COLLOIDS AND SURFACES B-BIOINTERFACES
·
2018
·
IF 3.997
Conglian Yang,Yuting Qin,Kun Tu,Chenfeng Xu,Zhen Li,Zhiping Zhang
Multidrug resistance (MDR) remains as an obstacle for effective cancer treatment. Herein, we developed a novel and efficient nanomedicine by virtue of the carrier characters and MDR inhibition effects of β-cyclodextrin (β-CD) and d-α-tocopheryl polyethylene glycol succinate (TPGS). A series of star-shaped polymers CD-g-TPGS with different TPGS substitution degree were synthesized for doxorubicin (DOX) delivery, where β-CD was identified as a core and TPGS as branches. These star polymers can self-assemble into nanoparticles with DOX . These nanoparticles showed no significant differences in size, zeta potential and morphology except for in vitro stability. They demonstrated good biocompatibility and enhanced cellular uptake in both drug sensitive and resistant cancer cells. Notably, the nanoparticles exhibited superiority of cytotoxicity in drug resistant cancer cells against free DOX . In vivo antitumor effect also demonstrated the improved cancer inhibition effect. This work suggests that star-shaped polymers CD-g-TPGS are promising drug carriers to overcome MDR in cancer treatment.
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高影响因子
ACS Applied Nano Materials
·
2025
·
IF 5.5
Lin Li,Tiantian Lei,Kejing Wang,Yong Liu,Bingjun Sun,Lin Chen
Chemotherapy has been established as a standard therapeutic regimen for triple-negative breast cancer (TNBC). However, the efficacy of current therapeutic approaches remains suboptimal, primarily attributed to insufficient drug accumulation and the rapid development of chemoresistance. Thus, the rational design of drug delivery systems capable of triggering multimodal cell death pathways represents a promising strategy to combat TNBC. Ferroptosis emerges as a potent form of nonapoptotic cell death, showing great potential for tumor inhibition. The effective codelivery of chemotherapeutic drugs and ferroptosis activators provides potential ideas for the treatment of TNBC. Prodrug-based nanoassemblies have attracted tremendous attention in drug delivery, especially homodimeric prodrugs with ultrahigh drug loading. However, due to their symmetric structures, most homodimeric prodrugs exhibit poor self-assembly ability. Herein, two doxorubicin (DOX) homodimeric prodrugs were designed and coassembled with a GPX4 inhibitor (ML210). The incorporation of ML210 significantly promotes the stability of DOX nanoassemblies and improves the intracellular breakage of the DOX prodrug by regulating the GSH level. As a result, the ML210-driven doxorubicin homodimeric prodrug nanoassemblies exhibit high drug loading capacity, high self-assembly stability, and synergistic chemotherapy-ferroptosis effects. Our results present a viable approach to promote the self-assembly of homodimeric prodrugs while offering an efficient nanoplatform for TNBC treatment.
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高影响因子
INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
·
2019
·
IF 3.375
Xianjing Zhou,Feng Chen,Haipeng Lu,Lingli Kong,Siyu Zhang,Wei Zhang,Jingjing Nie,Binyang Du,Xinping Wang
In this study, we designed and synthesized hybrid microgels with a positively charged cross-linking network and embedded gold nanoparticles. The hybrid microgels presented reversible thermosensitive behavior and the volume transition temperature of ∼37 °C, which was close to body temperature. These microgels were successfully applied as vectors to simultaneously deliver hydrophobic anticancer drug, doxorubicin, and anionic anti-inflammatory drug, diclofenac sodium. In the tumor microenvironment of low pH, high temperature, reduction condition, and the presence of ions, both drugs could controllably release from the microgels. Such microgels might be a promising platform for further development as an effective strategy for combination therapy.
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高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2022
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IF 5.062
Junxu Hao,Jinglei Wang,Hao Pan,Yuli Sang,Dazhuang Wang,Zeyu Wang,Jiao Ai,Bin Lin,Lijiang Chen
In this study, the ideal polymer materials were selected by molecular dynamics (MD) and dissipative particle dynamics (DPD) simulation methods, and pH and redox-sensitive micelles were prepared according to the simulation results. Through experiments, we successfully prepared hydrophilic block polyethylene glycol monomethyl ether (mPEG) connected hydrophobic block polylactic acid-glycolic acid (PLGA) amphiphilic polymer, and connected with redox fragment containing disulfide bond , and then connected with amide bond doxorubicin (DOX) to form mPEG-PLGA-SS-DOX prodrug , and further physical embedded free DOX. Finally, we obtained a particle size of 47.04 ± 0.103 nm, the potential of −23.8 ± 0.189 mV, Polymer dispersity index (PDI) of 0.231 ± 0.001, transmission electron microscopy (TEM) showed that it was spherical mPEG-PLGA-SS-DOX/DOX nanoparticles , its entrapment efficiency (EE) was 68.2%, loading content was 16.72%. The cumulative release of mPEG-PLGA-SS-DOX/DOX was 87.39% in a pH 5.0 and 10 mM Glutathione (GSH) tumor simulation environment. It was less toxic to normal cell HEK293 and more cytotoxic to HepG2 tumor cells. It showed that it was an excellent anti-tumor nano-drug. In addition, the application of computer simulation in the design of nanomedicine also provided a new research idea for the research of nanomedicine .
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高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2017
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IF 4.164
Beibei Hou,Weitao Yang,Chunhong Dong,Bin Zheng,Ying Zhang,Jing Wu,Hanjie Wang,Jin Chang
How to encapsulate and transport the payload of multiple therapeutic compounds avoiding premature leakage, and simultaneously co-release them rapidly at specific lesions still remains the major concern in clinic. Herein, we designed the UCN@mSiO 2 -(Azo + RB) (azobenzene groups and Rose Bengal) nanoimpellers, which used the multicolor-emission capability of the core-shell upconverting nanoparticles (UCNs) at a single excitation wavelength to co-release anticarcinogen doxorubicin (Dox) and reactive oxygen species (ROS) for combined chemotherapy and photodynamic therapy (PDT). The nanoimpeller was formed from UCN inner core, mesoporous silica shell, and light triggers Azo and RB molecules. The UCNs emitting UV/blue and green/red multiband light were used to activate the photoresponsive Azo and photosensitizer RB molecules; The mesoporous silica shell offered the possibilities to load anticancer drug and conjugate the light triggers; As there are strong charge interaction and hydrogen bonds between Dox and surface silanols of mesoporous silica, the azobenzene molecules worked as “gatekeeper” and “molecular stirrer” to precisely trap and propel the release of Dox under the external stimuli. The time-dependent drug release analysis, ROS production test and PDT test suggested that the nanoparticles may serve as a useful multifunctional nanoplatform for synergistic therapy and cancer diagnostic.
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DOI
PubMed
高影响因子
Pharmaceutics
·
2025
·Vol. 17
·期 12
·1574
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IF 5.5
Jeong Min Lee,Chung-Sung Lee,Chae Yeong Lee,Min Lee,Hee Sook Hwang
Background: Breast cancer remains one of the most prevalent and lethal malignancies worldwide. Although doxorubicin (DOX) is widely used as a first-line chemotherapeutic agent, its clinical utility is constrained by dose-limiting cardiotoxicity and systemic adverse effects. Nanoparticulate drug delivery systems have therefore attracted attention for improving DOX stability, biocompatibility, and tumor selectivity. In this study, we explored sterosomes—simple non-phospholipid nanocarriers composed of cholesterol and palmitic acid—as an alternative DOX delivery platform with pH-responsive properties.Methods: DOX-loaded sterosomes (DOX-STs) were prepared using cholesterol and palmitic acid to impart acid-sensitive behavior. The nanocarriers were systematically evaluated through particle characterization, physicochemical stability assessment, in vitro pH-dependent drug release, and cellular uptake studies. Furthermore, therapeutic efficacy and systemic safety were investigated in an MDA-MB-231 breast cancer xenograft mouse model.Results: DOX-STs exhibited particle sizes below 100 nm, high encapsulation efficiency, and excellent colloidal stability for 28 days. The sterosomes demonstrated accelerated DOX release under acidic conditions relative to physiological pH, consistent with their pH-responsive design. Enhanced cellular uptake was observed in both MCF-7 and MDA-MB-231 cells. In vivo, DOX-ST treatment resulted in significant tumor growth suppression and prolonged survival without notable body weight loss, indicating reduced systemic toxicity compared to free DOX.Conclusions: This study presents a simple sterosome-based nanocarrier system that achieves pH-responsive DOX release and enhanced antitumor efficacy while minimizing toxicity. These findings highlight the potential of sterosomes as a translatable nanomedicine platform for breast cancer therapy.
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高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2022
·
IF 6.1
Hang Zhang,Shaopan Bian,Zhihao Xu,Ming Gao,Han Wang,Junwei Zhang,Mingkun Zhang,Yu Ke,Weijia Wang,Zhe-Sheng Chen,Haiwei Xu
Encequidar, a gut-specific P-glycoprotein (P-gp) inhibitor, makes oral paclitaxel possible, and has been used in clinical treatment of metastatic breast cancer , however, its pharmacological effect and mechanism of reversal of drug resistance in drug-resistant colon cancer cells SW620/AD300 are still unknown. Herein, we first synthesized encequidar and demonstrated that it could inhibit the transport activity of P-gp, reduced doxorubicin (DOX) efflux, enhanced DOX cytotoxicity and promoted tumor-apoptosis in SW620/AD300 cells. Metabolomic analysis of cell samples was performed using liquid chromatography Q-Exactive mass spectrometer, the results of metabolite enrichment analysis and pathway analysis showed that the combination of encequidar and DOX could: i ) significantly affect the citric acid cycle (TCA cycle) and reduce the energy supply required for P-gp to exert its transport activity; ii ) affect the metabolism of glutathione , which is the main component of the anti-oxidative stress system, and reduce the ability of cells to resist oxidative stress; iii ) increase the intracellular reactive oxygen species (ROS) production and enhance ROS-induced cell damage and lipid peroxidation, which in turn restore the sensitivity of drug-resistant cells to DOX. In conclusion, these results provide sufficient data support for the therapeutical application of the P-gp inhibitor encequidar to reverse MDR , and are of great significance to further understand the therapeutic advantages of encequidar in anti-tumor therapy and guide clinical rational drug use.
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高影响因子
NANOTECHNOLOGY
·
2017
·Vol. 28
·期 37
·375101
·
IF 3.44
Yuwei Hu,Jian Chen,Xiufang Li,Yanhua Sun,Shen Huang,Yuqing Li,Hui Liu,Jiangfeng Xu,Shian Zhong
The current state of cancer therapy encourages researchers to develop novel efficient nanocarriers. Halloysite nanotubes (HNTs) are good nanocarrier candidates due to their unique nanoscale (40–80 nm in diamter and 200–500 nm in length) and hollow lumen, as well as good biocompatibility and low cost. In our study, we prepared a type of folate-mediated targeting and redox-triggered anticancer drug delivery system, so that Doxorubicin (DOX) can be specifically transported to tumor sites due to the over-expressed folate-receptors on the surface of cancer cells. Furthermore, it can then be released by the reductive agent glutathione (GSH) in cancer cells where the content of GSH is nearly 103-fold higher than in the extracellular matrix. A series of methods have demonstrated that per-thiol-β-cyclodextrin (β-CD-(SH)7) was successfully combined with HNTs via a redox-responsive disulfide bond, and folic acid-polyethylene glycol-adamantane (FA-PEG-Ad) was immobilized on the HNTs through the strong complexation between β-CD/Ad. In vitro studies indicated that the release rate of DOX raised sharply in dithiothreitol (DTT) reducing environment and the amount of released DOX reached 70% in 10 mM DTT within the first 10 h, while only 40% of DOX was released in phosphate buffer solution (PBS) even after 79 h. Furthermore, the targeted HNTs could be specifically endocytosed by over-expressed folate-receptor cancer cells and significantly accelerate the apoptosis of cancer cells compared to non-targeted HNTs. In vivo studies further verified that the targeted HNTs had the best therapeutic efficacy and no obvious side effects for tumor-bearing nude mice, while free DOX showed damaging effects on normal tissues. In summary, this novel nanocarrier system shows excellent potential for targeted delivery and controlled release of anticancer drugs and provides a potential platform for tumor therapy.
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PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2020
·
IF 7.182
Tingsheng Yan,Siyuan Zhu,Wenxue Hui,Jinmei He,Zhonghua Liu,Jinju Cheng
The co-delivery of chemotherapeutic drugs and siRNA has gained increasing attentions owing to the enhanced antitumor efficacy over single administration. In this work, a chitosan-based pH-responsive prodrug vector was developed for the co-delivery of doxorubicin (DOX) and Bcl-2 siRNA. The accumulation of fabricated nanoparticles in hepatoma cells was enhanced by glycyrrhetinic acid receptor-mediated endocytosis. The cumulative release amount of the encapsulated DOX and siRNA reached 90.2 % and 81.3 % in 10 h, respectively. More strikingly, this nanoplatform can efficiently integrate gene- and chemo-therapies with a dramatically enhanced tumor inhibitory rate (88.0 %) in vivo. This co-delivery system may provide the latest strategy to meet the needs of combination therapies for tumors, offering safe and efficient improvements to the synergistic antitumor efficacy of gene-chemotherapies.
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PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2025
·
IF 3.6
Lijun Wang,Miao Lei,Jie Hao,Xiaojun Zhang,Wei Jiang,Zhenming Hu
The therapeutic efficacy of chemotherapy in solid tumors such as osteosarcoma is hindered by the dense, collagen-rich extracellular matrix (ECM). In this work, we report an acid-responsive nanogel that co-encapsulates bromelain (BL), a proteolytic enzyme, and doxorubicin (DOX) with spatially distinct localization and independent pH-responsive release mechanisms. BL is encapsulated within the nanogel network, whereas DOX is covalently grafted onto the nanogel surface via an acid-labile linker, enabling the nanocarrier (ng(BL–DOX)) to remain stable under physiological conditions while promoting controlled release in the mildly acidic tumor microenvironment. The released BL degrades collagenous ECM components and reduces matrix density, thereby improving the penetration and intratumoral distribution of the concurrently released DOX. In a murine osteosarcoma model, the PEG-rich nanogels showed prolonged circulation and increased tumor accumulation via the enhanced permeability and retention (EPR) effect, accompanied by collagen I degradation and effective tumor growth inhibition, with final tumor volumes reduced to approximately one-tenth of those in the control group and without observable systemic toxicity. This microencapsulation approach provides an enzyme–drug co- encapsulation system that combines ECM degradation with chemotherapy in a single nanogel platform and may be adapted to other proteolytic enzymes and cytotoxic agents for the treatment of stroma-rich solid tumors.
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高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2025
·
IF 5.2
Kaixin Feng,Zhongkun Zhang,Jingjing Zhang,Xiaohan Xia,Siyu Yao,Yufei Wang,Min Wu
Doxorubicin (DOX) is limited by its clinical toxicity as a breast cancer therapy. Traditional liposomal formulations improve the tumor delivery of DOX but suffer from inadequate controlled release and low encapsulation efficiency of DOX. To address these, we developed a photo-responsive liposomal formulation DTTPL by co-encapsulating DOX and TiO 2 nanostructures (TiO 2 ) within D-α-tocopheryl succinate (α-TOS)-PEG liposomes. DTTPL successfully facilitated the release of DOX through the light-sensitive catalysis mechanism of TiO 2 , exhibiting 4.6 times greater cytotoxicity against MCF-7 cells compared to free DOX. Transcriptional analysis revealed synergistic DOX/DTTPL dysregulation of key genes (Brca1, Bcl-2, Bax, Caspase-3), aligning with cytotoxicity. Eventually, light-triggered DOX/DTTPL formulation resulted in 70.09% of tumor growth inhibition (TGI) in mice with no significant organ toxicity. This photo-responsive nanoformulation enables efficient controlled release of DOX, offering an alternative strategy for small molecule delivery to treat triple negative breast cancer.
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高影响因子
BIOCONJUGATE CHEMISTRY
·
2014
·
IF 4.821
Jinwen Li,Yanxia Zhou,Chengwei Li,Dishi Wang,Yajie Gao,Chao Zhang,Lei Zhao,Yushu Li,Yan Liu,Xinru Li
Dual endosomal pH-sensitive micelles were designed and fabricated to deliver doxorubicin (DOX) for treating breast cancer based on a poly(2-ethyl-2-oxazoline) (PEOz)–DOX (PEOz–hyd–DOX) conjugate. PEOz–hyd–DOX was successfully synthesized by connecting DOX to PEOz via an acid cleavable hydrazone linker and self-assembled into nanosized micelles, which further physically encapsulated DOX. The conjugate and DOX-loaded conjugate micelles displayed faster release of DOX at pH 5.0 than at pH 7.4. This pH-dependent release behavior might assist the quick diffusion of DOX from acidic endosomes or lysosomes and the intracellular transfer into the nucleus after internalization, which was confirmed by confocal laser scanning microscopy images. As expected, PEOz–hyd–DOX conjugate and DOX-loaded conjugate micelles maintained cytotoxicity of DOX. In addition, the dual endosomal pH-sensitive micelles were found to substantially enhance antitumor efficacy and reduce side effects compared with free DOX. Therefore, PEOz–hyd–DOX conjugate-based micelles might be potential drug delivery vehicles of DOX for safe and effective breast cancer therapy.
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高影响因子
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