BIOMATERIALS
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2017
·
IF 8.402
Jing Wei,Xiaoyu Shuai,Rui Wang,Xueling He,Yiwen Li,Mingming Ding,Jiehua Li,Hong Tan,Qiang Fu
Targeted delivery of therapeutics and diagnostics using nanotechnology holds great promise to minimize the side effects of conventional chemotherapy and enable specific and real-time detection of diseases. To realize this goal, we report a clickable and imageable nanovehicle assembled from multiblock polyurethanes (MPUs). The soft segments of the polymers are based on detachable poly(ethylene glycol) (PEG) and degradable poly(ε-caprolactone) (PCL), and the hard segments are constructed from lysine- and cystine-derivatives bearing reduction-responsive disulfide linkages and click-active alkynyl moieties, allowing for post-conjugation of targeting ligands via a click chemistry. It was found that the cleavage of PEG corona bearing a pH-sensitive benzoic-imine linkage (BPEG) could act as an on-off switch, which is capable of activating the clicked targeting ligands under extracellular acidic condition, followed by triggering the core degradation and payload release within tumor cells. In combination with superparamagnetic iron oxide nanoparticles (SPION) clustered within the micellar core, the MPUs exhibit excellent magnetic resonance imaging (MRI) contrast effects and T 2 relaxation in vitro , as well as magnetically guided MR imaging and multimodal targeting of therapeutics to tumor precisely, leading to significant inhibition of cancer with minimal side effect. This work provides a safe and versatile platform for the further development of smart theranostic systems for potential magnetically-targeted and imaging-guided personalized medicine.
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JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY
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2018
·Vol. 18
·期 12
·8070-8077
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IF 1.354
Zhao Hongli,Sun Shanshan,Wang Zhaodong,Hong Yayun,Shi Lulu,Lan Minbo
In this work, a novel combination of drug therapy and cryotherapy for tumor treatment was developed. Pluronic F127 modified with poly(acrylic acid) at two terminals (denoted as PAA-PF127-PAA) was used as carriers for doxorubicin (DOX) delivery. Due to the pH-sensitive property endowed
by PAA, the DOX-loaded PAA-PF127-PAA micelles released DOX faster in the slightly acidic physiological environment of the tumor site than that in the neutral physiological environment. Three-group rats bearing Walker 256 carcinosarcoma were respectively treated with cryotherapy, combination
of DOX-loaded micelles and cryotherapy, and saline injection to investigate the effect of the combined therapy. The apoptosis rate of TdT-mediated dUTP nick-end labeling (TUNEL) slices indicated that compared with cryotherapy alone, the DOX-loaded PAA-PF127-PAA micelles combining with cryotherapy
showed increased apoptosis. Thus, the combination of drug therapy and cryotherapy can be used as an effective technique for tumor treatment.
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Journal of Pharmaceutical Analysis
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2025
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IF 8.9
Runan Zuo,Linran Fu,Wanjun Pang,Lingqing Kong,Liangyun Weng,Zeyuan Sun,Ruichao Li,Shaoqi Qu,Lin Li
Antimicrobial resistance (AMR) is a growing public health crisis that requires innovative solutions. Emerging multidrug resistant (MDR) Salmonella typhimurium has raised concern for its effect on pathogenic infection and mortality in humans caused by enteric diseases. To combat these MDR Salmonella typhimurium pathogens, highly effective and broad-spectrum antibiotics such as flufenicol (FFC) need to be evaluated for their potent antibacterial activity against Salmonella typhimurium . However, the low solubility and low oral bioavailability of flufenicol need to be addressed to better combat AMR. In this work, we develop a novel nano-formulation, flufenicol nano-micelles (FTPPM), which are based on D-α-tocopherol polyethylene glycol 1000 succinate (TPGS)/poloxamer 188 (P188), for the targeted treatment of biofilms formed by drug-resistant Salmonella typhimurium in the intestine. Herein, FTPPM were prepared via a thin film hydration method. The preparation process for the mixed micelles is simple and convenient compared with other existing nanodrug delivery systems, which can further decrease production costs. The optimized FTPPM demonstrated outstanding stability and sustained release. An evaluation of the in vivo anti-drug-resistant Salmonella typhimurium efficacy demonstrated that FTPPM showed a stronger efficacy (68.17%) than did florfenicol-loaded TPGS polymer micelles (FTPM), flufenicol active pharmaceutical ingredients (FFC-API), and flufenicol commercially available medicine (FFC-CAM), and also exhibited outstanding biocompatibility. Notably, FTPPM also inhibited drug-resistant Salmonella typhimurium from forming biofilms. More importantly, FTPPM effectively restored intestinal flora disorders induced by drug-resistant Salmonella typhimurium in mice. In summary, FTPPM significantly improved the solubility and oral bioavailability of florfenicol, enhancing its efficacy against drug-resistant Salmonella typhimurium both in vitro and in vivo . FTPPM represent a promising drug-resistant Salmonella typhimurium treatment for curbing bacterial resistance via oral administration.
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JOURNAL OF NANOBIOTECHNOLOGY
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2025
·Vol. 23
·期 1
·1-24
·
IF 12.6
Yu Yang,Kong Liang,Guo Rui-bo,Zhang Ya-ni,Li Shu-tong,Zhang Feng-yuan,Wang Xin,Liu Yang,Li Xiu-Ying,Li Xue-tao
Background The imbalance of macrophage polarization plays a pivotal role in the progression of rheumatoid arthritis (RA). Reprogramming macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype is considered a promising therapeutic strategy. Methods To address this challenge, Panax notoginseng polysaccharides (PNP) with varying molecular weights were chemically conjugated with deoxycholic acid (DC) to obtain amphiphilic conjugates (PNP-DC), which self-assembled into micelles (PNP-Ms). After screening for optimal molecular weight, folic acid (FA) was introduced onto the micelle surface, and Polyphyllin I (PPI) was encapsulated to form FA-modified, PPI-loaded micelles (FA-PPI-Ms) with macrophage-targeting capability. Results FA-PPI-Ms showed enhanced cellular uptake via FA receptor–mediated endocytosis and effectively eliminated reactive oxygen species (ROS), reduced inflammatory cytokine production, and exhibited good biosafety. In vivo, FA-PPI-Ms significantly alleviated joint swelling and inflammation in RA rat models. Mechanistic studies based on RNA sequencing and experimental validation revealed that FA-PPI-Ms suppressed the JAK2/STAT3 signaling pathway, thereby promoting M2 macrophage polarization and restoring the M1/M2 balance. Conclusion This study presents a novel FA-PPI-Ms delivery system for targeted macrophages. By modulating polarization through inhibition of JAK2/STAT3 signaling, the system offers a promising therapeutic strategy for RA and potentially other inflammatory diseases.
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ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Rong Wang,Qiaoying Hu,Susu Huang,Yuelin Fang,Xinru Kong,Prabhleen Kaur,Jicheng Zhang,Yanqing Wang,Dongzhu Liu,Hang Wu,Yingying Li,Jianbo Ji,Xiaoye Yang,Lei Ye,Guangxi Zhai
Surgical resection remains the most common method of tumor treatment; however, the high recurrence and metastasis after surgery need to be solved urgently. Herein, we report an injectable zwitterionic hydrogel based on “thiol-ene” click chemistry containing doxorubicin (DOX) and a macrophage membrane (MM)-coated 1-methyl-tryptophan (1-MT)-loaded polyamide-amine dendrimer (P-DOX/1MT) for preventing the postoperative recurrence of tumors. The results indicated that P-DOX/1MT@MM exhibited enhanced recognition and uptake of the dendrimer by tumor cells and induced the immunogenic cell death. In the mice tumor model, the P-DOX/1MT@MM-Gel exhibited high therapeutic efficiency, which could significantly reduce the recurrence of the tumor, including suppressing tumor growth, promoting dendritic cell maturation, and increasing tumor-infiltrating cytotoxic T lymphocytes. The mechanism analysis revealed that the hydrogel greatly reduces the side effects to normal tissues and significantly improves its therapeutic effect. 1MT in the hydrogel is released more rapidly, improving the tumor suppressor microenvironment and increasing the tumor cell sensitivity to DOX. Then, the DOX in the P-DOX/1MT@MM effectively eliminatedo the residual tumor cells and exerted enhanced toxicity. In conclusion, this novel injectable hydrogel that combines chemotherapy and immunotherapy has the property of sequential drug release and is a promising strategy for preventing the postoperative recurrence of tumors.
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FOOD CHEMISTRY
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2025
·
IF 9.8
Siyu Zhang,Yu Ma,Xinyu Wang,Xiaoyu Zhou,Yong Fang,Wen Shen,Xuemei Ge
Shrimp are nutritious but highly perishable and initial spoilage is not easily recognized. This study developed the bifunctional film for the preservation and freshness monitoring of shrimp. Cinnamon essential oil (CEO) was loaded in PEG-PCL-micelle to improve the stability and long-time release for enhanced antimicrobial activity. Blueberry anthocyanin (BA), pH-responsive for freshness assessment, was incorporated together with CEO-Micelles in Polyvinyl alcohol (PVA) electrospunning film. BA's stability and sensitivity were improved due to the high surface area and porosity. The bifunctional film could reduce pH, total viable counts (TVC), total volatile basic nitrogen (TVB-N), and delay the spoilage of shrimp. The film color change depends on the increased pH by TVB-N during storage. The red, green, blue (RGB) changes and TVB-N values shows linear correlation(R 2 = 0.9703), indicated that bifunctional film can be used as a colorimetric indicator for monitoring shrimp deterioration. This dual-functional film offers a promising strategy for intelligent food packaging.
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Journal of Materials Chemistry B
·
2019
·Vol. 7
·期 24
·3884-3893
·
IF 5.047
Yuancheng Liu,Fan Chen,Kui Zhang,Quan Wang,Yuanwei Chen,Xianglin Luo
Conventional cross-linked micelles may suffer from low drug loading efficiency, side effects or toxicity of residual cross-linkers and complicated preparation processes of drug-loaded micelles. Herein, pH-sensitive reversibly cross-linked micelles by phenol–yne click via curcumin (Cur) were developed by combining drug loading and cross-linking using poly(ethylene glycol)-b-poly(2-methacrylate ethyl 5-hexynoicate), (mPEG-b-PHEMA-5HA), as a drug delivery system. mPEG-b-PHEMA-5HA was synthesized by ATRP of 2-hydroxyethyl methacrylate (HEMA) using mPEG-Br as a macroinitiator and then by esterification with 5-hexynoic acid. mPEG-b-PHEMA-5HA could form micelles and the micelles could load Cur. Meanwhile, the Cur loaded micelles were readily cross-linked by a phenol–yne click reaction. The cross-linked micelles showed excellent stability after high dilution with water, and turned into smaller micelles under an acid environment (pH 5.0). The cross-linked micelles achieved a higher drug loading of Cur (17.81%, wt%) than the noncross-linked micelles, due to physical entrapment and chemical click reaction. Cur release from the Cur-cross-linked micelles was inhibited under physiological conditions (pH 7.4) but was faster at pH 5.0 in comparison with the noncross-linked micelles. The cross-linked micelles exhibited a superior antitumor activity with a lower IC50 of 4.86 and 9.6 μg mL−1 toward HeLa and 4T1 cells, respectively, resulting from effective internalization by tumor cells. In pharmacokinetics, the cross-linked micelles showed a prolonged circulation time, and thus exhibited more effective inhibition of tumor growth compared to free Cur and Cur loaded noncross-linked micelles in in vivo experiments. Therefore, pH-sensitive reversibly cross-linked micelles via Cur are promising as an antitumor drug delivery system.
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RSC Advances
·
2019
·Vol. 9
·期 54
·31264-31273
·
IF 3.049
Wei Li,Cheng Tao,Jiexin Wang,Yuan Le,Jianjun Zhang
The complex construction within the oral cavity causes incomplete surgical resection of oral squamous cell carcinoma (OSCC) that may enhance the risk of recurrence and metastasis in the treatment. In situ forming injectable hydrogels with minimally invasive procedures, encapsulation stability and stimuli-responsive degradation have emerged as promising carriers for local drug delivery. In this study, doxorubicin (DOX) was first encapsulated in biodegradable poly(D,L-lactide)-poly(ethylene glycol)-poly(D,L-lactide) (PDLLA-PEG-PDLLA) micelles and then loaded into an in situ injectable hyaluronic acid (HA) hydrogel, which was cross-linked by a matrix metalloproteinase-2 (MMP-2)-responsive peptide (GCRDGPQGIWGQDRCG) through a Michael addition reaction. In vitro studies demonstrated that the HA hydrogel had a sensitive MMP-2-responsive drug release profile. Investigations including MTT, live-dead, apoptosis, and wound healing assays illustrated that DOX micelle-loaded HA hydrogels exhibited outstanding cytotoxicity against squamous carcinoma cells (SCC-15). Furthermore, by in vivo studies, we also proved that HA hydrogels degraded faster in the tumor site than in normal tissue, which led to a local sustained release of DOX-loaded micelles and tumor growth inhibition of oral squamous cell carcinoma (OSCC) without any damage to the organs. Therefore, this work provides a remarkable drug delivery platform for local chemotherapy and other applications.
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Polymer Chemistry
·
2021
·Vol. 12
·期 14
·2132-2140
·
IF 5.582
Qian Wang,Jing Xiao,Yanhong Su,Jianwen Huang,Jihua Li,Lige Qiu,Meixiao Zhan,Xu He,Weizhong Yuan,Yong Li
Amphiphilic thermoresponsive block helical poly(phenyl isocyanide) was synthesized by the polymerization of phenyl isocyanide using a Pd(II) complex catalyst as an initiator. The polymer could self-assemble into spherical micelles. The lower critical solution temperature (LCST) of the micelle solution was adjusted by changing the molar ratio of the hydrophobic segment to the hydrophilic segment and finally optimized to be 41 °C at a molar ratio of 1 : 2. After loading Fe3O4 nanoparticles, the magnetic complex micelles were prepared. The magnetic complex micelles demonstrated reversible thermoresponsiveness and obvious magnetic hyperthermia. Cell viability measurements indicated that the nanomaterials were well-biocompatible and nontoxic. The magnetic complex micelles could be used as nanocarriers to achieve controlled release of doxorubicin (DOX) by altering the temperature. Intracellular experiments demonstrated that the magnetic complex micelles showed excellent anticancer synergistic thermo-chemotherapy performance under an alternating magnetic field (AMF) owing to magnetic hyperthermia from micelle-loaded Fe3O4 nanoparticles and effective drug release due to the morphology change of thermoresponsive poly(phenyl isocyanide)s.
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JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE
·
2019
·Vol. 30
·期 8
·1-14
·
IF 2.467
Wang Jun,Li Shunying,Chen Tingting,Xian Wenjiao,Zhang Huiwu,Wu Lei,Zhu Wenting,Zeng Qingbing
To enhance the bioavailability of protein therapeutants and improve the stability of storage and delivery, a series of branched amphiphilic block copolymers consisting of cholic acid (CA) initiated poly(D,L-lactide-co-glycolide) (CA-PLGA) and water-soluble polyethyleneimine cross-linked polyethylene glycol (PEI-PEG) denoted as CA-PLGA-b-(PEI-PEG) were synthesized and characterized. CA-PLGA-b-(PEI-PEG) presented low cytotoxicity by MTT and cck-8 assay. The cationic CA-PLGA-b-(PEI-PEG) micelles (diameter about 100 nm and zeta potential 34–61 mV) were prepared through self-assembly method, and complexed with insulin via electrostatic interaction to obtain nanoscale micelle/insulin complexes. The micelle/insulin complexes-loaded CA-PLGA microspheres (MIC-MS, 10.4 ± 3.85 μm) were manufactured by employing a double emulsion (W 1 /O/W 2 ) method. The in vitro insulin release behavior and in vivo hypoglycaemic effect of MIC-MS on streptozotocin (STZ) induced diabetic rats were compared with those of the insulin-loaded CA-PLGA microspheres (INS-MS, 7.8 ± 2.57 μm). The initial burst in vitro release of MIC-MS was markedly lower than that of INS-MS ( P < 0.01), and the pharmacological availability of MIC-MS via subcutaneous administration was 148.9% relative to INS-MS. Therefore, the cationic CA-PLGA-b-(PEI-PEG) micelles can effectively increase the bioavailability of insulin in CA-PLGA microspheres and can be considered as a potential protein carrier.
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International Journal of Nanomedicine
·
2023
·
IF 8
Qiang Huo,Jianhua Zhu,Yimin Niu,Huihui Shi,Yaxiang Gong,Yang Li,Huihui Song,Yang Liu
Multidrug resistance (MDR) remains a major challenge for providing effective chemotherapy for many cancer patients. To address this issue, we report an intelligent polymer-based drug co-delivery system which could enhance and accelerate cellular uptake and reverse MDR. The nanodrug delivery systems were constructed by encapsulating disulfiram (DSF), a P-glyco-protein (P-gp) inhibitor, into the hydrophobic core of poly(ethylene glycol)-block-poly(l-lysine) (PEG-b-PLL) block copolymer micelles, as well as 2,3-dimethylmaleic anhydride (DMA) and paclitaxel (PTX) were grafted on the side chain of l-lysine simultaneously. The surface charge of the drug-loaded micelles represents as negative in plasma (pH 7.4), which is helpful to prolong the circulation time, and in a weak acid environment of tumor tissue (pH 6.5–6.8) it can be reversed to positive, which is in favor of their entering into the cancer cells. In addition, the carrier could release DSF and PTX successively inside cells. The results of in vitro studies show that, compared to the control group, the DSF and PTX co-loaded micelles with charge reversal exhibits more effective cellular uptake and significantly increased cytotoxicity of PTX to MCF-7/ADR cells which may be due to the inhibitory effect of DSF on the efflux function of P-gp. Accordingly, such a smart pH-sensitive nanosystem, in our opinion, possesses significant potential to achieve combinational drug delivery and overcome drug resistance in cancer therapy.
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Asian Journal of Pharmaceutical Sciences
·
2021
·
IF 6.598
Yong Xu,Shi Wang,Longshun Yang,Yuhang Dong,Yafang Zhang,Guoqing Yan,Rupei Tang
TPGS approved by FDA can be used as a P-gp inhibitor to effectively reverse multi-drug resistance (MDR) and as an anticancer agent for synergistic antitumor effects. However, the comparatively high critical micelle concentration (CMC), low drug loading (DL) and poor tumor target limit its further clinical application. To overcome these drawbacks, the pH-sensitive star-shaped TPGS copolymers were successfully constructed via using pentaerythritol as the initial materials, ortho esters as the pH-triggered linkages and TPGS active-ester as the terminated MDR material. The amphiphilic star-shaped TPGS copolymers could self-assemble into free and doxorubicin (DOX)-loaded micelles at neutral aqueous solutions. The micelles exhibited the lower CMC (8.2 × 10 −5 mg/ml), higher DL (10.8%) and long-term storage and circulation stability, and showed enhanced cellular uptake, apoptosis, cytotoxicity, and growth inhibition for in vitro MCF-7/ADR and/or MCF-7/ADR multicellular spheroids and in vivo MCF-7/ADR tumors via efficiently targeted drug release at tumoral intracellular pH (5.0), MDR reversal of TPGS, and synergistic effect of DOX and TPGS. Therefore, the pH-sensitive micelles self-assembled from star-shaped TPGS copolymers with ortho ester linkages are potentially useful to clinically transform for enhanced MDR cancer treatment.
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