Biomaterials Science
·
2022
·Vol. 10
·期 5
·1292-1303
·
IF 7.59
Zian Wang,Xuan Wang,Hua Yu,Meiwan Chen
Camptothecin (CPT) is a potent broad-spectrum antitumor agent with efficient therapeutic effect for various cancers. However, its application in glioma therapy has been impeded by the tumor immunosuppressive environment and blood–brain barrier (BBB)-associated drug delivery challenges. Herein, neurotransmitter analogs-modified liposomes (NTs-LIP) were prepared by doping lipidized tryptamine (Tryp) to co-deliver CPT and curcumin (CUR) for improved chemo-immunotherapy in glioma. The introduction of Tryp promotes the delivery efficiency of CPT and CUR across the BBB. CPT inhibits cell proliferation after cellular uptake of NTs-LIP, the combination of which with CUR downregulates the elevated expression of the programmed cell death 1 ligand 1 (PD-L1) caused by CPT to prevent the inactivation of T-cells and synergistically enhance chemo-immunotherapy efficacy. Furthermore, both Tryp and CUR interfere with the indoleamine 2,3-dioxygenase (IDO) pathway to reduce regulatory T cell (Treg)-mediated immunosuppression, exhibiting the potential to combine with PD-L1 inhibition for synergistic antitumor immunity. Taken together, this platform contributes towards targeted delivery and alleviation of the immunosuppressive environment in glioma therapy.
研究领域:
药理学
·
神经科学
·
肿瘤学
·
纳米技术
·
免疫疗法
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2020
·
IF 8.758
Zhaopei Guo,Lin Lin,Kai Hao,Dianwei Wang,Feng Liu,Pingjie Sun,Haiyang Yu,Zhaohui Tang,Meiwan Chen,Huayu Tian,Xuesi Chen
For effective antitumor treatment, it is important to increase the water solubility of hydrophobic antitumor drugs and improve their cell absorption efficiency and nuclear transmission capacity. Here, we use endogenous hydrophilic arginine to modify camptothecin (CPT) to increase its water solubility. Surprisingly, the modified CPT can self-assemble into helical nanofibers through intermolecular π–π stacking and hydrophilic–hydrophobic interactions. Prodrug-based nanofibers were better endocytosed into the nucleus than their nonassembled CPT. Moreover, in vivo, such nanofibers had a longer blood circulation time and a better ability to accumulate in the tumor site. Further, we found that the cationic nanofibers can be combined with the anionic cisplatin–polyglutamic acid through electrostatic interaction to achieve a combined antitumor effect. This provides a new idea for achieving more effective cancer chemotherapy effects.
研究领域:
药学
·
生物医学工程
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF FLUORESCENCE
·
2017
·Vol. 27
·期 4
·1467-1477
·
IF 1.461
Ren Ting,Wang Zechun,Zhang Lijiao,Wang Ning,Han Xinxin,Wang Ruiyong,Chang Junbiao
In this work, the interaction between camptothecin (CPT) analogs and fat mass and obesity associated (FTO) was investigated using spectroscopy and molecular docking. From the experimental results, it was found that the CPT analogs caused the fluorescence quenching of FTO through a static quenching procedure. The binding constants and thermodynamic parameters at three different temperatures, the number of binding sites were obtained, which suggested that the hydrophobic interaction and electrostatic force played major role in the reaction between CPT analogs and FTO. Results revealed that 10-hydroxycamptothecin was the strongest quencher.
研究领域:
生物化学
·
药物化学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL SCIENCES
·
2015
·
IF 2.59
Ruixin Li,Chang Shu,Wei Wang,Xiaoliang Wang,Hui Li,Danke Xu,Wenying Zhong
ABSTRACT 10-Hydroxy camptothecin (HCPT) has been proven to be a cell cycle-specific chemotherapeutic agent, which is a necessary choice to inhibit tumor residue growth and prevent tumor metastasis after surgery. But it suffers from light decomposition, poor solubility, relatively low bioavailability, and some side effects, which are the major obstacles toward its clinical use. Integration of hydrophobic HCPT with hydrophilic hydrogel is a facile approach to change the disadvantageous situation of HCPT. In this study, a novel supramolecular hydrogelator with improved synthetic strategy was triggered by chemical hydrolysis, and then self-assembled to hydrogel. Taking advantage of the high-equilibrium solubility of HCPT in hydrogelator solution, this hydrogel was utilized to load HCPT via encapsulation as an effective carrier. HCPT hydrogels were characterized by several techniques including transmission electronic microscopy , rheology, and UV spectroscopy. In vitro release experiment indicated HCPT hydrogel could maintain long term and sustained release of HCPT at high accumulated rate. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay showed that HCPT hydrogel had an optimized anticancer efficacy. Besides, with prominent physical properties of carrier, HCPT hydrogel possessed satisfactory stability, syringeability, and recoverability, demonstrating itself as a potential localized injectable drug delivery system . © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:2266–2275, 2015
研究领域:
药学
·
药物递送系统
·
癌症治疗
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2018
·
IF 5.158
Pierre Dramou,Meriem Fizir,Abdoh Taleb,Asma Itatahine,Nasiru Sintali Dahiru,Yamina Ait Mehdi,Liu Wei,Jingyi Zhang,Hua He
In this research, to achieve enhanced intracellular uptake of anticancer drug carriers for efficient chemotherapy, folic acid conjugated chitosan oligosaccharides assembled magnetic halloysite nanotubes (FA-COS/MHNTs) have been tailored as multitask drug delivery system towards camptothecin (CPT). Besides magnetic targeting, the nanocomposites have been reacted with folate complex in order to selectively target cancer cells over expressing the folic acid receptor. HNTs showed to have a high storage capacity of CPT. In vitro, the release results indicated that CPT outflow from the nanocarriers at pH 5 was much greater than that at both pH 6.8 and 7.4. MTT assays showed that the CPT-loaded nanocarriers exhibited stronger cell growth inhibitory against colon cancer cell. Furthermore, nanocarriers gained specificity to target cancer cells because of the enhanced cell uptake mediated by FA moiety and presence of COS. Therefore, the rational designed HNTs nanocarrier for chemotherapy drug showed great potential as tumor-targeted drug delivery carrier.
研究领域:
生物医学工程
·
肿瘤学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2017
·
IF 7.504
Xueqiong Du,Yue Sun,Mingzu Zhang,Jinlin He,Peihong Ni
Polyphosphoesters (PPEs), as potential candidates for biocompatible and biodegradable polymers, play an important role in material science. Various synthetic methods have been employed in the preparation of PPEs such as polycondensation, polyaddition, ring-opening polymerization, and olefin metathesis polymerization. In this study, a series of linear PPEs has been prepared via one-step Michael addition polymerization. Subsequently, camptothecin (CPT) derivatives containing disulfide bonds and azido groups were linked onto the side chain of the PPE through Cu(I)-catalyzed azidealkyne cyclo-addition “click” chemistry to yield a reduction-responsive polymeric prodrug P(EAEP-PPA)-g-ss-CPT. The chemical structures were characterized by nuclear magnetic resonance spectroscopy, gel permeation chromatography, Fourier transform infrared, ultraviolet–visible spectrophotometer, and high performance liquid chromatograph analyses, respectively. The amphiphilic prodrug could self-assemble into micelles in aqueous solution. The average particle size and morphology of the prodrug micelles were measured by dynamic light scattering and transmission electron microscopy, respectively. The results of size change under different conditions indicate that the micelles possess a favorable stability in physiological conditions and can be degraded in reductive medium. Moreover, the studies of in vitro drug release behavior confirm the reduction-responsive degradation of the prodrug micelles. A methyl thiazolyl tetrazolium assay verifies the good biocompatibility of P(EAEP-PPA) not only for normal cells, but also for tumor cells. The results of cytotoxicity and the intracellular uptake about prodrug micelles further demonstrate that the prodrug micelles can efficiently release CPT into 4T1 or HepG2 cells to inhibit the cell proliferation. All these results show that the polyphosphoester-based prodrug can be used for triggered drug delivery system in cancer treatment.
研究领域:
材料科学
·
生物医学工程
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOID AND POLYMER SCIENCE
·
2014
·Vol. 292
·期 5
·1061-1072
·
IF 2.41
Luo Yan-Ling,Yang Xiao-Li,Xu Feng,Chen Ya-Shao,Zhao Xu
pH-sensitive poly(methacrylic acid)- block -hydroxyl-terminated polybutadiene- block -poly(methacrylic acid) block copolymers were synthesized by atom transfer radical polymerization of t -butyl methacrylate and follow-up acidolysis. The copolymers can spontaneously assemble into stable and nearly spherical micelle aggregates in aqueous solution, with hydrodynamic diameters ( D
h
) from 51 to 92 nm and critical micelle concentration of 3.90–7.76 mg L −1 . Z eta potentials were found to be increased with increasing (monomer)/(initiator) molar ratios. A pH-dependent phase behavior is produced at approximately 5.4–5.6, as determined by D
h
and I
335 / I
332 fluorescence intensity ratios. The in vitro camptothecin (CPT) release was compositional and pH dependent, and the cumulative CPT release below pH 7.2 was higher than that in pH 7.4. They could inhibit the premature burst CPT release. The copolymer micelles were low in cytotoxicity even at a micellar concentration of 800 mg L −1 , and therefore they may be used as potential drug-delivery carriers.
ᅟ
研究领域:
药剂学
·
高分子化学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
Acta Biomaterialia
·
2017
·
IF 6.319
Yue Yan,Jie Fu,Tianfu Wang,Xiuyang Lu
As efficient drug carriers, stimuli-responsive mesoporous silica nanoparticles are at the forefront of research on drug delivery systems. An acid-responsive system based on silyl ether has been applied to deliver a hybrid prodrug. Thiol-ene click chemistry has been successfully utilized for tethering this prodrug to mesoporous silica nanoparticles . Here, by altering the steric bulk of the substituent on the silicon atom, the release rate of a model drug, camptothecin, was controlled. The synthesized drug delivery system was investigated by analytical methods to confirm the functionalization and conjugation of the mesoporous silica nanoparticles. Herein, trimethyl silyl ether and triethyl silyl ether were selected to regulate the release rate. Under normal plasma conditions (pH 7.4), both types of camptothecin-loaded mesoporous silica nanoparticles (i.e., MSN-Me-CPT and MSN-Et-CPT) did not release the model drug. However, under in vitro acidic conditions (pH 4.0), based on a comparison of the release rates, camptothecin was released from MSN-Me-CPT more rapidly than from MSN-Et-CPT. To determine the biocompatibility of the modified mesoporous silica nanoparticles and the in vivo camptothecin uptake behavior, MTT assays with cancer cells and confocal microscopy observations were conducted, with positive results. These functionalized nanoparticles could be useful in clinical treatments requiring controlled drug release . Statement of Significance As the release rate of drug from drug-carrier plays important role in therapy effects, trimethyl silyl ether (TMS) and triethyl silyl ether (TES) were selected as acid-sensitive silanes to control the release rates of model drugs conjugated from MSNs by thiol-ene click chemistry. The kinetic profiles of TMS and TES materials have been studied. At pH 4.0, the release of camptothecin from MSN-Et-CPT occurred after 2 h, whereas MSN-Me-CPT showed immediate drug release. The results showed that silyl ether could be used to control release rates of drugs from MSNs under acid environment, which could be useful in clinical treatments requiring controlled drug release .
研究领域:
药学
·
纳米医学
·
生物材料
✓ 已验证
DOI
PubMed
高影响因子
Pharmaceutics
·
2026
·Vol. 18
·期 6
·649
·
IF 6.9
Congyi Zhang,Haotian Wu,Xiaotong Chen,Wenze Yin,Shizhuan Huang,Dixiang Wen,Xueting Song,Xiaoyan Xu,Changmei Zhang,Sheng Tai
Background/Objectives: This study aimed to develop a novel tumor-associated macrophage (TAM)-targeting nanoplatform to improve the solubility and bioavailability of camptothecin (CPT) and achieve active targeted drug delivery for enhanced anti-tumor immunotherapy.Methods: We constructed a sialic acid-disulfide bond-camptothecin (SA-SS-CPT) nanowire system. Sialic acid was used as a targeting ligand to specifically recognize the overexpressed Siglec-E receptor on TAMs. Upon cellular internalization, the disulfide bond was designed to respond to intracellular glutathione (GSH), enabling controlled drug release.Results: The SA-SS-CPT nanowires significantly improved CPT solubility and enabled targeted delivery to TAMs. Following GSH-responsive cleavage and CPT release, the nanowires induced DNA damage in TAMs, activating the cGAS-STING signaling pathway. This promoted TAM polarization toward the M1 phenotype, enhanced pro-inflammatory and anti-tumor immune responses, and inhibited tumor immune escape. Furthermore, SA-SS-CPT synergistically improved the efficacy of PD-L1 blockade immunotherapy, remodeling the tumor immune microenvironment.Conclusions: The SA-SS-CPT nanoplatform effectively targets TAMs, repolarizes them to an anti-tumor M1 phenotype, and activates the cGAS-STING pathway. It shows strong potential for overcoming tumor immune escape and synergizing with PD-L1 checkpoint blockade to achieve significant tumor clearance.
✓ 已验证
DOI
高影响因子
Scientific Reports
·
2025
·Vol. 15
·期 1
·1-16
·
IF 3.9
Wang Yuhe,Li Junfeng,Li Xuanda,Gao Bingmiao,Chen Jiao,Song Yun
This study investigates the binding interactions between bovine serum albumin (BSA) and camptothecin (CPT) drugs (camptothecin, 10-hydroxycamptothecin, topotecan, and irinotecan) using UV–Vis spectroscopy, fluorescence spectroscopy, three-dimensional fluorescence spectroscopy, and molecular docking techniques. The fluorescence quenching of BSA by CPT drugs follows a static mechanism, with binding constants (K b ) ranging from 4.23 × 10 3 M − 1 (CPT) to 101.30 × 10 3 M − 1 (irinotecan), demonstrating significant drug binding selectivity. Thermodynamic analysis reveals distinct interaction mechanisms: topotecan binding is driven by hydrogen bonding (ΔH = − 10.96 kJ·mol − 1 ) and hydrophobic interactions (ΔS = 0.066 kJ·mol − 1 ·K − 1 ), while irinotecan exhibits stronger binding dominated by electrostatic forces (ΔH = − 86.77 kJ·mol − 1 ) with significant entropy loss (ΔS = − 0.161 kJ·mol − 1 ·K − 1 ). Molecular docking confirms preferential binding at Sudlow site I of BSA, with hydrophobic interactions and hydrogen bonding as the primary driving forces. These findings provide a comprehensive understanding of CPT-BSA interactions, offering valuable insights for the design of albumin-based drug delivery systems with optimized pharmacokinetic profiles.
研究领域:
药理学
·
生物化学
·
药物设计
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MedChemComm
·
2012
·Vol. 3
·期 12
·1555-1561
·
IF 2.8
Haiqing Dong,Chunyan Dong,Yue Feng,Tianbin Ren,Zhonghai Zhang,Lan Li,Yongyong Li
Camptothecin (CPT), a broad-spectrum anticancer drug, is limited in the extensive applications for its extremely hydrophobic property and low physiological stability in clinical use. In this study, prodrug of PEGylated CPT bioconjugate was synthesized to address the above critical issues. The as-designed amphiphilic conjugate could self-assemble into core–shell nanomicelles to enhance the solubility of the CPT and simultaneously improve the stability by encapsulating CPT in the micellar core. Furthermore, the core–shell structure of nanomicelles affords the capability of combination drug delivery by loading other hydrophobic drugs in the core. Doxorubicin (DOX) was chosen as model for combination delivery by physical encapsulation method. It is demonstrated that DOX could be efficiently loaded with controlled release kinetics. Cellular uptake experiments show that this micelle based drug delivery system is able to be efficiently uptaken by cells to achieve combination delivery. In vitro cytotoxicity of the CPT micelles and the DOX-loaded system are evaluated respectively through cell cytotoxicity against Hela cells, the results show an obviously enhanced cytotoxicity over free CPT while the DOX-loaded system exhibit more potent inhibition on cell proliferation ascribed to the combined effect of physically entrapped DOX and chemical conjugated CPT.
研究领域:
药学
·
生物医学工程
·
肿瘤学
✓ 已验证
DOI
高影响因子
Nanomedicine
·
2021
·
IF 5.307
Jialing Dai,Mo Chen,Dongmei Xu,Huangjuan Li,Yingyu Qiao,Xue Ke,Tianyuan Ci
The aim of this study was to prepare small-molecule camptothecin (CPT) prodrugs and evaluate their effectiveness in colorectal carcinoma therapy. Prodrug nanoparticles (NPs) were physicochemically characterized and evaluated for their cytotoxicity in human colon cancer (HCT116) cell lines. The antitumor efficacy of the NPs was evaluated in HCT116 tumor-bearing mice. The prepared NPs exhibited high drug loading capacity (32% of CPT w/w) and also kept a high active lactone fraction of CPT (>85%) during circulation. The NPs were internalized into tumor cells efficiently compared with free drug and significantly enhanced the drug’s therapeutic efficacy. The developed small-molecule CPT prodrug NPs could be a promising strategy in the clinical therapy of colorectal carcinoma.
研究领域:
药学
·
肿瘤学
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）