Acta Biomaterialia
·
2016
·
IF 6.008
Maohua Chen,Yun Zhang,Zhoujiang Chen,Songzhi Xie,Xiaoming Luo,Xiaohong Li
Challenges remain to load and deliver two or multiple drugs of complementary effects for synergistic cancer therapies. In the current study, multiarmed amphiphilic copolymers of 4-arm poly(ethylene glycol) (PEG) and polyaspartate (PAsp) are created for conjugation of camptothecin (CPT) and condensation with tumor necrosis factor-α (TNF) plasmids. Diethylenetriamine (DET) is grafted on PAsp, and CPT is conjugated onto PAsp(DET) by disulfide linkages to form hydrophobic cores of micelles , followed by condensation with TNF plasmids to form micelleplexes. The cis -aconitic linkers are introduced between PEG and PAsp(DET) to remove PEG shells in response to acidic pH, resulting in destabilized micelleplexes and prompted endosomal escape into the cytosol. The micelleplex disintegration in response to reductive stimuli in the cytosol leads to an efficient CPT release and pDNA disassociation. The co-delivery of CPT with TNF plasmids enhances the gene transfection of micelleplexes at low N/P ratios, and shows synergetic cytotoxicities to tumor cells with 2.5 and 8 folds lower IC 50 s compared with those after treatment with CPT or TNF alone, respectively. The micelleplex treatment on 4T1 tumor models dramatically extends the animal survival and suppresses the tumor growth with 2.3 and 3 folds lower in volume compared with CPT or TNF treatment alone, respectively. Histological and biochemical analyses display TNF expressions in tumor tissues after micelleplex treatment, resulting in significantly larger necrotic regions in tumors, higher cell apoptosis rates , and no obvious sign of tumor metastasis in lungs compared with other treatment. Therefore, the multifunctional micelleplexes based on multiarmed PEG-PAsp(DET) copolymers offer the targeted drug/gene delivery, dually responsive drug/gene release and synergistic antitumor efficacy, holding great promises for combination therapies. Statement of Significance Micelleplexes are constructed from multiarmed amphiphilic copolymers with conjugation of captothecin (CPT) and condensation of tumor necrosis factor-α (TNF) plasmid. The pH/redox stimuli realize co-delivery of CPT and pDNA in a sequential manner of folate-mediated endocytosis , endosomal escape induced by PEG cleavage, reduction-sensitive release of CPT in cytosol, and pDNA release from disintegrated polyplexes after CPT release. Compared with CPT or TNF treatment alone, the micelleplexes achieve 2.5 and 8 folds higher cytotoxicities to tumor cells, and suppress the tumor growth with 2.3 and 3 folds lower in volume, respectively. It demonstrates a feasible strategy to develop multifunctional micelleplexes with simultaneous drug conjugation and pDNA condensation, dually responsive drug/gene release and synergistic antitumor efficacy, holding great promise for combinational therapies.
研究领域:
药剂学
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肿瘤学
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生物材料科学
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Kunpeng Liu,Binbin Jiao,Guan Zhang,Zhihua Gan,Shicong Lai,Zhenshan Ding,Qingsong Yu
Bladder cancer remains a significant clinical challenge, necessitating the development of innovative therapeutic strategies. Recent advancements have highlighted the potential of reactive oxygen species (ROS)-responsive drug delivery systems in cancer therapy. In this study, we introduce a novel treatment approach utilizing a ROS-responsive camptothecin (CPT) prodrug encapsulated within a chitosan nanocarrier, named CACPT. Cinnamaldehyde (CA), acting as a ROS generator, forms thioketal bonds with CPT to create a prodrug that responds selectively to the elevated ROS levels within the tumor microenvironment. Upon exposure to high ROS conditions, these thioketal bonds are cleaved, resulting in the simultaneous release of CPT and CA. The liberated CA further enhances ROS production, establishing a positive feedback loop that amplifies the therapeutic effect. The use of amphiphilic chitosan nanocarriers enhances the retention and penetration of the prodrug within bladder tissue, optimizing its therapeutic potential. Our experimental findings demonstrate that this self-enhanced ROS-responsive release promotes increased cellular uptake and significantly enhances the anticancer efficacy of CACPT. These results position CACPT as a promising candidate for intravesical therapy in bladder cancer, potentially overcoming current limitations in treatment options. The innovative combination of ROS-responsive mechanisms and chitosan nanocarriers represents a paradigm shift in bladder cancer therapeutics, offering a multifaceted approach with substantial promise for clinical translation.
研究领域:
肿瘤学
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药剂学
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生物材料学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2012
·
IF 3.456
Junping Zeng,Haitao Huang,Shiyuan Liu,Haibo Xu,Jin Huang,Jiahui Yu
This research is aimed to develop a kind of hollow nanosphere based on β-cyclodextrin-grafted α, β-poly(aspartic acid) (β-CD- graft -PAsp) as drug carrier to enhance the stability of camptothecin (CPT) in aqueous media. Firstly, mono(6-(2-aminoethyl) amino-6-deoxy)-β-cyclodextrin (β-CDen) was synthesized by a substitution reaction between mono-6-deoxy-6-(p-tolylsulfonyl)-β-cyclodextrin (6-OTs-β-CD) and ethylenediamine; and then, the five-member rings in poly( l -succinimide) (PSI) were successively opened by β-CDen to obtain β-CD- graft -PAsp. The synthesized β-CD- graft -PAsp was found to form the unique hollow nanosphere with the internal hole of about 17 nm and many β-CD cavities of 0.7 nm interspersed on the shell. The drug-loading behavior of the hollow nanosphere was also evaluated by using CPT as guest molecule of β-CD. It was worth of note that the β-CD- graft -PAsp hollow nanosphere as carrier enhanced the stability of CPT in aqueous media, and the CPT from the β-CD- graft -PAsp hollow nanosphere displayed a sustained release profile and hence resulted in the essential decrease of cytotoxicity to L929 cell line. Furthermore, almost no cytotoxicity of the β-CD- graft -PAsp is desirable for the application of drug carrier. As a result, the β-CD- graft -PAsp hollow nanosphere showed a great potential as the carrier of CPT.
研究领域:
药学
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纳米技术
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材料科学
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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
Chemistry-An Asian Journal
·
2025
·
IF 3.3
Xiaoqing Jia,Yingfeng Wei,Xinyuan Zhang,Qiuping Gu,Youshun Liu,Shige Wang,Chunping Zhu
A dual-drug-loaded γ-polyglutamic acid (γ-PGA) hydrogel was synthesized, integrating third-generation dendrimers (G3) as cross-linkers for the simultaneous encapsulation of hydrophilic doxorubicin (DOX) and hydrophobic camptothecin (CPT). This hydrogel, formed via an efficient EDC/NHS-mediated reaction, demonstrated a biocompatible, porous, and pH-responsive network. The hydrophobic core of G3 significantly enhanced CPT loading, while γ-PGA facilitated effective DOX incorporation. Controlled drug release was observed, with DOX releasing faster in acidic tumor-like environments, optimizing therapeutic impact at the tumor site. In vitro studies highlighted the hydrogel's high biocompatibility and synergistic anticancer efficacy, reducing CT26 colon cancer cell viability more effectively than single-drug systems. In vivo experiments confirmed substantial tumor suppression, prolonged survival, and the absence of systemic toxicity in murine models. These results underscore the potential of this dual-drug delivery platform as a robust, multifunctional system for cancer therapy. The biocompatibility, degradability, and tailored drug release characteristics make this hydrogel a promising candidate for clinical translation, offering a novel solution for enhancing cancer treatment efficacy while minimizing side effects.
研究领域:
生物材料
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药物递送
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肿瘤学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2018
·
IF 3.997
Chaoyang Li,Hua Zhang,Xianfeng Gong,Qiang Li,Xueling Zhao
The chemical stability, good biocompatibility and high drug loading capacity of zinc oxide nanoparticles (ZnO NPs) and their biomedical potentials make them a promising candidate for drug delivery. The aim of this study was to develop and assess a simple procedure for surface functionalization of ZnO NPs by N-acetyl- l -cysteine (NAC) for anticancer camptothecin (CPT) delivery. NAC capped ZnO NPs were successfully made using ZnCl 2 and NaOH in the presence of NAC. CPT was covalently conjugated to the surface of as-synthesized ZnO-NAC NPs. To characterize the synthesized conjugate product (ZnO-NAC-CPT NPs), X-ray diffraction, Fourier Transform Infrared spectroscopy, transmission electron microscopy, scanning electron microscopy, and dynamic light scattering method were used. Our results indicated that the ZnO-NAC-CPT NPs exhibit near-spherical morphology and uniform dispersion with an average diameter of ∼70 nm. The hemolysis assay showed that ZnO-NAC-CPT NPs has almost no hemolytic activity. In addition, MTT cytotoxicity assessment on A549 lung cancer cells revealed a drop of IC 50 values from 1.17 μg/mL (free CPT) to 0.66 μg/mL (ZnO-NAC-CPT NPs). This result showed an augmented cancer-inhibitory effect of nanoconjugate complex. In conclusion, the novel ZnO-NAC-CPT NPs could be considered for new therapeutic endeavors.
研究领域:
纳米技术
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药学
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癌症研究
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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
BIOMEDICINE & PHARMACOTHERAPY
·
2016
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IF 2.326
Qin Tang,Fangling Ji,Jianli Guo,Jingyun Wang,Yachen Li,Yongming Bao
Chrysin , one of natural flavonoid compounds, has recently been found to possess anti-inflammatory, antiallergic and anticancer properties. To increase its anticancer effects, 5 chrysin derivates were synthesized on the base of DNA intercalator structure. The inhibiting effects of chrysin and its derivatives on cancer cells Hela, BGC823, MCF-7, HepG2, and normal cells HEK-293, were evaluated by MTT assays . 5-(2′-amino) phenyl-7-cyclohexanemethylchrysin (Ch-1), a unique chrysin derivate, killed all the cancer cells but kept above 60% survival rate in normal cells HEK-293 at 62.5 μM. Treated with chrysin from 250 μM to 500 μM, those cells were still maintained above 60% survival rate. The result of circular dichroism spectra showed that Ch-1 could intercalate DNA while chrysin had no effects on DNA. Interestingly, Hela cells survival rates were 95% and 10%, after treated with 20 μM and 30 μM of Ch-1, respectively. Both intrinsic and extrinsic apoptotic pathway were identified in regulating the cell death caused by Ch-1 in Hela cells. p53, the upstream regulator of apoptotic pathway were extremely significantly up-regulated in Hela cells treated with 25 μM Ch-1. Moreover, the inhibiting effects and apoptotic related proteins responses to Ch-1 on Hela cells were abolished after pre-treated with Pifithrin-α (Pft-α), a p53 inhibitor. So, p53-depedent apoptosis is the crucial factor governing the inhibiting effects of Ch-1 in Hela cells. Amazingly, Ch-1 at non-toxic concentration (2.5–10 μM) enhanced significantly anti-cancer effect of 10-hydroxy camptothecin (HCPT) on Hela, BGC823, and MCF-7 cells.
研究领域:
癌症研究
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药理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2023
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IF 10.2
Ka Hong Wong,Zhaopei Guo,Di Jiang,Xingzhi Zhou,Lizhu Lin,Denggao Zhao,Meiwan Chen
Nano drug delivery systems have made significant progress in delivering anticancer drugs camptothecin (CPT). However, many challenges for CPT delivery remain, including low drug loading efficiency, premature drug leakage, and poor cellular internalization. Herein, we report a novel dual-sensitive polypeptide-based micelle with remarkably high drug loading of CPT for cancer therapy. This self-assembled micelle possesses the following essential components for CPT: (1) pH-sensitive PEG (OHC-PEG-CHO) for prolonging blood circulation and allowing biocompatibility by shielding the cationic micelles, which can be detached under the tumor acidic microenvironment and facilitates the cellular uptake; (2) polypeptide polylysine-polyphenylalanine (PKF) synthesized via ring-opening polymerization for micelle formation and CPT analogue loading; (3) dimeric CPT (DCPT) with redox-sensitive linker for increasing CPT loading and ensuring drug release at tumor sites. Interestingly, the linear-like morphology of PEG-PKF/DCPT micelles was able to enhance their cellular internalization when compared with the spherical blank PKF micelles. Also, the anticancer efficacy of DCPT against lung cancer cells was significantly improved by the micelle formation. In conclusion, this work provides a promising strategy facilitating the safety and effective application of CPT in cancer therapy.
研究领域:
纳米医学
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癌症研究
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药剂学
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聚合物化学
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产品关联
DOI
PubMed
高影响因子
Advanced Therapeutics
·
2023
·
IF 4.6
XiaoJie Song,Kang-Li Lan,Yi-Fei Xue,Hong-Min Liu,Qi-Yan Lv,Zhen Zhao,Hui-Fang Cui
Camptothecin (CPT) is impeded by low solubility, non-tumor-targeting ability, and fast blood clearance. Self-assembly of hydrophobic drugs into nanostructures, especially nanoparticles (NPs), can improve their anti-cancer effects. In this study, arginine-glycine-aspartic acid (RGD), a hydrophilic and tumor-targeting peptide, is conjugated with CPT through a glutathione-cleavable disulfide bond. The synthesized amphiphilic molecule CPT-ss-RGD self-assembled into stable NPs in an aqueous solution with diameters of ≈86nm. They exhibited low critical aggregation concentrations, good stability, and glutathione responsiveness. They can be specifically taken up by CRC cells through RGD integrin-mediated uptake, and exhibit high toxicity to CRC cells and multicellular tumor spheroids. As expected, CPT-ss-RGD NPs prolonged the blood circulation time and enhanced the tumor accumulation of CPT, exhibiting excellent anti-tumor growth ability and few side effects. Thus, CPT-ss-RGD NPs have great clinical translational potential for CRC therapy. The successful self-assembly of the CPT-ss-RGD NPs provides a new method for the self-delivery of hydrophobic therapeutics in vivo.
研究领域:
药学
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纳米技术
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肿瘤学
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药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Liping Yin,Kaiyue Zhang,Weichen Sun,Yu Zhang,Yong Wang,Jianglei Qin
The self-healing hydrogels have important applications in biomedication as drug release carrier. In this research, the Doxorubicin (DOX) was coupled onto oxidized carboxymethylcellulose (CMC) (CMC-Ald) to fabricate self-healing hydrogel with intrinsic antitumor property and loaded with Camptothecin (CPT) for synergetic antitumor treatment. The DOX coupled CMC-Ald (CMC-AD) was reacted with poly(aspartic hydrazide) (PAH) to fabricate injectable self-healing hydrogel. The coupled DOX avoided the burst release of the drug and the 100 % CPT loaded hydrogel could take the advantages of both drugs to enhance the synergetic antitumor therapeutic effect. The in vitro and in vivo results revealed the CPT loaded CMC-AD/PAH hydrogel showed enhanced antitumor property and reduced biotoxicity of the drugs. These properties demonstrate that the CMC-AD/PAH hydrogel has great application prospects in biomedication.
研究领域:
生物医学工程
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药剂学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chinese Medicine
·
2023
·Vol. 18
·期 1
·1-14
·
IF 4.9
Guo Zhaopei,Wong Ka Hong,Li Enze,Zhou Xingzhi,Jiang Di,Gao Jiebing,Chen Meiwan
Background The integration of photodynamic therapy with a chemical drug-delivery system has displayed great potential in enhancing anticancer therapy. However, the solubility and non-specific biodistribution of both chemotherapeutic agents and photosensitizers continue to pose challenges that hinder their clinical applications.MethodA polypeptide-based nanoscale drug delivery system was fabricated to address the prementioned issues. An amphiphilic polymer was formed by conjugating the photosensitizer chlorin e6 (Ce6) onto a polypeptide poly-(L-lysine)-b-polyphenylalanine (PKF) for encapsulating the model drug dimeric camptothecin (DCPT), and the nanoparticles (PCD) with high drug loading efficiency were further modified with acid-sensitive polyethylene glycol (PEG) to yield the drug delivery sytem (PPCD).Results The DCPT and Ce6 encapsulation efficiency were analyzed as 99% and 73.5%, respectively. In phosphate-buffered saline (PBS) solution at a pH of 7.4, the PEG shell improved the stability of micelles and shielded their positive charge while in the acidic tumor microenvironment, the pH-sensitive PEG layer was removed to expose the cationic nanoparticles, thus facilitating the cellular uptake of PPCD micelles. Benefiting from the enhanced cellular internalization, the amount of intracellular reactive oxygen species (ROS) treated with PCD and PPCD micelles were obviously increased. Furthermore, the enhanced anti-cancer efficacy prompted by PPCD micelles was validated through cellular and animal study.Conclusion This study presents a promising method to promote the solubility and biodistribution of both chemotherapeutic agent and photosensitizer, thereby facilitating the further application of chemo-photodynamic cancer therapy.Graphical Abstract
研究领域:
癌症治疗
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纳米技术
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药剂学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2026
·
IF 5.1
Xincheng Sun,Changkang Li,Jimei Liu,Ridao Chen,Dawei Chen,Jungui Dai
The 6/5/6 to 6/6/5 ring system rearrangement from indole alkaloids strictosidine ( 1 ) and strictosamide ( 2 ) to quinoline alkaloid pumiloside ( 3 ) is an essential but unelucidated process in the biosynthesis of camptothecin, especially, the intermediates involved in the process have not been identified. Herein, the nonenzymatic conversions including spontaneous reaction from 1 to 2 , and light- or flavin-catalyzed skeletal rearrangement from 2 to 3 have been discovered. Particularly, the crucial biosynthetic intermediate strictosamide ketolactam ( 2a ) with dicarbonyl nine-membered ring involved in the conversion from 2 to 3 is obtained and structurally characterized. Moreover, the successive conversion from 1 to 3 is achieved in Nicotiana benthamiana . These findings not only provide a new insight into and better understanding for the biosynthesis of camptothecin with rare nonenzymatic reactions, also lay the foundation for further elucidation of the biosynthetic pathway of camptothecin.
✓ 已验证
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Chunying Li,Zidan Luo,Mengfei Tian,Qi Liang,Xiaofei Xie,Chunjian Zhao
Traditional solid phase extraction (SPE) suffers from a lack of specific adsorption. To overcome this problem, a combination of adsorption method and molecular imprinting technology by polydopamine modification was proposed to realize specific recognition of target compounds in SPE, which is of great significance to improve the separation efficiency of SPE. Cellulose hydrogel beads were prepared by dual cross-linking curing method and modified with polydopamine to make them hydrophilic and biocompatible. Subsequently, cellulose hydrogel-based molecularly imprinted beads (MIBs) were synthesized by surface molecular imprinting technology and used as novel column fillers in SPE to achieve efficient adsorption (34.16 mg·g −1 ) with specific selectivity towards camptothecin (CPT) in 120 min. The simulation and NMR analysis revealed that recognition mechanism of MIBs involved hydrogen bond interactions and Van der Waals effect. The MIBs were successful used in separating CPT from Camptotheca acuminata fruits, exhibiting impressive adsorption capacity (1.19 mg·g −1 ) and efficient recovery of CPT (81.54 %). Thus, an environmentally friendly column filler for SPE was developed, offering a promising avenue for utilizing cellulose-based materials in the selective separation of natural products .
研究领域:
材料科学
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分析化学
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天然产物分离
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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）