International Journal of Nanomedicine
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2020
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IF 5.115
Ting Zhou,Wei Zhang,Dongliang Cheng,Xin Tang,Jianfang Feng,Wei Wu
Purpose In this study, NK4-conjugated hydroxycamptothecin liposomes (NK4-HCPT-Lips) were prepared with the aim of improving drug targeting to the liver.Methods NK4-HCPT-Lips were prepared using the thin-film dispersion method. In vitro antitumor activities were evaluated by MTT assay. HCPT levels in plasma and tissues were determined via high-performance liquid chromatography (HPLC) with camptothecin as the internal standard, and the characteristics, pharmacokinetics, and bio-distribution of NK4-HCPT-Lips were evaluated.Results The liposomes showed a regular spherical-shaped morphology, and the entrapment efficiency and drug loading capacity reached 82.5 ± 2.4% and 3.01 ± 0.23%, respectively, with a particle size of 155.6 ± 2.6 nm and a zeta potential of −24.8 ± 3.3 mV. Inhibition effect experiments found that NK4-HCPT-Lips had a good inhibition on the HepG2 cells. Pharmacokinetic studies revealed an increase in the area under the curve and mean residence time as well as a decrease in plasma clearance (p < 0.05) of the NK4-HCPT-Lips compared to those of HCPT liposomes and a commercial HCPT injection. Tissue distribution studies showed that NK4-HCPT-Lips were present at high levels in the liver but were cleared from the kidneys.Conclusion These results demonstrate that NK4-HCPT-Lips possess excellent liver-targeting attributes, which could enhance the therapeutic effects of drug treatments for hepatic diseases.
研究领域:
药剂学
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肿瘤学
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肝脏疾病研究
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DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
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2026
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IF 7.3
Xinyue Zang,Peigen Wei,Chunxia Xu,Jiuyang Sun,Xiuling Yu,Deyin Wang,Zaixiang Zhang,Chang Liu,Feng Feng,Ruoping Wang,Yang Yang
The design of multimechanistic conjugates based on 10-hydroxycamptothecin (10-HCPT) offers a promising approach to reduce toxicity and enhance antitumor efficacy. We designed and synthesized a novel series of conjugates by linking melampomagnolide B (MMB) to 10-HCPT/SN-38 via diverse linkers. Among them, 6i1/6i2 exhibited remarkable anticolorectal cancer potency and minimal cytotoxicity toward normal THLE-2 cells. Mechanistic studies indicated that 6i1/6i2 could inhibit IκB kinase β (IKKβ), leading to the inhibition of p65 and IκBα phosphorylation, suppression of p65 nuclear translocation, and subsequent regulation of genes controlled by nuclear factor kappa-B (NF-κB). Additionally, they targeted topoisomerase I (Topo I), inducing DNA damage, reactive oxygen species (ROS) accumulation, mitochondrial membrane potential loss, and S-phase arrest. In a CT-26 xenograft model, 6i1 and 6i2 (5 mg/kg) potently suppressed tumor growth, achieving TGI rates of 89.9% and 95.4% without observable toxicity.
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PubMed
高影响因子
Biomedical Materials
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2024
·Vol. 19
·期 2
·025018
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IF 3.9
Antong Jiang,Teng Wang,Xiaoling Lu,Yuxiang Tian,Zihan Jiang,Bin Xu,Hanyuan Zhang,Weijun Fang
The application of both chemotherapy and ferrotherapy together has shown great potential in increasing the effectiveness of cancer treatment. To achieve such a combination, we herein have synthesized Fe3O4 core/MIL-100(Fe) shell nanocomposites (FM) that can be used for tumor chemo-ferroptosis combination therapy. In these nanocomposites, the anticancer drug 10-hydroxycamptothecin (HCPT) and iron ions could be co-delivered into tumors. On one hand, the released HCPT molecules can enter the cell nucleus and bind with DNA, resulting in induction of tumor cell apoptosis. On the other hand, the iron ions could react with H2O2 leading to the production of ROS through the Fenton reaction, thereby triggering tumor cell ferroptosis. Consequently, a superior antitumor effect was achieved through the combination of the apoptosis and ferroptosis. Additionally, the Fe3O4 core endowed FM with high performance for magnetic resonance imaging, which further provided novel avenues for imaging guidance therapy. Therefore, we anticipate that application of these nanocomposites could have great potential in the field of tumor therapy.
研究领域:
纳米技术
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癌症治疗
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磁共振成像
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材料科学
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DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL SCIENCES
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2016
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IF 2.641
Hongyan Zhu,Jie Cao,Sisi Cui,Zhiyu Qian,Yueqing Gu
ABSTRACT 10-Hydroxycamptothecin (HCPT) is an effective anticancer drug against various types of solid tumors . But the antitumor efficacy of HCPT is far from satisfactory because of its poor physicochemical properties, short circulating half-life, low stability, and nonspecific toxicity to normal tissues. Therefore, a targeted delivery strategy for HCPT to pathological sites is eagerly needed to overcome these limitations. The folate-modified N-succinyl-N′-octyl chitosan (folate-SOC) micelle was chosen in this study and served as the targeted delivery system for HCPT to improve the antitumor efficacy. The water-insoluble anticancer drug HCPT was encapsulated into the folate-SOC micelles by the dialysis method. The near- spherical HCPT-loaded folate-SOC (HCPT/folate-SOC) micelles were formed in aqueous media with diameter of about 100-200 nm. The HCPT/folate-SOC micelles displayed a good stability, reasonable drug-loading content (about 10%), and sustained release behavior for the water- insoluble HCPT. Compared with free HCPT, HCPT/folate-SOC micelles exhibited a significant enhancement of cellular uptake, higher cytotoxicity against folate receptor positive tumor cell (Bel-7402), excellent tumor-targeting capability and substantially better antitumor efficacy on the nude mice bearing Bel-7402 xenografts. These results demonstrate the potential of folate- SOC micelles as long-term stable and effective drug delivery systems in cancer therapy.
研究领域:
药学
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癌症研究
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生物医学工程
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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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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DOI
PubMed
高影响因子
DRUG DELIVERY
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2022
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IF 6.819
Dongliang Cheng,Zhiwei Wen,Hui Chen,Shiyuan Lin,Wei Zhang,Xin Tang,Wei Wu
To increase the antitumor drug concentration in the liver tumor site and improve the therapeutic effects, a functionalized liposome (PPP-LIP) with tumor targetability and enhanced internalization after matrix metalloproteinase-2 (MMP2)-triggered cell-penetrating peptide (TATp) exposure was modified with myrcludex B (a synthetic HBV preS-derived lipopeptide endowed with compelling liver tropism) for liver tumor-specific delivery. After intravenous administration, PPP-LIP was mediated by myrcludex B to reach the hepatocyte surface. The MMP2-overexpressing tumor microenvironment deprotected PEG, exposing it to TATp, facilitating tumor penetration and subsequent efficient destruction of tumor cells. In live imaging of small animals and cellular uptake, PPP-LIP was taken up much more than typical unmodified liposomes in the ICR mouse liver and liver tumor cells. Hydroxycamptothecin (HCPT)-loaded PPP-LIP showed a better antitumor effect than commercially available HCPT injections among MTT, three-dimensional (3 D) tumor ball, and tumor-bearing nude mouse experiments. Our findings indicated that PPP-LIP nanocarriers could be a promising tumor-targeted medication delivery strategy for treating liver cancers with elevated MMP2 expression.
研究领域:
药理学
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肿瘤学
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纳米技术
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药物递送系统
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2023
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IF 8
Yuping Zhao,Yanna Zhao,Qisan Ma,Bin Sun,Qingpeng Wang,Zhuang Ding,Huaizhen Zhang,Xiuling Chu,Min Liu,Zhengping Wang,Jun Han
Background The combination of chemo-photodynamic therapy based on nano-technology has emerged as a preferable and promising measure for synergetic antitumor therapy.Purpose The aim of this study was expected to overcome most of the safety concerns from nano-carriers and improve the chemo-photodynamic synergistic antitumor efficacy.Methods Herein, we reported a facile and effective approach based on the self-assembly of chemotherapeutic agent 10-hydroxycamptothecin (HCPT) and photosensitizer chlorin e6 (Ce6) for preparing stably dual-functional nanorods (NRs).Results The chemical thermodynamic parameters obtained from isothermal titration calorimeter (ITC) and the microcosmic configuration snapshots acquired by molecular dynamics (MD) simulations verified that HCPT and Ce6 molecules tended to assemble with each other through various intermolecular forces. The as-prepared HCPT/Ce6 NRs possessed a relatively uniform size of around 165 nm and zeta potential of about −29 mV, together with good stability in aqueous solution and freeze-dried state. In addition, both the extra- and intracellular reactive oxygen species (ROS) generation capacity of the NRs under laser irradiation was significantly enhanced compared with Ce6 injections. Moreover, the dual-functional HCPT/Ce6 NRs exhibited a substantial in vitro/in vivo synergistic antitumor efficacy under laser irradiation due to the integration of the two therapeutic modalities into one drug delivery system. Besides, no obvious hepatic or renal toxicity was observed in the NRs treatment groups.Conclusion Taken together, HCPT/Ce6 NRs demonstrated a powerful efficacy in chemo-photodynamic therapy for breast cancer. Therefore, the carrier-free dual-functional NRs prepared in a facile and effective strategy might give inspiration for the development of combined antitumor therapy.
研究领域:
纳米技术
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药学
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肿瘤学
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材料科学
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DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
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2017
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IF 3.234
Jiannan Li,Weiguo Xu,Jinjin Chen,Di Li,Kai Zhang,Tongjun Liu,Jianxun Ding,Xuesi Chen
Peritoneal adhesion is a complex fibrosis and inflammatory process, and it can be minimized by physical isolation by biomaterial membranes or treatment with cytostatic and/or anti-inflammatory drugs. However, the integration of physical isolation and pharmaceutical therapy in one platform faces many challenges. First, normal polymer antiadhesion membranes are hydrophobic and show low bioadhesion to the injured tissue, which decrease their efficacies. Second, the significantly different release behaviors of various drugs owing to their different hydrophilic/hydrophobic properties limit their synergistic effects. In this study, a highly bioadhesive polymer membrane formed by core–sheath nanofiber to integrate physical isolation and pharmaceutical treatment together for the synergistic prevention of peritoneal adhesion. 10-Hydroxycamptothecin (HCPT) and diclofenac sodium (DS) were loaded in the sheath and core of nanofiber, respectively. The membrane was then treated by ultraviolet-ozone (UVO) for improvement of hydrophilicity and bioadhesion. Owing to the core–sheath structure, the two drugs both performed a sustained release behavior for the cytostatic and anti-inflammatory effects. The in vivo study demonstrated that the UVO-treated and dual-drug-coloaded membrane possessed the best antiadhesion capacity, indicating its potential clinical application.
研究领域:
生物医学工程
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药学
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组织工程
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PubMed
高影响因子
ACS Nano
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2020
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IF 14.588
Ke Li,Chuanchuan Lin,Ye He,Lu Lu,Kun Xu,Bailong Tao,Zengzilu Xia,Rui Zeng,Yulan Mao,Zhong Luo,Kaiyong Cai
As an increased product of high-rate aerobic glycolysis in tumors, lactate could regulate the immunosuppressive tumor microenvironment (TME). A PEG-CDM surface modified, GSH-dependent responsive hollow mesoporous organosilica nanoplatform loaded with hydroxycamptothecin (HCPT) and siMCT-4 was administrated for synergistic tumor chemo-immunotherapy. The nanoplatform cascaded responded to the weak acid TME and the high level of GSH in tumor cells. HCPT and siMCT-4 were continuously released from the nanoplatform for chemotherapy and inhibiting intracellular lactate efflux. The increased intracellular lactate and HCPT effectively induced tumor cell apoptosis. Moreover, the decreased extracellular lactate polarized tumor-associated macrophages (TAMs) phenotype from M2 type to M1 type and restored CD8+ T cell activity in vivo. The results demonstrated that the nanoplatform effectively removed the immunosuppressive TME, inhibited tumor growth, and suppressed lung metastasis of B16F10 cells and 4T1 cells via the combination of inhibiting lactate efflux and chemotherapy. Accordingly, it suggested a strategy to transform immunosuppressive tumors into “hot” tumors and inhibit the tumor growth with high efficiency in vivo.
研究领域:
纳米技术
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肿瘤学
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药学
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免疫治疗
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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
Theranostics
·
2021
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IF 11.556
Wei Qiu,Mengyun Liang,Yuan Gao,Xuelian Yang,Xingyao Zhang,Xiaoli Zhang,Peng Xue,Yuejun Kang,Zhigang Xu
Background: Monotherapy for cancer treatment is limited by unstable efficacy and uncontrollable toxic side effects, while the multifunctional nanoplatform with complex preparation process cannot avoid the potential toxicity of each functional component. Methods: We exploited tumor-specific activated polyamino acid calcified nanoparticles (CHC NPs) as new-type oxidative stress amplification of anticancer drugs via building a safe and biodegradable multifunctional nanoplatform. Giving priority to chemotherapy, and synergizing chemodynamic therapy (CDT) with photodynamic therapy (PDT), this strategy was to achieve enhanced chemotherapy, simultaneously inducing immunogenic cell death and inhibiting tumor cell invasion. Results: Based on amorphous calcium carbonate, pH-responsive nanocarrier was prepared with classical chemotherapeutic drug 10-hydroxycamplothecin (HCPT) and photosensitizer Chlorin e6 (Ce6) to realize multifunctional nanotheranostics. Conclusion: Inventive calcified nanohybrids, where topoisomerase inhibited by HCPT to prevent DNA synthesis, the generation of •OH induced via Fenton reaction, along with a large amount of 1 O 2 produced by Ce6, might be a promising strategy for anti-tumor combination therapy in clinical translation.
研究领域:
纳米技术
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癌症治疗
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药学
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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
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