JOURNAL OF NANOPARTICLE RESEARCH
·
2017
·Vol. 19
·期 6
·1-13
·
IF 2.02
Zhang Ran,Wang Shi-Bin,Wu Wen-Guo,Kankala Ranjith Kumar,Chen Ai-Zheng,Liu Yuan-Gang,Fan Jing-Qian
Recently, targeted drug delivery systems (TDDS) have offered a great potential and benefits towards the anti-tumor drug delivery. In this work, we designed the TDDS using a biocompatible poly(ethylene glycol)-poly( β -amino esters) amphiphilic block copolymer (PEG-PAEs) synthesized by Michael addition polymerization for combinatorial therapy. Further, the chemotherapeutic agents’ doxorubicin (DOX) and AS1411 DNA aptamer (Apt) are encapsulated in the PEG-PAEs NPs (PDANs) for co-delivery therapeutics. PDANs have shown the monodisperse spherical shape, smooth surface with a net positive charge (average diameter—183.1 ± 27.2 nm, zeta potential—31.2 ± 6.3 mV), and good colloidal stability (critical micelle concentration of PEG-PAEs is about 6.3 μg/mL). The pH-sensitive PAEs endowed PDANs both pH-triggered drug release characteristics and enhanced endo/lysosomal escape ability, thus improving the localization and cytotoxicity of DOX. AS1411 Apt conjugated PDANs precisely targeted nucleolin and their uptake correlates to a significant activity enhancement only in tumor cells (MCF-7) but not in normal cells (MCF-10A). Thus, PDANs can be a very promising targeted drug delivery platform for effective breast cancer therapy.
Scheme 1 Schematic illustration of the preparation and cellular uptake of targeted co-delivery system
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ACS Applied Materials & Interfaces
·
2017
·
IF 7.504
Haoquan Zhong,Chunchen Liu,Wenjiao Ge,Runcang Sun,Fei Huang,Xiaohui Wang
A fluorescent “turn-on” sensor for fast measurement of aliphatic biogenic amines (BAs) was developed based on fluorescent carboxylated polyfluorene (PFTBTCOOH)/chitosan-graft-oleic acid (CS-graft-OA) micelles. In this system, biobased CS-graft-OA micelles, prepared by graft modification of CS with OA, serve as the vector of the hydrophobic fluorescent probe. Bright turn-on fluorescence was achieved by the intermolecular fluorescence resonance energy transfer of the encapsulated PFTBTCOOH, driven by the formation of an electrostatic complex with aliphatic BAs, which facilitate visual identification. The peak intensity ratio of the PFTBTCOOH/CS-graft-OA micelles toward an increasing amount of aliphatic BAs was calibrated, giving a linear relationship. The fluorescence response of PFTBTCOOH/CS-graft-OA micelles to aliphatic BAs in milk and yogurt matrixes reaches a detection concentration as low as 10 μM, showing that the PFTBTCOOH/CS-graft-OA micelle solution is a potential chemosensor for fast and selective detection of trace aliphatic BAs, which is of great significance to public health and food safety.
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Biomedical Materials
·
2024
·Vol. 19
·期 2
·025021
·
IF 3.9
Peng Ding,Xiaoyue Ding,Jingyu Li,Wei Guo,Oseweuba Valentine Okoro,Mahta Mirzaei,Yanfang Sun,Guohua Jiang,Amin Shavandi,Lei Nie
The increased demand for improved strategies for wound healing has, in recent years, motivated the development of multifunctional hydrogels with favorable bio-compatibility and antibacterial properties. To this regard, the current study presented the design of a novel self-healing composite hydrogel that could perform as wound dressing for the promotion of wound healing. The composite hydrogels were composed of polyvinyl alcohol (PVA), borax and chitosan functionalized with sialic acid (SA-CS) and curcumin loaded pluronic F127 micelles. The hydrogels were formed through the boronic ester bond formation between PVA, SA-CS and borax under physiological conditions and demonstrated adjustable mechanical properties, gelation kinetics and antibacterial properties. When incubating with NIH3T3 cells, the hydrogels also demonstrated good biocompatibility. These aspects offer a promising foundation for their prospective applications in developing clinical materials for wound healing.
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International Journal of Nanomedicine
·
2024
·
IF 6.6
Xuliang Guo,Lefei Han,Wenyu Chen,Huixin He,Weijin Zhang,Chaoqi Huang,Xiu Wang
Introduction Combination therapy provides better outcomes than a single therapy and becomes an efficient strategy for cancer treatment. In this study, we designed a hypoxia- and singlet oxygen-responsive polymeric micelles which contain azo and nitroimidazole groups for enhanced cellular uptake, repaid cargo release, and codelivery of photosensitizer Ce6 and hypoxia-activated prodrug tirapazamine TPZ (DHM-Ce6@TPZ), which could be used for combining Ce6-mediated photodynamic therapy (PDT) and PDT-activated chemotherapy to enhance the therapy effect of cancer.Methods The hypoxia- and singlet oxygen-responsive polymeric micelles DHM-Ce6@TPZ were prepared by film hydration method. The morphology, physicochemical properties, stimuli responsiveness, in vitro singlet oxygen production, cellular uptake, and cell viability were evaluated. In addition, the in vivo therapeutic effects of the micelles were verified using a tumor xenograft mice model.Results The resulting dual-responsive micelles not only increased the concentration of intracellular photosensitizer and TPZ, but also facilitated photosensitizer and TPZ release for enhanced integration of photodynamic and chemotherapy therapy. As a photosensitizer, Ce6 induced PDT by generating toxic singlet reactive oxygen species (ROS), resulting in a hypoxic tumor environment to activate the prodrug TPZ to achieve efficient chemotherapy, thereby evoking a synergistic photodynamic and chemotherapy therapeutic effect. The cascade synergistic therapeutic effect of DHM-Ce6@TPZ was effectively evaluated both in vitro and in vivo to inhibit tumor growth in a breast cancer mice model.Conclusion The designed multifunctional micellar nano platform could be a convenient and powerful vehicle for the efficient co-delivery of photosensitizers and chemical drugs for enhanced synergistic photodynamic and chemotherapy therapeutic effect of cancer.
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FOOD CHEMISTRY
·
2024
·
IF 8.5
Shen Long,Meng-Jie Yu,Ran Feng,Han Tao,Bao Zhang
In this study, a novel dextrin-based micelle (OSAD-SH), dual-modified with octenyl succinic anhydride (OSA) and cysteamine, has been developed to address the acid instability issues of micelles modified only by OSA and designed for curcumin delivery. The chemical structure of OSAD-SH was characterized and the physical properties of the micelles were evaluated. Results displayed that OSAD-SH micelles exhibit strong self-assembly properties, appearing as spheres with diameters ranging from 92.41 to 194.20 nm. Blank micelles with good dilution resistance, acid, thermal, and ionic strength stability. The curcumin encapsulated by the micelles is in an amorphous state. In vitro release experiments demonstrated that curcumin released from OSAD-SH micelles exhibits intestinal targeting. The Ritger-Peppas model effectively predicted the release behavior of curcumin, indicating that the release mechanism follows super case-II transport. The OSAD-SH micelle could be a promising nanocarrier for improving the physicochemical properties of curcumin in food fields.
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Journal of Biomedical Nanotechnology
·
2017
·Vol. 13
·期 12
·1631-1646
·
IF 4.521
Wang Jiao,Liu Qiang,Yang Linnan,Xia Xiaofei,Zhu Rongrong,Chen Shengguang,Wang Mei,Cheng Liming,Wu Xianzheng,Wang Shilong
Cervical cancer is the fourth most common cancer in women worldwide, and existing treatments cause severe side effects and great burdens. Thus, the development of safe, inexpensive therapeutic agents is necessary. Curcumin (Cur), a well-known natural product, exerts promising anti-cancer
activities against various cancer types. However, its therapeutic efficacy is severely restrained due to rapid degradation, poor aqueous solubility, and low bioavailability. The objective of this study was to investigate the therapeutic potential of novel curcumin-loaded TPGS/F127/P123 mixed
polymeric micelles (Cur@NPT100) for cervical cancer treatment. The Cur@NPT100 exhibited an average size of approximately 19 nm, a zeta potential of around –4 mV, a drug loading of 8.18 ± 0.36%, and an encapsulation efficiency of 79.38 ± 4.65%. Unlike free Cur, Cur@NPT100
are readily dispersed in aqueous medium, showing enhanced stability and a sustained release profile over a 6-day period. In vitro cell culture experiments revealed that TPGS/F127/P123 mixed polymeric micelles (NPT100) based nanocarriers substantially promoted the selective cellular
uptake of Cur into HeLa cells rather than by non-cancerous NIH3T3 cells, inducing higher cytotoxicity and greater apoptosis and significantly increasing the percentage of cells arrested at the G2/M phase of the cell cycle. Additionally, the Cur@NPT100 facilitated more Cur accumulation in the
mitochondria and decreased the mitochondrial membrane potential. In addition, western blot assays demonstrated that Cur@NPT100 were more potent than free Cur at activating the mitochondria-mediated apoptosis pathway. In vivo results further confirmed that Cur@NPT100 exhibited a much higher
antitumor efficacy than free Cur and had excellent biocompatibility. In conclusion, Cur@NPT100 might be an effective therapeutic agent for cervical cancer.
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Journal of Materials Chemistry B
·
2018
·Vol. 6
·期 5
·789-796
·
IF 4.776
Lijuan Sun,Tian Qiu,Jiangxin Liu,Ke Miao,Youliang Zhao,Li-Juan Fan
The combination of fluorescence properties and other functions can significantly enhance the multipurpose applications of functional materials. Herein, fluorescent microspheres with strong fluorescence and bioconjugation sites were prepared via the layer-by-layer (LBL) introduction of poly(p-phenylene vinylene) (PPV) with micelles as a spacer on the substrate spheres. At first, the diblock copolymer poly(acrylic acid)-block-polystyrene (PAA-b-PS) was synthesized and assembled into micelles (PSAm) with the carboxylic groups facing outward. Then, the negatively charged PSAm and positively charged PPV polymer precursor (pre-PPV) were alternately introduced into the substrate polystyrene-divinylbenzene microspheres with sulfonic groups on the surface (SPSDVB) followed by thermal elimination to obtain fluorescent SPSDVB-(PPV/PSAm)n microspheres by converting pre-PPV into PPV. The spheres were found to have stable and bright fluorescence with a very clear core–shell structure. The mechanism for fluorescence enhancement with PSAm as the spacer was studied, and the capability for bioconjugation was also demonstrated. This study provides a promising general strategy for the preparation of fluorescent microspheres combining strong emission with different functional groups to meet various applications.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Fang Xie,Xiaoqing Liu,Nian Liu,Xiaofang Feng,Zhijun He,Zia-ud Din,Shuiyuan Cheng,Yangchao Luo,Jie Cai
To develop a promising selenium supplement that overcomes the instability and poor water dispersibility of selenium nanoparticles (SeNPs), we synthesized a series of amphiphilic octenyl succinic anhydride starch (OSAS) through esterification. As the degree of substitution ( DS ) increased, the particle size of OSAS micelles and the critical micelle concentration (CMC) decreased. FTIR and XRD analysis confirmed the successful introduction of octenyl succinic anhydride groups onto starch. Subsequently, OSAS micelles were used as carriers to synthesize SeNPs via in situ chemical reduction, forming SeNPs-loaded self-assembled starch nano-micelles (OSAS-SeNPs). The OSAS-SeNPs exhibited spherical dispersion in water with an average diameter of 116.1 ± 2.3 nm, contributed to enhanced hydrophobic interactions. TEM images showed a core-shell structure with SeNPs as the core and OSAS as the shell. FTIR results indicated hydrogen bonding interactions between OSAS and SeNPs. Due to the negatively charged OSAS shell and hydrogen bonding (O H⋯Se), OSAS-SeNPs remained non-aggregated for one month at room temperature, demonstrating remarkable stability. This study suggests that using OSAS can address the synthesis and stability issues of SeNPs, making it a potential selenium supplement candidate for further evaluation as an anticancer agent.
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MOLECULES
·
2024
·Vol. 29
·期 21
·5070
·
IF 4.2
Yupeng Bi,Longlong Li,Jin Liu,Yao Wang,Boying Wang,Yanxin Wang,Christopher D. Snow,Jun Li,Matt J. Kipper,Laurence A. Belfiore,Jianguo Tang
To avoid the critical problems of effective drugs not being carried to their targeted cancers and their quantity and location not being sensed in situ, this work presents a completely new innovative strategy to achieve both smart cancer targeting (SCT) and super-sensitive sensing (SSS), where one drug carrier works for effective drug loading and release. Herein, malignant melanoma treatment is used as an example of reliable detection and effective therapy. We report two characteristic dumbbell-like nano-micelles and spherical-like nano-micelles of hyaluronan induced by the Eu3+/Tb3+complexes for effective drug loading and release, respectively. These special Eu3+/Tb3+-loaded nano-micelles (marked as ENM and TNM) have strong and sharp red/green luminescence that can sensitively detect the malignant melanoma drug dacarbazine through changes in fluorescence intensity. Cytotoxicity experiments confirmed that both ENM and TNM are not toxic to normal cells at very high concentrations of 4 mM. However, when loaded with cancer drugs (D-ENM and D-ENM), they both killed cancer cells with more than 40% efficacy at this concentration. The in vivo experiments confirmed that D-ENM and D-TNM can effectively target cancer cells in tissue and effectively impede cancer growth. The detection limits of ENM and TNM in sensing cancer drugs can reach 0.456 μg/mL and 0.139 μg/mL, respectively. Therefore, the reported Eu3+/Tb3+-induced hyaluronan nano-micelles (ENM and TNM) are distinguished carriers of this cancer drug and excellent in situ sensors, and they have highly therapeutic effects with extremely low toxicity to normal cells.
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Acta Biomaterialia
·
2025
·
IF 9.6
Taotao Li,Mingzhen Cai,Qianqian Qiao,Wenjie Shi,Xin Guo,Shaoqun Tang,Xulin Jiang
Postoperative pain is a major clinic challenge and local anesthetics are preferred for use in postoperative pain management, but their short duration of analgesia limits their clinical use. Various drug carriers such as liposomes or nano/microparticles have been developed for prolonging the analgesic duration, yet how to achieve effective drug loading without using organic solvents and sustained-release local anesthetics remains a big challenge. Herein, we synthesized a pH-sensitive and biodegradable polymer to efficiently load ropivacaine (Rop-micelles) by pH-induced micellization method without using any organic solvent, avoiding the aggregation and precipitation of Rop under neutral conditions within 7 days. Subsequently, an injectable dispersion of Rop-micelles in hydroxypropyl chitin (Rop-micelles@HPCH) was developed for long-term local anesthesia. This system was prepared via a simple and solvent-free process that combined pH-sensitive micelles with thermosensitive HPCH, demonstrating proven biocompatibility and biodegradability. Importantly, the obtained Rop-micelles@HPCH composite hydrogel exhibited a much more sustained Rop release than that of drug loaded in micelles or hydrogel alone in vitro. The effective analgesic time of Rop-micelles@HPCH (20.3 h) or Rop-micelles@HPCH-Dex with only a small fraction (
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Biomaterials Science
·
2020
·Vol. 8
·期 18
·5029-5046
·
IF 6.183
Yuanhang Zhou,Chuhang Zhou,Yang Zou,Yao Jin,Shidi Han,Qi Liu,Xinping Hu,Leqi Wang,Yining Ma,Yan Liu
Combination therapy has been proved to be an effective strategy to inhibit metastasis, however, its efficacy is always compromised by the poor delivery efficiency of drugs. In this study, multi pH-sensitive polymer–drug conjugate mixed micelles were fabricated by the self-assembly of PEOz-PLA-ace-Cur, a conjugate of curcumin (Cur) with poly(2-ethyl-2-oxazoline)-poly(D,L-lactide) (PEOz-PLA) through the linkage of the pH-cleavable acetal bond, and PEOz-PLA-imi-DOX, a conjugate of doxorubicin (DOX) with PEOz-PLA through the linkage of the pH-cleavable benzoic imine bond. The mixed conjugate micelles (PP-Cur/PP-DOX-Mix-PMs) with accurately and conveniently controlled mass ratio of the two drugs were demonstrated to have a small particle size (40–128 nm), high drug loading capacity and pH-dependent drug release behavior. Notably, PP-Cur5/PP-DOX1-Mix-PMs exhibited slower DOX release under physiological conditions compared with PEOz-PLA-imi-DOX micelles, resulting in deeply reduced side effects in vivo. Furthermore, the mixed conjugate micelles showed synergistically enhanced inhibition of MDA-MB-231 cell growth and metastasis evidenced by the results of in vitro anti-invasion, wound healing and anti-migration assessment, and in vivo bioluminescence imaging in nude mice, and significant reduction of the side effects of DOX compared with dual drug physically loaded polymeric micelles. Mechanistic studies demonstrated that the possible inhibitory mechanism of PP-Cur5/PP-DOX1-Mix-PMs on tumor metastasis could be assigned to their inhibition of the invasion, migration, intravasation and extravasation of tumor cells. In conclusion, the multi pH-sensitive polymer–drug conjugate mixed micelles with synergistically enhanced anti-tumor and anti-metastasis activity are potential candidates for safe and effective cancer combination therapy.
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Polymer Chemistry
·
2014
·Vol. 6
·期 9
·1454-1464
·
IF 5.368
Qinglai Yang,Changyu He,Yuhong Xu,Bingya Liu,Zhifeng Shao,Zhenggang Zhu,Yongtai Hou,Bing Gong,Yu-Mei Shen
A folic acid (FA) conjugated chitosan oligosaccharide (CSO) polylactic acid (PLA) copolymer FA-CSO-PLA with double disulphide linkage in the backbone directed by H-bonding association duplex was synthesized, and its self-assembled micelles were evaluated as smart targeted drug delivery carriers. Both of the intermediates and the terminal copolymers were characterized by 1H-NMR and gel permeation chromatography (GPC). The critical micelle concentration (CMC) value is 0.045 mg mL−1 which suggests the micelles are highly stable in dilute solution. TEM and DLS further confirmed the successful formation of micelles with an average size of 61 and 100 nm, PDI of 0.209 and 0.230 for blank and DOX loaded micelles, respectively. The micelles were destructed under a reductive environment, leading to encapsulated drug release. Moreover, fluorescence microscopy demonstrated that the micelles exhibited both a passive and active targeting ability in HeLA cells due to an EPR effect and folate-mediated endocytosis. These results suggested the micelles would provide a favourable platform for constructing excellent drug delivery systems for cancer therapy.
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