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1.
Macromol Rapid Commun ; 45(8): e2300696, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38160322

ABSTRACT

Controlling the internal structure of block copolymer (BCP) particles has a significant influence on its functionalities. Here, a structure-controlling method is proposed to regulate the internal structure of BCP Janus colloidal particles using different surfactants. Different microphase separation processes take place in two connected halves of the Janus particles. An order-order transition between gyroid and lamellar phases is observed in polymeric colloids. The epitaxial growth during the structural transformation from gyroid to lamellar phase undergoes a two-layered rearrangement to accommodate the interdomain spacing mismatch between these two phases. This self-assembly behavior can be ascribed to the preferential wetting of BCP chains at the interface, which can change the chain conformation of different blocks. The Janus colloidal particles can further experience a reversible phase transition by restructuring the polymer particles under solvent vapor. It is anticipated that the new phase behavior found in Janus particles can not only enrich the self-assembly study of BCPs but also provide opportunities for various applications based on Janus particles with ordered structures.


Subject(s)
Colloids , Polymers , Colloids/chemistry , Polymers/chemistry , Particle Size , Surface Properties , Surface-Active Agents/chemistry , Phase Transition , Molecular Structure
2.
Int J Nanomedicine ; 15: 4431-4440, 2020.
Article in English | MEDLINE | ID: mdl-32606687

ABSTRACT

INTRODUCTION: Synergistic treatment integrating photothermal therapy (PTT) and chemotherapy is a promising strategy for hepatocellular carcinoma (HCC). However, the most commonly used photothermal agent, IR820, and chemotherapeutic drug, doxorubicin hydrochloride (DOX), are both hydrophilic molecules that suffer from the drawbacks of a short circulation time, rapid elimination and off-target effects. METHODS AND RESULTS: Herein, a novel nanodrug that combined HCC-targeted IR820 and DOX was developed based on excipient-free co-assembly. First, lactosylated IR820 (LA-IR820) was designed to target HCC. Then, the LA-IR820/DOX nanodrug (LA-IR820/DOX ND) was purely self-assembled without excipient assistance. The physicochemical properties and the chemo-photothermal antitumour activity of the excipient-free LA-IR820/DOX ND were evaluated. More importantly, the obtained LA-IR820/DOX ND exhibited 100% drug loading, remarkable HCC targeting and excellent antitumour efficacy. CONCLUSION: This excipient-free LA-IR820/DOX ND may be a promising candidate for the synchronous delivery and synergistic targeting of IR820 and DOX as a combined chemo-photothermal therapy.


Subject(s)
Antineoplastic Agents/therapeutic use , Doxorubicin/therapeutic use , Indocyanine Green/analogs & derivatives , Lactose/chemistry , Animals , Antineoplastic Agents/pharmacology , Carcinoma, Hepatocellular/drug therapy , Cell Line, Tumor , Doxorubicin/chemistry , Drug Delivery Systems , Drug Liberation , Drug Synergism , Humans , Indocyanine Green/therapeutic use , Indocyanine Green/toxicity , Liver Neoplasms/drug therapy , Mice , Nanoparticles/ultrastructure
3.
J Colloid Interface Sci ; 545: 172-183, 2019 Jun 01.
Article in English | MEDLINE | ID: mdl-30878783

ABSTRACT

Graphene oxide (GO), as a drug delivery carrier, has attracted considerable attention because of its interesting properties. However, GO tends to aggregate in aqueous solution. Amphiphilic molecules are usually necessary to stabilize GO. The introduction of these non-functional macromolecules on the one hand reduces drug loading, but on the other hand may cause unpredictable side effects. This study proposes a new strategy for stabilizing GO with a functional photothermal agent, IR820 (new indocyanine green) derivative. IR820 derivative results from the conjugation of active targeted lactobionic acid (LA) with IR820 for the formation of IR820-LA. IR820-LA features central aromatic groups that can associate with the GO basal plane through π-π interactions. The flanking moiety of hydrophilic LA and sulfonic groups thus provides steric stabilization of GO in aqueous solution. Moreover, IR820-LA endows GO/doxorubicin (GO/DOX) nanovehicles with fluorescence imaging ability and actively targeted chemo-photothermal therapy. Experimental results both in vitro and in vivo have indicated its good chemo-photothermal therapeutic effect according to its active tumor targeting ability and pH-sensitive drug release characteristics. Therefore, our GO/DOX/IR820-LA nanohybrids can be excellent nanoplatforms for active tumor-targeted chemo-photothermal therapy with imaging guidance.


Subject(s)
Disaccharides/metabolism , Doxorubicin/pharmacology , Drug Carriers/chemistry , Fluorescent Dyes/chemistry , Graphite/chemistry , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Biological Transport , Cell Line, Tumor , Cell Survival/drug effects , Delayed-Action Preparations/chemistry , Doxorubicin/chemistry , Drug Liberation , Humans , Mice , Molecular Targeted Therapy/methods , Optical Imaging/methods , Particle Size , Phototherapy/methods , Surface Properties
4.
Mater Sci Eng C Mater Biol Appl ; 89: 15-24, 2018 Aug 01.
Article in English | MEDLINE | ID: mdl-29752084

ABSTRACT

Graphene oxide (GO) has shown great potential in drug delivery. However, the aqueous stability, non-specific drug release and slow release rate are major problems of the GO-based drug delivery system. Herein, we for the first time integrate the dispersant, stabilizing agent and active targeting carrier into a novel drug delivery system based on GO/PP-SS-DOX nanohybrids. The redox-sensitive PP-SS-DOX prodrug was obtained by conjugating mPEG-PLGA (PP) with doxorubicin (DOX) via disulfide bond. PEG-FA provided active targeting property for the constructed drug delivery system, GO/PP-SS-DOX/PEG-FA. In this demonstrated system, PP-SS-DOX markedly increases the stability in physiological solutions of GO and guarantees the DOX release in the reductive environment (cancerous cells). And PEG-FA helps target to cancerous tissues and induces FR-mediated endocytosis. In vitro drug release exhibited the obvious reductive sensitivity and the cumulative release amount was up to 90%, while 40% in previous reports within 72 h. The in vitro cytotoxicity of targeting nanohybrids was significantly cytotoxic than that of non-targeting nanohybrids. In vivo results displayed that the as-prepared targeting nanohybrids showed efficacious antitumor effect while it had nearly no systemic adverse toxicity on B16 tumor-bearing mice. Therefore, the in vitro and in vivo results indicate that our constructed GO/PP-SS-DOX/PEG-FA drug delivery system is a promising carrier in cancer therapy.


Subject(s)
Drug Carriers/chemistry , Graphite/chemistry , Prodrugs/chemistry , Animals , Cell Line, Tumor , Cell Survival/drug effects , Doxorubicin/chemistry , Doxorubicin/metabolism , Doxorubicin/pharmacology , Drug Liberation , Hemolysis/drug effects , Humans , Melanoma, Experimental/drug therapy , Melanoma, Experimental/pathology , Mice , Nanostructures/chemistry , Oxides/chemistry , Polyesters/chemistry , Polyethylene Glycols/chemistry , Prodrugs/metabolism , Prodrugs/pharmacology , Rabbits , Tissue Distribution
5.
J Colloid Interface Sci ; 472: 90-8, 2016 Jun 15.
Article in English | MEDLINE | ID: mdl-27016914

ABSTRACT

In this paper, we successfully synthesized folate-modified pH-sensitive copolymer methoxy-poly(ethylene glycol)2K-poly(ε-caprolactone)4K-poly(glutamic acid)1K (mPEG2K-PCL4K-PGA1K-FA), which could form the polymeric assembly in an aqueous solution, for co-delivering hydrophilic drugs doxorubicin hydrochloride (DOX) and verapamil hydrochloride (VER) (FA-poly(DOX+VER)). Since VER was an effective P-glycoprotein inhibitor, the combination of DOX and VER could reverse the multidrug resistance efficiently and enhance the therapeutic effect. Therefore, the inhibition ratios of MCF-7/ADR resistant cancer cell treated by FA-poly (DOX+VER) were almost more than 30% higher than those of FA-polyDOX after 48h and 72h. Furthermore, the conjugation of FA could lead the co-delivery systems actively targeting into the FA receptor over-expressing cancer cells in addition to the passive accumulation of the assembly in tumor tissues. Importantly, the prepared mPEG2K-PCL4K-PGA1K-FA assembly showed high pH-sensitive property, which made the drugs mostly released in tumor tissue (acid environment) than in physiological environment (neutral environment). In summary, the as-prepared co-delivery system FA-poly(DOX+VER) demonstrated a high efficiency in reversing the multidrug resistance and targeting FA receptor to improve the anticancer effect of DOX in MCF-7/ADR resistant cells.


Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors , Antibiotics, Antineoplastic/administration & dosage , Delayed-Action Preparations/chemistry , Doxorubicin/administration & dosage , Polyethylene Glycols/chemistry , Polyglutamic Acid/chemistry , Verapamil/administration & dosage , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Antibiotics, Antineoplastic/pharmacology , Doxorubicin/pharmacology , Drug Resistance, Multiple/drug effects , Drug Resistance, Neoplasm/drug effects , Humans , Hydrogen-Ion Concentration , MCF-7 Cells , Neoplasms/drug therapy , Neoplasms/metabolism , Polyesters/chemistry , Verapamil/pharmacology
6.
Chempluschem ; 81(11): 1237-1244, 2016 Nov.
Article in English | MEDLINE | ID: mdl-31964094

ABSTRACT

The objective of this study was to build mixed micelles based on two functional co-polymers, including the redox-sensitive polymer-drug conjugate methoxy poly(ethylene glycol)-poly(γ-benzyl l-glutamate)-disulfide-docetaxel (PEG-PBLG-SS-DTX) and the actively targeting methoxy poly(ethylene glycol)-folic acid (PEG-FA), for enhanced target specificity and improved anticancer efficiency of docetaxel (DTX). The spherical PEG-PBLG-SS-DTX/PEG-FA mixed micelles prepared by the dialysis method revealed a narrowly distributed size at 129.7±2.1 nm with low polydispersity of 0.10±0.02. Furthermore, the critical micelle concentration of the mixed micelles was 5.08 µg mL-1 , indicating excellent self-assembly ability in water and stability against dilution in blood circulation. The in vitro release study revealed that the conjugated DTX was rapidly released in response to dl-dithiothreitol (DTT), a reducing agent. Only 12.3 % of DTX was released from the mixed micelles after 120 h in the absence of DTT. However, the accumulative release of DTX dramatically accelerated and reached more than 40 % in 120 h after addition of DTT. The in vitro cytotoxicity, cellular uptake and cell apoptosis experiments on the mixed micelles were performed using MTT assay, fluorescence inverted microscopy and flow cytometric analysis, and 4',6-diamidino-2-phenylindole (DAPI) staining, respectively, on folate receptor (FR)-negative A549 and FR-positive MCF-7 cells. The mixed micelles could be taken up efficiently by MCF-7 cells by FR-mediated endocytosis compared with PEG-PBLG-SS-DTX micelles. Furthermore, remarkable cytotoxicity and cell apoptosis were identified for the mixed micelles against MCF-7 cells, which was consistent with the results of the cellular uptake study. On the basis of these results, the redox-sensitive PEG-PBLG-SS-DTX/PEG-FA mixed micelles using FA as a targeting ligand revealed prominent antitumor efficiency and might be a latent drug carrier for cancer chemotherapy.

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