JOURNAL OF NANOBIOTECHNOLOGY
·
2018
·Vol. 16
·期 1
·1-15
·
IF 5.294
Li Yuanyuan,Shi Sanjun,Ming Yue,Wang Linli,Li Chenwen,Luo Minghe,Li Ziwei,Li Bin,Chen Jianhong
Background Cancer stem cells (CSCs) are highly proliferative and tumorigenic, which contributes to chemotherapy resistance and tumor occurrence. CSCs specific therapy may achieve excellent therapeutic effects, especially to the drug-resistant tumors. Results In this study, we developed a kind of targeting nanoparticle system based on cationic albumin functionalized with hyaluronic acid (HA) to target the CD44 overexpressed CSCs. All-trans-retinoic acid (ATRA) was encapsulated in the nanoparticles with ultrahigh encapsulation efficiency (EE%) of 93% and loading content of 8.37%. TEM analysis showed the nanoparticles were spherical, uniform-sized and surrounded by a coating layer consists of HA. Four weeks of continuously measurements of size, PDI and EE% revealed the high stability of nanoparticles. Thanks to HA conjugation on the surface, the resultant nanoparticles (HA-eNPs) demonstrated high affinity and specific binding to CD44-enriched B16F10 cells. In vivo imaging revealed that HA-eNPs can targeted accumulate in tumor-bearing lung of mouse. The cytotoxicity tests illustrated that ATRA-laden HA-eNPs possessed better killing ability to B16F10 cells than free drug or normal nanoparticles in the same dose, indicating its good targeting property. Moreover, HA-eNPs/ATRA treatment decreased side population of B16F10 cells significantly in vitro. Finally, tumor growth was significantly inhibited by HA-eNPs/ATRA in lung metastasis tumor mice. Conclusions These results demonstrate that the HA functionalized albumin nanoparticles is an efficient system for targeted delivery of antitumor drugs to eliminate the CSCs.
研究领域:
肿瘤学
·
纳米技术
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Lifeng Luo,Baoli Zhang,Feng Tao,Zhong Chen,Qingsong Ye,Xiaozhi Zhao,Jinhui Wu
Tumor metastasis contributes to the low overall survival of tumor patients, while transforming growth factor-β (TGFβ) has been recognized as a prominently promoting factor in the development of tumor metastasis. Platelets reserve abundant TGFβ, which will be secreted to peripheral blood after activation, and they are the dominant source of circulating TGFβ. Therefore, downregulation of platelet-derived TGFβ is expected to inhibit the metastasis of circulating tumor cells. Here, unfolded human serum albumin (HSA)-coated perfluorotributylamine (PFTBA) nanoparticles were constructed to display a favorable platelet delivery and an antiplatelet effect to downregulate platelet-derived TGFβ in vitro and in blood plasma. PFTBA@HSA-mediated TGFβ downregulation impaired epithelial-mesenchymal transition of tumor cells as well as their migration and invasion behaviors and enhanced immune surveillance of NK cells. Intravenous injection of PFTBA@HSA effectively reduced tumor metastasis on the lungs or liver to improve the survival rate of mice on multiple metastatic models, including CT26 colon cancer, B16F10 melanoma, and 4T1 breast cancer. Compared with the clinical antiplatelet drug ticagrelor, PFTBA@HSA reduced bleeding risk when displaying a favorable downregulation on platelet-derived TGFβ, thereby obtaining a higher therapy benefit. Together, this study confirmed that downregulation of platelet-derived TGFβ by PFTBA@HSA will be a potential approach and therapeutic candidate for the prevention of tumor metastasis.
研究领域:
肿瘤学
·
药理学
·
纳米技术
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Lanlan Fan,Panyu Du,Yaru Li,Xuefei Chen,Fang Liu,Yuning Liu,Alexey M. Petrov,Xin Li,Zheng Wang,Yanjun Zhao
Ferroptotic cancer therapy has been extensively investigated since the genesis of the ferroptosis concept. However, the therapeutic efficacy of ferroptosis induction in heterogeneous and plastic melanoma has been compromised, because the melanocytic and transitory cell subpopulation is resistant to iron-dependent oxidative stress. Here, we report a phenotype-altering liposomal nanomedicine to enable the ferroptosis-resistant subtypes of melanoma cells vulnerable to lipid peroxidation via senescence induction. The strategy involves the ratiometric coencapsulation of a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor (palbociclib) and a ferroptosis inducer (auranofin) within cRGD peptide-modified targeted liposomes. The two drugs showed a synergistic anticancer effect in the model B16F10 melanoma cells, as evidenced by the combination index analysis (<1). The liposomes could efficiently deliver both drugs into B16F10 cells in a targeted manner. Afterward, the liposomes potently induced the intracellular redox imbalance and lipid peroxidation. Palbociclib significantly provoked cell cycle arrest at the G0/G1 phase, which sensitized auranofin-caused ferroptosis through senescence induction. Meanwhile, palbociclib depleted intracellular glutathione (GSH) and reduced nicotinamide adenine dinucleotide phosphate (NADPH), further boosting ferroptosis. The proof-of-concept was also demonstrated in the B16F10 tumor-bearing mice model. The current work offers a promising ferroptosis-targeting strategy for effectively treating heterogeneous melanoma by manipulating the cellular plasticity.
研究领域:
癌症治疗
·
药学
·
纳米技术
·
肿瘤学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2018
·Vol. 14
·期 3
·477-495
·
IF 5.068
Sang Mangmang,Zhang Zhongtao,Liu Fulei,Hu Lejian,Li Lingchao,Chen Li,Feng Feng,Liu Wenyuan,Qu Wei
A novel multifunctional hyaluronic acid-decorated redox-responsive magnetic complex micelle (HA/CSO-SS-Hex/Fe3O4/PTX) based on a reducible hexadecanol-modified chitosan oligosaccharide polymer micelle (CSO-SS-Hex) coated with hyaluronic acid (HA) and loaded with
paclitaxel (PTX) Fe3O4 nanoparticles is developed. HA is coated onto the surface of micelles via electrostatic absorption and acts as a targeting ligand for CD44 over expression in many tumor cells. A CSO-SS-Hex polymer micelle was used for PTX incorporation and GSH-triggered
intracellular release. The PTX in micelles was used to provide chemotherapy. Fe3O4 nanoparticles were used for magnetic targeting. The complex micelle showed enhanced antitumor efficiency and anti-cell-migration activity. The HA/CSO-SS-Hex/Fe3O4/PTX
micelle was stable under physiological conditions, while it was sensitive to release the loaded drug in the presence of 10 mM glutathione (GSH). The complex micelle showed enhanced cellular uptake and fast drug release due to the combined effect of magnet targeting, CD44 receptor-mediated
internalization and redox-response drug release in tumor cells. Cell viability tests revealed that HA/CSO-SS-Hex/Fe3O4/PTX micelle displayed enhanced cytotoxicity against A549, B16F10 and HepG2 cell lines compared to non-targeted formulations of PTX. An anti-cell migration
assay was also performed. The result showed that although there was no significant difference in the anti-cell migration activities between the HA/CSO-SS-Hex/Fe3O4/PTX micelle and free PTX, the activities of HA/CSO-SS-Hex/Fe3O4/PTX were stronger
than non-targeted CSO-SS-Hex/Fe3O4/PTX micelles. Thus, the novel HA/CSO-SS-Hex/Fe3O4/PTX micelle is highly effective for targeted drug delivery and might have potential implications for the chemotherapy of primary tumors and their metastases.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2024
·
IF 5.3
Sifang Zhao,Fengjiao Chen,Xianwu Chen,Hongze Liang,Hui Tan,Lingling Zhao
The tumor microenvironment is characterized by several hallmarks such as an acidic pH and high glucose levels in tumor tissues and increased expression of specific proteins and/or sugars on the surface of tumor cells. These unique hallmarks of tumors can be considered in the design of multifunctional drug delivery nanosystems to improve the efficiency of tumor therapy through targeted drug delivery and specific drug release in the tumor tissue. In this study, phenylboronic acid-modified pH- and glucose-responsive polymer micelles were designed for the targeted delivery of anticancer drugs. The polymeric micelles demonstrated prolonged and pH/glucose-triggered drug release and enhanced cellular internalization by B16F10 cells through a receptor-mediated endocytosis pathway. The polymeric micellar system could inhibit the proliferation of B16F10 cells with IC50 values lower than those of unmodified micelles. In addition, the polymeric micellar system could markedly suppress cell migration, colony formation, and invasion and promote the apoptosis of B16F10 cells, indicating good anticancer efficiency in vitro. Therefore, this polymeric nanocarrier provides a potential platform for targeted anticancer therapy.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
Journal of Biomedical Nanotechnology
·
2019
·Vol. 15
·期 7
·1482-1491
·
IF 0
Wang Xu,Liang Gao-Feng,Hao Xue-Qin,Feng Shu-Ying,Dai Lu,An Jun-Ling,Li Jing-Hua,Shi Hao,Feng Wen-Po,Zhang Xin
As a widely used first-line chemotherapy drug for tumor, Doxorubicin (DOX) can induce various side effects on normal tissues because of its non-specific distribution in the body. Emerging evidence has shown that platelets have the capability to recognize and interact with tumor cells.
Inspired by this, the platelet-based drug delivery system was constructed by loading of DOX in platelet cytoplasm and modification of transferrin on the surface of platelet (Tf-P-DOX). The encapsulation efficiency of DOX in platelet was the highest at the DOX concentration of 0.05 mM, and
reached to 64.9%. Fluorescence microscopy showed that the Tf-P-DOX facilitated cell uptakes and enhanced intracellular drug accumulation in B16F10 cells. Compared with free DOX, Tf-P-DOX exhibited an enhanced effect on cell apoptosis at the same concentration of DOX. In vivo imaging
system showed that the near-infrared fluorescence of B16F10 tumor-bearing mice was mainly accumulated in the tumor site, which caused the inhibition of tumor growth in mice. The morphological changes of tumor tissue in Tf-P-DOX group was significant in comparison with those of the control
group, including the small nucleus, the insufficiency of cancerous nest, and the infiltration of inflammatory cells, while Tf-P-DOX did not show significant adverse effects on normal tissues. Compared with the control group, the levels of caspase 9 and caspase 3 protein expressions were increased
significantly in Tf-P-DOX group. Our studies suggest platelets can be repurposed as promising carriers for efficient targeting and treatment of solid tumors.
研究领域:
药理学
·
肿瘤学
·
药物递送系统
·
生物医学工程
✓ 已验证
DOI
PubMed
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Xidong Tian,Hriday Bera,Xiong Guo,Ruizhao Xu,Jin Sun,Zhonggui He,Dongmei Cun,Mingshi Yang
Chemotherapeutics often failed to elicit optimal antitumor responses against lung cancer due to their limited exposure and accumulation in tumors. To achieve an effective therapeutic outcome of paclitaxel (PTX) against metastatic lung cancer with attenuated systemic and local toxicities, pulmonary delivery of redox-responsive PTX dimeric nanoparticles (NPs) was introduced. PTX dimers conjugated through variable lengths of diacid linkers containing disulfide bonds (−SS−) (i.e., α–PTX–SS–PTX, β–PTX–SS–PTX, and γ–PTX–SS–PTX) were initially synthesized and were subsequently self-assembled into uniform nanosized particles in the presence of vitamin E TPGS with high drug loading capacity (DE > 97%). Among various redox-sensitive scaffolds, β–PTX–SS–PTX NPs exhibited an optimal reactive oxygen species/glutathione-responsive drug release behavior, causing a lower local toxicity profile of PTX in the lungs. The scaffolds also demonstrated excellent colloidal stability, cellular uptake efficiency, and discriminating cytotoxicity between cancer and healthy cells. Further, they depicted an improved lung retention as compared to the control nanovesicles (β–PTX–CC–PTX) devoid of the redox-sensitive disulfide motif. In the B16F10 melanoma metastatic lung cancer mouse model, intratracheally delivered β–PTX–SS–PTX NPs exhibited a stronger anticancer potential with reduced systemic toxicity as compared to Taxol intravenous injection containing an equivalent PTX dose. The PTX dimeric NPs could also dramatically reduce the local toxicity relative to Taxol following their pulmonary delivery. Thus, this study presents redox-responsive PTX dimeric NPs as a promising nanomedicine for improved therapeutic efficacy against metastatic lung cancer.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Huapan Fang,Linfu Chen,Zheng Deng,Yunxuan Gao,Yang Yang,Qian Chen,Zhuang Liu
Oral administration of protein drugs has always been challenging owing to various intestinal barriers. Herein, we developed an efficient oral protein delivery strategy by using in situ polymerization of zwitterions to encapsulate proteins, which were then loaded into enteric coated capsules for oral feeding. After oral administration of such capsules, the enteric coating would be degraded once the capsule enters the intestine, releasing polyzwitterion/protein nanocomplexes. With the help of polyzwitterion modification, such nanocomplexes were able to pass through the mucus and cellular barriers, likely by the proton-assisted amino acid transporter 1 (PAT1) pathway. Such a polyzwitterion-based protein encapsulation strategy could allow for effective oral delivery of different proteins, including bovine serum albumin (BSA), insulin, and antibodies. Using this strategy, the oral bioavailabilities of insulin and immunoglobin G (IgG) were measured to be as high as 16.9% and 12.5%, respectively. Notably, oral feeding of polyzwitterion/insulin capsules could effectively lower the blood glucose level of diabetic animals (mice, rats, and pigs). Moreover, polyzwitterion/antiprogramed death-1 (αPD-1) capsules were able to induce efficient antitumor immune responses, showing significant tumor inhibition effects toward B16F10- and 4T1-tumor bearing mouse models after oral administration. No significant toxic effect was observed for such oral protein formulations in the treated animals. Our work presents a strategy for the efficient oral delivery of protein drugs, including those with large molecular weights (e.g., antibodies) that can hardly be orally delivered using existing technologies.
研究领域:
药学
·
生物技术
·
药物递送系统
·
蛋白质工程
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Jiangping Huang,Meiting Li,Chengyun Han,Zhongwei Zhang,Xiang Liu,Zhixuan Ying,Peipei Yin,Lingguang Yang
Acer truncatum is a multifunctional tree species with broad applications in ornamental, healthy drink, and seed oil. In the present study, proanthocyanidins were isolated from the seed coats of A. truncatum , which were largely discarded as industrial wastes in seed oil production. Meanwhile, structural features, effects and mechanisms of anti-tyrosinase, anti-melanogenesis, and anti-browning of A. truncatum seed coat proanthocyanidins (ASPs) were systematically investigated. The joint application of FT-IR, MALDI-TOF-MS, hiolysis-coupled reverse-phase LC-ESI-MS, together with normal-phase LC confirmed that ASPs were predominately constituted by procyanidins with a mean polymerization degree of 12.09. Furthermore, ASPs powerfully inhibited both monophenolase and diphenolase activities of tyrosinase, and the inhibition of diphenolase was proved to be reversible and competitive−uncompetitive mixed type. Analyses of fluorescence quenching, UV spectra, and copper-ion chelation indicated that ASPs could inhibit tyrosinase in varied stages, and molecular docking and dynamic simulation further revealed the interaction mode between ASPs and tyrosinase. Cell assays further suggested that ASPs exhibited a strong inhibition against intracellular tyrosinase activity and melanin production through suppressing the expression of tyrosinase and microphthalmia transcription factor (MITF) at transcription level and caused apoptosis in B16F10 cells at higher concentrations. Antioxidant and anti-browning studies demonstrated that ASPs possessed high capacities of antioxidant, and potently suppress the browning of fresh-cut potatoes. Therefore, this study confirmed that seed coats of Acer truncatum is a potential natural source of tyrosinase, melanogenesis, and browning inhibitor, which provided a theoretical basis for the utilization of ASPs in the cosmetics, pharmaceutical, and food industries.
研究领域:
药理学
·
生物化学
·
化妆品科学
·
食品科学
·
植物科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2021
·Vol. 21
·期 6
·2100049
·
IF 4.979
Yingge Shi,Dong Li,Chaoliang He,Xuesi Chen
Combination therapy can be used to enhance the therapeutic response and decrease side effects during cancer treatment. In this study, a system is developed to locally deliver the immune checkpoint blockade antibody targeting programmed death-ligand 1 (anti-PD-L1 or aPD-L1) and doxorubicin (Dox), by an injectable, biocompatible polypeptide hydrogel as a drug depot. The localized and sustained release of Dox after the intratumoral injection of the co-loaded hydrogel induces immunogenic tumor cell death, thus promoting an antitumor immunological response. The tumor inhibitory effect is significantly enhanced by the simultaneous release of aPD-L1 at the tumor site thanks to its action on the inhibition of the PD-1/PD-L1 pathway and restoration of the tumor-killing effect of cytotoxic T cells. Treatment of the B16F10 melanoma model with the aPD-L1 and Dox co-loaded hydrogel leads to a remarkable inhibition of tumor progression and prolongation of animal survival.
研究领域:
肿瘤学
·
药学
·
免疫疗法
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2020
·
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
·
肿瘤学
·
药学
·
免疫治疗
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Huiwen Hou,Yan Li,Wen Tang,Didi Gao,Zengmei Liu,Feiyan Zhao,Xinqing Gao,Peixue Ling,Fengshan Wang,Feng Sun,Haining Tan
Blocking the tumor nutrient supply through angiogenic inhibitors is an effective treatment approach for malignant tumors. However, using angiogenic inhibitors alone may not be enough to achieve a significant tumor response. Therefore, we recently designed a universal drug delivery system combining chemotherapy and anti-angiogenic therapy to target tumor cells while minimizing drug-related side effects. This system (termed as PCCE) is composed of biomaterial chondroitin sulfate (CS), the anti-angiogenic peptide ES2, and paclitaxel (PTX), which collectively enhance antitumor properties. Interestingly, the PCCE system is conferred exceptional cell membrane permeability due to inherent characteristics of CS, including CD44 receptor-mediated endocytosis. The PCCE could respond to the acidic and high glutathione conditions, thereby releasing PTX and ES2. PCCE could effectively inhibit the proliferation, migration, and invasion of tumor cells and cause apoptosis, while PCCE can affect the endothelial cells tube formation and exert anti-angiogenic function. Consistently, more potent in vivo antitumor efficacy and non-toxic sides were demonstrated in B16F10 xenograft mouse models. PCCE can achieve excellent antitumor activity via modulating angiogenic and apoptosis-related factors. In summary, we have successfully developed an intelligent and responsive CS-based nanocarrier known as PCCE for delivering various antitumor drugs, offering a promising strategy for treating malignant tumors.
研究领域:
药理学
·
纳米技术
·
肿瘤学
·
药物递送系统
✓ 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）