JOURNAL OF CONTROLLED RELEASE
·
2026
·
IF 12.4
Weiqi Zhang,Linjia Chen,Yahui Dong,Yinghua Zeng,Yongyu Chen,Yue Liu,Jingru Wang,Fujun Shi
Triple-negative breast cancer (TNBC) remains a formidable clinical challenge due to the lack of druggable targets and intrinsic resistance to conventional therapies. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, represents a promising therapeutic vulnerability in TNBC. Here, we identify solute carrier family 7 member 5 (SLC7A5) as a ferroptosis-suppressing prognostic target, and develop a tumor microenvironment (TME)-responsive camptothecin (CPT)-peptide conjugates (CPCs) nanoassembly for in situ delivery of the SLC7A5 inhibitor JPH203 to TNBC. The CPCs integrate an active tumor targeting motif, a CPT-based hydrophobic core that drives self-assembly, and a gelatinase-cleavable linker for enzyme-responsive disassembly. Upon TME-triggered release, JPH203 effectively blocks leucine uptake, suppresses mTORC1 signaling, disrupts iron and redox homeostasis, and synergizes with mitochondrial reactive oxygen species to induce potent ferroptosis, achieving an 81.2% tumor growth suppression rate in orthotopic 4 T1 models with favorable biosafety. Importantly, CPCs-JPH promotes dendritic cell maturation, activates CD8 + T-cell responses, and significantly improves survival outcomes in orthotopic 4 T1 tumor-bearing mice. This work establishes a multifunctional and enzyme-responsive nanoplatform that harnesses ferroptosis to overcome therapeutic resistance while concurrently engaging innate and adaptive immunity in TNBC.
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2020
·
IF 4.845
Xia Yuan,Li Liu,Wei Wang,Ya-ru Gao,Die Zhang,Ting-ting Jia,Hai-rong Zeng,Gang Pan,Yi Yuan
The development of small molecule anticancer drugs , with low water solubility and high toxicity, into polymeric prodrugs has developed into a promising strategy in clinical application. In this study, we synthesized a novel G3-C12-mediated esterase-sensitive tumor-targeting polymeric prodrug of camptothecin (CPT), P(OEGMA- co -CPT- co -G3-C12), and explored its anticancer activity against androgen-independent prostate cancer in vitro and in vivo. Compared to free CPT, the multifunctional polymeric prodrug demonstrated improved water solubility and stability, higher intracellular uptake, and enhanced cytotoxicity in DU145 cells in vitro. Furthermore, it displayed an improved accumulation in the tumor and an enhanced anticancer activity in vivo. Hence, P(OEGMA- co -CPT- co -G3-C12) could be a promising drug in the treatment of androgen-independent prostate cancer.
研究领域:
肿瘤学
·
药学
·
癌症治疗
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DOI
PubMed
高影响因子
Analytical Methods
·
2015
·Vol. 7
·期 19
·8100-8108
·
IF 1.821
Haochi Liu,Yansuo Hong,Ligang Chen
A molecularly imprinted polymer (MIP)-matrix solid phase dispersion (MSPD) method for the extraction of camptothecin from Camptotheca acuminate was developed. MIPs were synthesized by a surface imprinting technique using carbon nanotubes as a support, camptothecin as a template, methacrylic acid as a functional monomer, and ethylene glycol dimethacrylate as a crosslinker. The MIPs were characterized by scanning electron microscopy, transmission electron microscopy and Fourier transform-infrared spectroscopy. Isothermal adsorption, dynamic adsorption and selectivity adsorption experiments were also carried out in this study. The MIP-MSPD method coupled with high performance liquid chromatography was applied for the determination of camptothecin in Camptotheca acuminate fruit, bark and leaf. Factors affecting the extraction yield such as the sorbent/sample ratio, dispersion time, and washing and elution solvents were investigated. Under optimized conditions, a good linearity of camptothecin was obtained in a range of 1–200 μg mL−1, and the detection limit of the method was 0.13 μg mL−1. The extraction yields of camptothecin obtained were 0.1055%, 0.0628% and 0.0930% for Camptotheca acuminate fruit, bark and leaf, respectively. The recovery of camptothecin was in the range of 96.1–103.3%. The results showed that this method is fast, selective, cost-effective and environmentally friendly compared with other extraction methods such as stirring extraction, ultrasonic extraction and Soxhlet extraction used for the extraction of camptothecin.
研究领域:
植物化学
·
分析化学
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高影响因子
CHEMICAL RESEARCH IN CHINESE UNIVERSITIES
·
2016
·Vol. 32
·期 4
·630-633
·
IF 1.086
Zhu Jian,Jin Zhimin
After being hydrolyzed into corresponding hydrosoluble carboxylate by 1,1,3,3,-tetramethylguanidine (TMG), camptothecin was extracted via the aqueous two-phase systems composed of ionic liquid 1,1,3,3-tetramethylguanidinium(TMGM) carboxylate and K 2 CO 3 , and was regenerated at the final by dilute aqueous hydrochloric acid. Among the ionic liquids, TMGM benzoate showed the best effect, TMGM formate the worst, this results were consistent with the liposolubilities of different carboxylic acid components in the ionic liquids. Through two-step extraction of TMGM benzoate ionic liquid/K 2 CO 3 aqueous two-phase at a favorable condition, camptothecin was obtained in a purity of 98.3% and a total yield of 85.1%, from the crude camptothecin extract with a purity of 14.2%.
研究领域:
药学
·
分离科学
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DOI
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Li Xiang,Xin Wang,Yaru Shao,Qiangqiang Jiao,Jiang Cheng,Xiaotong Zheng,Shaobing Zhou,Yuping Chen
As the central cellular player in fibrogenesis, activated hepatic stellate cells (aHSCs) are the major target of antifibrotic nanomedicines. Based on our finding that activated HSCs increase the expression of folate receptor alpha (FRα), we tried to apply folic acid (FA) decoration to generate an active drug-targeting at aHSCs and suppress hepato-fibrogenesis. FA-conjugated poly(ethylene glycol)-poly(ε-caprolactone) copolymers (PEG-PCL) were synthesized and self-assembled into the spherical micelles that owned a uniform size distribution averaging at 60 nm, excellent hemo- and cyto-compatibility, and pH-sensitive stability. These FA-modified micelles were preferentially ingested by aHSCs as expected and accumulated more in acutely CCl4 injured mouse livers compared to nondecorated counterparts. Such an aHSC targetability facilitated the loaded medicinal camptothecin (CPT) to achieve a greater therapeutic efficacy and inhibition of MF phenotypic genes in aHSCs. Encouragingly, though free CPT and nontargeting CPT micelles produced negligible curative outcomes, FA-decorated CPT micelles yielded effectively remedial effects in chronically CCl4-induced fibrotic mice, as represented by a significant shrinkage of aHSC population, suppression of fibrogenesis, and recovery of liver structure and function, clearly indicating the success of the folate decoration-supported aHSC-targeted strategy for antifibrotic nanomedicines in fibrosis resolution.
研究领域:
药学
·
肝病学
·
纳米医学
·
药物递送系统
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PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE
·
2025
·Vol. 36
·期 1
·1-17
·
IF 4.5
Wang Zheng,Ye Minhua,Wang Chunguo,Ma Dehua,Zhang Jian,Fang Fang
This study aimed to develop a versatile aptamer-conjugated, photothermal responsive camptothecin (CPT)-loaded chitosan-bimetallic (Pd/Au) nanoparticles (Ap-CH-CPT-Pd/Au NPs) to enhance cytotoxicity in lung cancerous NCI-H446 and H1299 cells. The CH-CPT-Pd/Au NPs exhibited polydispersity with a diameter of 33.87 ± 2.23 nm. FTIR investigation revealed the presence of chitosan and camptothecin in chitosan-camptothecin-palladium/gold nanoparticles. The 2θ of CH-CPT-Pd/Au corresponded to chitosan and palladium/gold. The Ap-CH-CPT-Pd/Au NPs (180 μg/mL) subjected to near-infrared (NIR) treatment elevated the temperature to over 50 °C. The optimum CPT concentration was 0.075% in CH-CPT-Pd/Au, demonstrating a hydrodynamic diameter of 113.12 ± 16.78 nm, a drug loading efficiency (DLE) of 10.89 ± 0.53%, and a drug encapsulation efficiency (DEE) of 63.97 ± 4.21%. A CPT release rate of 7.23 ± 3.25% was recorded at pH = 5.4 after 74 h. In addition, NIR+Ap-CH-CPT-Pd/Au NPs exhibited negligible toxicity to red blood cells (RBCs). However, enhanced cytotoxicity in NCI-H446 and H1299 lung carcinoma cells is achieved through the induction of oxidative stress-mediated apoptosis.
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高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2012
·
IF 3.456
Qian Guo,Ping Luo,Yu Luo,Fang Du,Wei Lu,Shiyuan Liu,Jin Huang,Jiahui Yu
Biodegradable micelles with sheddable poly(ethylene glycol) shells were fabricated based on poly(ethylene glycol)- block -poly(γ-benzyl l -glutamate) (mPEG-SS-PBLG) diblock copolymer and applied as the carrier of 7-ethyl-10-hydroxy-camptothecin (SN-38) in order to enhance its solubility and stability in aqueous media. The diblock polymer was designed to have the hydrophilic PEG moiety and hydrophobic PBLG moiety linked by biodegradable disulfide bond, so in reducing environment the PEG shells can be detached. The polymer was able to form the micelles of nano-scale in aqueous media, suggesting their passive targeting potential to tumor tissue. Water-insoluble antitumor drug, SN-38, was easily encapsulated into mPEG-SS-PBLG nanomicelles by lyophilization method. When setting theoretical drug loading content at 10 wt%, the drug encapsulation efficiency (EE) was assayed as 73.5%. Owing to the disulfide bond in mPEG-SS-PBLG, intense release of SN-38 occurred in the presence of dithiothreitol (DTT) at the concentration of simulating the intracellular condition, however, micelles showed gradual release of SN-38 in the absence of DTT. Also, the mPEG-SS-PBLG micelles effectively protected the active lactone ring of SN-38 from hydrolysis under physiological condition. Compared with free SN-38, SN-38-loaded nanomicelles showed essentially decreased cytotoxicity against L929 cell line in 24 h, bare mPEG-SS-PBLG nanomicelles showed almost non-toxicity.
研究领域:
药学
·
生物医学工程
·
肿瘤学
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DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2017
·
IF 4.164
Can Wu,Ruixin Li,Yajun Yin,Junling Wang,Li Zhang,Wenying Zhong
A redox-responsive supramolecular hydrogel system was developed for delivering 10-hydroxy camptothecin (HCPT). The hydrogel was formed by cleaving disulfide bond. The combination of hydrophobic HCPT with hydrogel was a simple and effective way to improve the solubility of HCPT and the drug loading capacity of delivery system. The transmission electron microscopy (TEM) image revealed the self-assembled hydrogel was long and thin nanofibers with a width of < 10 nm. Rheological test verified the hydrogel had fine physical properties. In vitro release experiment showed that the accumulative releasing percentages within 72 h of HCPT-peptide hydrogels at 3.0%, 4.0%, 5.0% were 16.8%, 21.3%, and 26.8% respectively, which indicated the HCPT-peptide hydrogels had a significantly sustained-release characteristic. Besides, in vitro anticancer assay showed that HCPT-peptide hydrogels possessed a favorable anticancer efficacy. These results indicated that HCPT-peptide hydrogel had great potential for cancer treatment as a novel injectable drug delivery system.
研究领域:
药学
·
生物材料
·
肿瘤学
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DOI
高影响因子
CHEMISTRY & BIODIVERSITY
·
2024
·
IF 2.3
Kalpana Sukumar,Muruganantham Bharathi,Abdurahman Hajinur Hirad,Abdullah A. Alarfaj,Samer Hasan Hussein-Al-Ali,Surya Parthasarathy
Innovative drug delivery platforms for selective, regulated, and sustained release of anticancer drugs are crucial in cancer treatment. This study presents nanoparticles developed from chitosan (CS), graphene oxide (GO), and magnetite (Fe3O4), and their nanocomposites, to enhance the loading and release efficiency of camptothecin (CPT). Nanostructures were characterized using imaging microscopy, FT-IR, and X-ray diffraction, with an average crystallite size of 5.5 nm. Camptothecin binding proportions were 70% for CS, 81% for CS@Fe3O4, 58% for CS@GO, and 74% for CS@GO/Fe3O4. At pH 5.0, CPT release ratios were 87%, 80%, 88%, and 90%, respectively, and at pH 7.4, 84%, 72%, 89%, and 87%. Cytotoxicity was assessed using the MTT assay against HepG2 and SMMC-7721 cancer cells. CPT-CS@GO/Fe3O4 exhibited the highest survival at 5 µM and 12.5 µM concentrations, indicating it as the most effective nanocarrier for camptothecin delivery. The study demonstrates CS@GO/Fe3O4's potential as a superior drug delivery system.
研究领域:
纳米技术
·
药学
·
癌症研究
·
材料科学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2021
·
IF 5.875
Congjun Xu,Haolan Yang,Zhanghong Xiao,Tao Zhang,Zilin Guan,Jie Chen,Hualu Lai,Xiaoyu Xu,Yanjuan Huang,Zeqian Huang,Chunshun Zhao
The pentose phosphate pathway (PPP) plays a critical role by providing ribulose-5-phosphate (Ru5P) and NADPH for nucleotide synthesis and reduction energy, respectively. Accordingly, blocking the PPP process may be an effective strategy for enhancing oxidation therapy and inhibiting cell replication. Here, we designed a novel reduction-responsive PEGylated prodrug and constructed nanoparticles [email protected] to simultaneously deliver a PPP blocker, dehydroepiandrosterone (DHEA), and chemotherapeutic camptothecin (CPT) to integrate amplification of oxidation therapy and enhance cell replication inhibition. Following cellular uptake, DHEA and CPT were released from [email protected] in the presence of high glutathione (GSH) levels. As expected, DHEA-mediated reduction level decreases and CPT-induced oxidation level increases synergistically, breaking the redox balance to aggravate cancer oxidative stress. In addition, suppressing nucleotide synthesis by DHEA through the reduction of Ru5P and blocking DNA replication by CPT further motivates a synergistic inhibition effect on tumor cell proliferation . The results showed that [email protected] featuring multimodal treatment has satisfactory antitumor activity both in vitro and in vivo . This study provides a new tumor treatment strategy, which combines the amplification of oxidative stress and enhancement of inhibition of cell proliferation based on inhibition of the PPP process.
研究领域:
药理学
·
肿瘤学
·
纳米技术
·
生物化学
·
治疗学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2020
·
IF 3.616
Wei He,Yawei Du,Wenya Zhou,Tao Wang,Man Li,Xinsong Li
As an important DNA topoisomerase I inhibitor in oncotherapy, camptothecin (CPT) with traditional formulation only shows a limited clinical application mainly because of its poor solubility. In this study, a novel redox responsive nanoscaled delivery system was developed to overcome the inherent defect of CPT. Firstly, a CPT prodrug (CPT-LA) and two crosslinkable surfactants (SO-LA and MPEG-LA) was synthesized, all of which contained the same lipoic acid (LA) structure. In the preparation, highly core-crosslinked structure was formed by adding a thiol crosslinker, which can induce LA ring opening polymerization and disulfide crosslinking. The resulting CPT-LA core-crosslinked nanomicelles (CPT-LA CNM) were formulated with a highly crosslinked core and a PEG hydrophilic shell. Dynamic light scattering (DLS) characterization indicated that CPT-LA CNM possessed a narrow size distribution (184.6 ± 3.6 nm) and negatively charged zeta potential (−3.5 ± 1.2 mV). The storage and physiological stabilities showed that the size distribution of CPT-LA CNM was relatively stable in both conditions which were neutral PBS at 4 °C (1 week period) and PBS containing 10% serum at 37 °C (24 h period). Moreover, the effective CPT release behavior of CPT-LA CNM was confirmed in the reducing circumstances containing dithiothreitol (DTT). Under confocal laser scanning microscopy (CLSM), CPT-LA CNM demonstrated a rapid cellular uptake behavior against cancer cells when compared to CPT suspension. Finally, the enhanced anticancer efficacy of CPT-LA CNM was also detected by in vitro cytotoxicity and cell apoptosis assay . In summary, the core-crosslinked CPT-LA CNM could be a promising CPT delivery system because of high stability, effectively controlled release as well as improved anticancer activity.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
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PubMed
高影响因子
Polymer Chemistry
·
2015
·Vol. 6
·期 12
·2192-2203
·
IF 5.52
Yun Zhang,Maohua Chen,Xiaoming Luo,Hong Zhang,Chaoyu Liu,Huiyan Li,Xiaohong Li
Micelle behaviors have been studied intensively for linear block copolymers, and amphiphilic polymers with a non-linear architecture, including star polymers, dendrimers, and hyperbranched polymers are showing advantages in the loading of anticancer drugs. In the current study, multiarmed amphiphilic copolymers with drug conjugates were developed for the construction of micelles to alleviate premature drug release during circulation and to achieve glutathione (GSH)-mediated intracellular drug delivery. Folic acid (FA) was grafted on some of the arms of 4-armed poly(ethylene glycol) (4-arm-PEG) as the targeting groups of micelles, and ε-caprolactone (ε-CL) was copolymerized with PEG from the rest of the arms, followed by camptothecin (CPT) conjugation through dithiodipropionic acid. The effect of the number of arms used for FA conjugation and the length of PCL blocks on micelle properties, reductive sensitivity, cellular uptake, and antitumor activities were evaluated. The amphiphilic copolymers with star-shaped miktoarms were self-assembled into micelles with an average size of around 100 nm and critical micelle concentrations (CMCs) as low as 0.8 μg mL−1. The distribution of hydrophobic PCL segments in more arms resulted in micelles with lower CMCs, higher structural stability, and greater sensitivity of CPT release in the presence of GSH. But, the conjugation of FA on fewer arms led to lower FA densities and less efficient cellular uptake of the micelles. In view of the performance of cellular uptake, CPT loading, and reduction-sensitive release, micelles from 4-armed copolymers with FA conjugation on two arms and PCL copolymerization on another two arms resulted in the most significant antitumor activities. It is suggested that the composition and arm structure of amphiphilic copolymers with star-shaped miktoarms show significant effects on micelle behavior, and optimal antitumor activities can be achieved through judicious selection of multiple arms for conjugating targeting groups and chemotherapeutic drugs.
研究领域:
药学
·
聚合物化学
·
癌症研究
·
药物递送系统
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）