MNRs and other types of nanoreactors for efficient catalytic transformations.
| S-EPMC11605775 | biostudies-literature
Project description:Multidrug resistance (MDR) resulting from overexpression of P-glycoprotein (Pgp) transporters increases the drug efflux and thereby limits the chemotherapeutic efficacy. It is desirable to administer both an MDR1 gene silencer and a chemotherapeutic agent in a sequential way to generate a synergistic therapeutic effect in multidrug-resistant cancer cells. Herein, we rationally designed an anti-MDR1 molecular beacon (MB)-based micelle (a-MBM) nanosystem, which is composed of a diacyllipid core densely packed with an MB corona. One of Pgp-transportable agents, doxorubicin (DOX), was encapsulated in the hydrophobic core of the micelle and in the stem sequence of MB. The a-MBM-DOX nanosystem showed an efficient self-delivery, enhanced enzymatic stability, excellent target selectivity, and high drug-loading capacity. With its relatively high enzymatic stability, a-MBM-DOX initially facilitated intracellular MDR1 mRNA imaging to distinguish multidrug-resistant and non-multidrug-resistant cells and subsequently downregulated the MDR1 gene expression owing to an antisense effect. After that, the MB corona was degraded, destroying the micellar nanostructure and releasing DOX, which resulted in a high accumulation of DOX in OVCAR8/ADR cells and a high chemotherapeutic efficacy owing to successful restoration of drug sensitivity. This micelle approach has the potential for both visualizing MDR1 mRNA and overcoming MDR in a sequential and synergistic way.
| S-EPMC5646829 | biostudies-literature
Project description:Polyethylene glycol (PEG)-based block copolymer micelles and hyaluronic acid (HA)-based grafted copolymer micelles have been widely investigated in chemotherapy. In this study, to evaluate the differences among HA-based grafted polymer micelles, PEG-based block polymer micelles and the mixed of these two micelles in enhancing antitumor effects and overcoming MDR, two amphiphilic vitamin E succinate (VES) derivatives, HA VES (HA-g-VES) and PEG 2000 VES (TPGS2k), were applied as nanocarriers to prepare HA-VES micelles (HA-PMs), TPGS2k micelles (TPGS2k-PMs) and the mixed micelles (HA/TPGS2k-PMs) for the co-delivery of doxorubicin (DOX) and curcumin (Cur). With the addition of TPGS2k, the particle size of HA/TPGS2k-PMs (153.37 ± 1.00 nm) was smaller than that of HA-PMs (223.83 ± 1.84) but significantly larger than that of TPGS2k-PMs (about 20 nm). The loading efficiency of HA/TPGS2k-PMs was 7.10%, which was lower than HA-PMs (8.31 ± 0.15%) but higher than TPGS2k-PMs (4.38 ± 0.24%). In vitro, HA/TPGS2k-PMs and TPGS2k-PMs exhibited higher cytotoxicity and reversal MDR effects than HA-PMs in MCF-7/Adr cells. However, HA/TPGS2k-PMs, HA-PMs and TPGS2k-PMs all significantly improved the tumor biodistribution, the antitumor effects and reduced the side effects of DOX in 4T1-tumor-bearing mice, but these three micelles displayed no differences in vivo. Therefore, EPR passive targeting effects caused by PEGylated micelles and CD44 active targeting effects caused by HA-based micelles have no significant variance in the delivery of antitumor drugs by i.v.
| S-EPMC6058673 | biostudies-literature
Project description:As reported, breast cancer is one of the most common malignancies in women and has overtaken lung cancer as the most commonly diagnosed cancer worldwide by 2020. Currently, phototherapy is a promising anti-tumor therapy due to its fewer side effects, less invasiveness, and lower cost. However, its application in cancer therapeutics is limited by the incomplete therapeutic effect caused by low drug penetration and monotherapy. Herein, we built a charge-reversal nanoplatform (Ce6-PLGA@PDA-PAH-DMMA NPs), including polydopamine (PDA) and chlorin e6 (Ce6) for enhancing photothermal/photodynamic synergistic therapy. The PAH-DMMA charge-reversal layer enabled Ce6-PLGA@PDA-PAH-DMMA NPs to have long blood circulation at the normal physiological environment and to successfully realize charge reversal under the weakly acidic tumor microenvironment, improving cellular uptake. Besides, in vitro tests demonstrated that Ce6-PLGA@PDA-PAH-DMMA NPs had high photothermal conversion and greater anti-tumor activity than no charge-reversal nanoparticles, which overcame the limited tumor therapeutic efficacy of PTT or photodynamic therapy alone. Overall, the design of pH-responsive and charge-reversal nanoparticles (Ce6-PLGA@PDA-PAH-DMMA NPs) provided a promising approach for synergistic PTT/PDT therapy against breast cancer.
| S-EPMC8895045 | biostudies-literature