Biomaterials Science
·
2017
·Vol. 5
·期 12
·2501-2510
·
IF 4.21
Zhaopei Guo,Xingzhi Zhou,Mengze Xu,Huayu Tian,Xuesi Chen,Meiwan Chen
Camptothecin (CPT) is a broad spectrum anticancer drug, but its application is limited due to the poor water solubility, lactone ring instability, and low drug loading potential. In this study, biocompatible cationic polypeptide-based micelles were developed to deliver dimeric CPT (DCPT) with the aim of overcoming the above-mentioned obstacles and achieving favorable therapeutic effects. Cationic polypeptide poly-lysine-block-poly-leucine (PLys-b-PLeu) was fabricated via the ring-opening polymerization of N-ε-carbobenzoxy-L-lysine (ε-Lys(Z)) and L-leucine (Leu) and further grafted with polyethylene glycol (PEG) and an arginine-glycine-aspartic acid (RGD) peptide. DCPT was synthesized by reacting CPT and 2-hydroxyethyl disulfide, and micelles were prepared using a dialysis method. The obtained DCPT-loaded RGD-PEG-g-poly-L-lysine-b-poly-L-leucine (DRPPP) micelles showed a high encapsulation efficiency of 89.7% and a high drug loading capacity of 46.1%. In addition, the DRPPP micelles remained stable under physiological conditions (PBS at a pH of 7.4) but showed rapid release when triggered by a reductive environment (PBS at a pH of 7.4 with 10 mM dithiothreitol). Compared to micelles without RGD decoration, the DRPPP micelles exhibited an increased cellular uptake through RGD targeting and were internalized into cells via caveolae-mediated endocytosis and macropinocytosis. Furthermore, the DRPPP micelles exerted an enhanced cytotoxicity against MDA-MB-231 cells compared to MCF-7 cells, which expressed less αvβ3 receptors. Besides, the DRPPP micelles induced cell apoptosis and caused a decrease of mitochondrial membrane potential. These results indicate that dimeric camptothecin-loaded cationic polypeptide-based micelle is a promising strategy for cancer therapy.
研究领域:
药学
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纳米技术
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癌症治疗
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药物递送系统
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2022
·
IF 7.033
Mingliang Su,Yukun Chen,Lijun Jia,Zhanxia Zhang
Introduction Camptothecin (CPT) is a cytotoxic quinolone alkaloid (isolated from a traditional Chinese medicine Camptotheca acuminata), used for the treatment of various malignancies, which inhibits DNA topoisomerase I (Topo I). However, its drawbacks, such as poor water solubility, stability, and highly toxic side effects, limit its clinical application. Therefore, CPT needs to be prepared as a nanomedicine to improve solubility, reduce side effects, and synergize with other therapies to improve efficacy. Methods In this work, we constructed CPT NPs (nanoparticles), which were CPT-loaded and manganese dioxide (MnO 2 )-coated polydopamine (PDA) nanomedicine. In vitro, we explored the antitumor effect including CPT NPs-induced cell proliferation inhibition, apoptosis and ferroptosis for tumor cell lines. In vivo, we established LLC tumor-bearing mice model to evaluate their tumor imaging and anticancer effects. Results CPT NPs improve the water solubility and stability of CPT and reduce its toxic effects. It has good biocompatibility, excellent photothermal conversion ability for photothermal therapy (PTT) and pH release in the tumor microenvironment. It can inhibit tumor cell proliferation, induce apoptosis and result in ferroptosis of tumor cells. More significantly, this nanomedicine can provide information for the location and diagnosis of tumors via magnetic resonance imaging. In general, the nanomedicine integrated with diagnosis and treatment has excellent anticancer effect. Discussion Altogether, this nanomedicine possesses the ability to diagnose and therapy through magnetic resonance imaging and chemo-photothermal therapy, respectively. In addition, the integrated diagnosis and treatment nanomedicine has potential clinical application prospects through treating lung cancer with high efficiency and low side effect. It can support the construction of related nano-delivery systems.
研究领域:
纳米技术
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癌症研究
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药学
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生物医学工程
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分子生物学
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影像科学
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产品关联
DOI
PubMed
高影响因子
INDUSTRIAL CROPS AND PRODUCTS
·
2025
·
IF 6.2
Tengteng Yang,Wenquan Wang,Xiaoli Wang,Qiaowei Miao,Junhai Liu,Hansheng Wang,Lun Liu,Xiaohui Ji,Chenyang Wei
Camptothecin (CPT) has significant biological activity and has been extensively studied. This study established an efficient and green ultrasonic-assisted deep eutectic solvent (UAE-DES) and combined it with macroporous resin purification technology to extract and purify CPT and 10-hydroxycamptothecin (HCPT) from Camptotheca acuminata fruit. In total, 33 natural DES were prepared, among which choline chloride-1,4-butanediol was the most effective. The single-factor and response surface optimization extraction experiments were carried out to determine optimal conditions as follows: ultrasonic time = 27 min, solid-liquid ratio = 1:35 g/mL, ultrasonic temperature = 70 °C, DES moisture content, = 29 %, and total extraction rate = 0.1318 %. Furthermore, the scanning electron microscopy revealed that the UAE-DES treatment significantly disrupted the cell-wall structure of C. acuminata fruits, promoting the release of the target constituents. Moreover, AB-8-type macroporous resin was employed to optimize adsorption and desorption, which optimized 63.4 % and 77.3 % adsorption and desorption of CPT and HCPT, respectively. Density functional theory (DFT) was employed for assessing electrostatic potential (ESP), complexation energy, and reduced density gradient (RDG), to identify the non-covalent interactions between DES, conventional solvent ethanol, and CPT-like compounds during the extraction process. This study comprehensively explained the extraction mechanism and confirmed that DES had better extraction potential and good biocompatibility. These findings provide a theoretical basis and technical support for the green and efficient extraction and purification of CPT-like compounds.
研究领域:
天然产物化学
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药物分析
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植物药学
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绿色化学
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分子互作机制
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产品关联
DOI
高影响因子
Pharmaceutics
·
2024
·Vol. 16
·期 10
·1327
·
IF 4.9
Huiping Zhang,Liang Li,Wei Li,Hongxia Yin,Huiyun Wang,Xue Ke
Background:CPT is a pentacyclic monoterpene alkaloid with a wide spectrum of antitumor activity. Its clinical application is restricted due to poor water solubility, instability, and high toxicity. We developed a new kind of multifunctional micelles to improve its solubility, reduce the side effecs, and obtain enhanced antitumor effects.Methods:We constructed HA-CPT nano-self-assembly prodrug micelles, which combined the advantages of pH-sensitivity, redox-sensitivity, and active targeting ability to CD44 receptor-overexpressing cancer cells. To synthesize dual sensitive HA-CPT conjugates, CPT was conjugated with HA by pH-sensitive histidine (His) and redox-sensitive 3,3′-dithiodipropionic acid (DTPA). In vitro, we studied the cellular uptake and antitumor effect for tumor cell lines. In vivo, we explored the bio-distribution and antitumor effects of the micelles in HCT 116 tumor bearing nude mice.Results:The dual-sensitive and active targeting HA-His-ss-CPT micelles was proved to be highly efficient in CPT delivery by the in vitro cellular uptake study. The HA-His-ss-CPT micelles escaped from endosomes of tumor cells within 4 h after cellular uptake due to the proton sponge effect of the conjugating His and then quickly released CPT in the cytosol by glutathione (GSH). In mice, HA-His-ss-CPT micelles displayed efficient tumor accumulation and conspicuous inhibition of tumor growth.Conclusions:The novel, dual-sensitive, active targeting nano-prodrug micelles exhibited high efficiency in drug delivery and cancer therapy. This “all in one” drug delivery system can be realized in an ingenious structure and avoid intricate synthesis. This construction strategy can illume the design of nanocarriers responding to endogenous stimuli in tumors.
研究领域:
药学
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纳米技术
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癌症治疗
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Xiaobing Liang,Jiaxin Li,Zhihui Li,Yibin Lin,Hailiang Li,Duoqu Chen,Yonghui Xiao,Wenjing Lin,Chufen Yang,Guobin Yi
Photo redox atom transfer radical polymerization (ATRP) represents an excellent technique for forming multifunctional polymers. However, there was little report on photo redox ATRP of graphene quantum dots (GQDs). Herein, we reported that introduced GQDs to ATRP in DMF solvent for the first time, significantly reducing the amount of copper catalyst (<500 ppm) required for the synthesis of alkali lignin-poly( N -isopropylacrylamide)-poly( N , N -dimethylaminoethyl methacrylate)-poly(poly(ethylene glycol) methyl ether methacrylate) (AL-(PNIPAM-PDMAEMA-PPEGMA) 2 ). The copolymer had molecular weight of 46,884 and polydispersity index (PDI) of 1.07. The micelles self-assembled from AL-(PNIPAM-PDMAEMA-PPEGMA) 2 in aqueous solution served as an excellent template for the simultaneous in situ preparation of silver nanoparticles (AgNPs) and the encapsulation of the hydrophobic anticancer drug camptothecin (CPT). By adjusting the mole ratio of [DMAEMA]:[AgNO 3 ], a series of AgNPs with controllable sizes (2.5–20.6 nm) could be obtained. AL-(PNIPAM-PDMAEMA-PPEGMA) 2 @Ag@CPT exhibited temperature and pH-sensitive release properties, releasing 80 % of the drug in an acidic and 37 °C tumor environment within 120 h. Furthermore, 150 μg/mL AL-(PNIPAM-PDMAEMA-PPEGMA) 2 @Ag@CPT effectively killed 75 % of cells within 48 h. 800 μg/mL AL-(PNIPAM-PDMAEMA-PPEGMA) 2 @Ag@CPT demonstrated highly efficient antibacterial effects. All these results suggest its potential application value in synergistic antitumor and antibacterial treatment system.
研究领域:
材料科学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2018
·Vol. 6
·期 11
·1678-1687
·
IF 4.776
Jiao-Yang Li,Liang Qiu,Xiao-Fei Xu,Cai-Yuan Pan,Chun-Yan Hong,Wen-Jian Zhang
A hybrid drug delivery system was successfully fabricated by attaching a camptothecin (CPT)-based polymeric prodrug onto the surface of silver nanoparticles (AgNPs). PEG was employed as a macro-RAFT agent in RAFT polymerization to synthesize a branched star copolymer, to which CPT is linked through the photo-responsive o-nitrobenzyl linkage. In vitro tests indicate that the fluorescence of CPT in the polymeric prodrug is quenched by AgNPs based on the nanomaterial surface energy transfer (NSET) effect and the fluorescence recovers when the CPT molecules are released from hybrid nanoparticles. Thus, the variation of fluorescence intensity is bound up with the drug release behaviours, which may enable this AgNP-based drug delivery system to trace the intracellular drug release process and observe the distribution of released CPT in cells.
研究领域:
生物医学工程
·
药剂学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 6.8
Chaoming Wang,Jing Zhang,Dongping Wang,Shengle Chen,Qi Yuan,Ruijuan Yin,Guiyang Yao,Xin Qi,Jing Li,Tao Jiang
Peptide–drug conjugates (PDCs) targeting integrin αvβ3 represent a promising strategy for tumor-targeted therapies. We designed and synthesized a series of integrin αvβ3-selective PDCs (PDC-1 to PDC-5) using a 1,3,5-triazine-based linker to conjugate the camptothecin derivative with the c(RGDfC) peptide. Among these, PDC-2 exhibited high stability in plasma, selective internalization via integrin αvβ3, efficient cell binding, and potent cytotoxicity. Additionally, it induced apoptosis of A549 and AsPC-1 cells and inhibited their adhesion, migration, and invasion in a concentration-dependent manner. Mechanistically, PDC-2 dually inhibits Survivin protein expression and the PI3K/AKT/mTOR signaling pathway. In A549 and AsPC-1 xenograft models, PDC-2 demonstrated superior tumor growth inhibition, reduced systemic toxicity, and enhanced tumor specificity compared to FL118. Pharmacokinetically, it enabled a sustained release of FL118, extending its half-life by 3.4-fold and promoting targeted tumor accumulation, positioning it as a promising therapeutic for lung and pancreatic cancers.
研究领域:
肿瘤学
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药学
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分子靶向治疗
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药物递送
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癌症生物学
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药物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Jing-Bo Yang,De-Zhong Xu,Zi-Han Zhang,Xi Zhang,Zhi-Xuan Ren,Zhong-Lin Lu,Rui Liu,Yang Liu
Maximizing drug cargo carrying capacity in blood circulation, controlling the in vivo fate of nanoparticles, and precisely drug release to tumor targets are the main aims of multifunctional nanomedicine-based antitumor therapy. Here we combined macrocyclic polyamine di(triazole-[12]aneN3) (M) and chemical drug camptothecin (CPT, C) through photosensitizer 1,1-dicyano-2-phenyl-2-(4-diphenylamino) phenyl-ethylene (DT) containing the cleavable disulfide (S) linkage as an all-in-one theranostic nanoprodrug, MDTSC. The corresponding compound with carbon chain (C) linkage, MDTCC, was also prepared for a comparison study. MDTSC showed the ability to carry plasmids, including the p53 tumor suppressor gene, to form lipoplexes with a size of ∼150 nm. Further addition of DOPE-PEG2k resulted in the hybrid lipoplexes MDTSC/DOPE-PEG2k@DNA, which showed good stability in blood circulation and good biocompatibility to normal cell lines. Experiments demonstrated that the hybrid lipoplexes were able to realize the successful cellular uptake and endosomal escape, to generate ROS under visible light irradiation as well as to trigger the localized release of CPT and the plasmid encoding p53 in tumor cells. In vitro, the hybrid lipoplexes showed better EGFP expression than the commercial Lipo2000, and markedly reduced tumor cell proliferation and migration rate irrespective of whether the BxPC-3 cell lines were grown on plates or 3D tumor spheroids. In vivo, the hybrid lipoplexes showed effective anticancer activity by reducing the BxPC-3 pancreatic tumor growth by 99% through the synergetic combination of chemotherapy, photodynamic therapy, and gene therapy. This research represented the first example of using a cocktail of three therapeutic approaches to achieve cooperative and effective anti pancreatic cancer treatment in vivo and in vitro.
研究领域:
纳米医学
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肿瘤学
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药学
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诊疗学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
CARCINOGENESIS
·
2019
·Vol. 41
·期 6
·804-816
·
IF 4.004
Wang Kai,Tu Yanbei,Wan Jian-Bo,Chen Meiwan,He Chengwei
Autophagy is an evolutionarily conserved mechanism to protect the cells from unfavorable environmental conditions. Inhibition of autophagy has been contemplated as a novel strategy to enhance anticancer efficacy of existing chemotherapeutic agents. We previously reported that pulsatilla saponin D (PSD) was a potent autophagy inhibitor. However, its anticancer potential as adjuvant and underlying mechanisms are still unknown. In this study, we identified that PSD induced the formation of autophagosome in MCF-7 and MDA-MB-231 breast cancer cells. However, PSD alone and particularly co-treatment with camptothecin remarkably increased p62 protein levels, indicating that PSD strongly inhibited the autophagic cargo degradation. The mechanistic study indicated that PSD profoundly abolished the co-localization of EGFP-LC3 and lysosomal-specific probe LysoTracker Red, suggesting that the autophagosome–lysosome fusion was blocked by PSD, which is similar to the action of chloroquine. In addition, PSD significantly increased lysosomal pH and inhibited the activation of lysosomal cathepsins in both breast cancer cell lines. Furthermore, the accrued p62 resulted in accumulation of ubiquitinated proteins owing to the interaction with p62 and delivery to the malfunctioned autophagosome by PSD. Finally, we demonstrated that PSD synergistically enhanced the anticancer activity of camptothecin (CPT) in cultured breast cancer cells and in mouse xenograft tumor models. Our results indicated that PSD inhibited autophagic flux via blocking autophagosome–lysosome fusion and lysosomal acidification, which may confer a synergistic anti-breast cancer activity of PSD and CPT.
研究领域:
肿瘤学
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2017
·
IF 5.401
Qiong-Qiong Ren,Jing Wu,Wen-Chao Zhang,Chang Wang,Xin Qin,Guo-Chang Liu,Zhen-Xin Li,Yi Yu
Single-walled carbon nanotubes (SWCNTs), horseradish peroxidase (HRP), and 1-butyl-3-methylimidazolium tetrafluoroborate (BMIM·BF 4 ) were employed to construct a cellular H 2 O 2 sensor based on direct electron transfer. At a working potential of −0.35 V, HRP-BMIM·BF 4 /SWCNTs/CFUME showed a dynamic range of up to 10.2 μM with a low detection limit of 0.13 μM (S/N = 3) and a high sensitivity of 4.25 A/M cm 2 . The apparent Michaelis-Menten constant ( K m,app ) was estimated to be as low as 15.4 μM, which suggested that HRP molecules entrapped in the BMIM·BF 4 and SWCNTs immobilized at the carbon fiber ultramicroelectrode maintained a very high affinity. Because of the extremely small dimension and low working potential, HRP-BMIM·BF 4 /SWCNTs/CFUME enabled direct amperometric real-time monitoring of H 2 O 2 in HeLa cells treated with the anticancer drug, camptothecin, without requiring complex data processing and extra surface coatings to prevent interference. HRP-BMIM·BF 4 /SWCNTs/CFUME testing clearly showed that the H 2 O 2 level significantly increased in HeLa cells under camptothecin stress. When HeLa cells were cultured in medium without camptothecin, the H 2 O 2 level remained stable during the whole measurement process. These results indicate that HRP-BMIM·BF 4 /SWCNTs/CFUME could be a powerful tool for real-time investigation of cellular H 2 O 2 level, especially under anticancer drug stress. This method could provide in-depth insights regarding the occurrence, development, and apoptosis of tumors.
研究领域:
分析化学
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生物医学
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2022
·
IF 8.039
Jiaqi Zhou,Xiaojian Bian,Zigui Kan,Zilong Cai,Yuxuan Jiang,Zike Wang,Yuanyuan Li,Wei Shi,Hai Qian
To enhance the affinity of the human epidermal growth receptor 2 (HER2) targeted peptide developed previously, bispecific fusion peptides P1GCGT1 and P1GCGCGT1 were designed using an in silico approach. Molecular dynamic simulation showed that both peptides strongly interacted with HER2 domains II and IV. Compared with peptides targeting each single domain, P1GCGT1 and P1GCGCGT1 could bind to HER2 more significantly and targeted HER2-positive cells specifically. Additionally, both peptides were used to generate peptide–drug conjugates with camptothecin (CPT), among which I-1 and I-4 were screened for enhanced cellular activity and selectivity. Biological evaluation demonstrated that I-1 and I-4 induced cell apoptosis, promoted cell cycle arrestin S-phase, and inhibited Topo I activity. The binding affinity assay and confocal analysis revealed that I-1 and I-4 were effective at targeting HER2. Moreover, I-1 and I-4 showed better stability than single targeting peptide and presented enhanced antitumor activity and safety than CPT in tumor-bearing mice.
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产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2025
·
IF 26.8
Yinghao Ding,Xueying Zhu,Jian Wen,Junchao Xiong,Shengyi Zhang,Zhimou Yang,Zhi-Wen Hu
Antigen presentation deficiency restricted by class I major histocompatibility complex (MHC-I) causes low antigenicity and antigen escape in tumors, thereby limiting T-cell immunotherapy outcomes. Here, a combined tumor immunotherapy is developed, in which tumors can present exogenous non-tumor antigens, and adoptively transferred CD8 + T cells specific for these antigens are re-targeted to attack tumors. The approach leverages a cascade-responsive peptide self-assembly to co-deliver suitable antigens and the chemotherapeutic drug camptothecin (CPT) to tumors. As a proof-of-concept, to re-target ovalbumin (OVA)-specific OT-I CD8 + T cells against tumors, PSA (Nap-GFFpYE-ss-Ag) and CPSA (CPT-GFFpYE-ss-Ag) are constructed, containing an OVA-derived epitope OVA 257-264 and/or CPT. The design enables the release of a unique N-terminal extended OVA 257-264 and CPT into the cytosol. As a result, the extended antigen is efficiently presented on the tumor surface by MHC-I, and CPT further enhances this presentation. When combined with adoptively transferred OT-I CD8 + T cells, the approach effectively facilitates CD8 + T cell infiltration and tumor inhibition. Additionally, CPSA treatment sensitizes immune responses to programmed cell death-ligand 1 (PD-L1) blockade, allowing the approach to synergize with an anti-PD-L1 antibody for improved tumor eradication.
研究领域:
肿瘤免疫学
·
纳米医学
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药物递送系统
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免疫治疗
·
分子自组装
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）