EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2018
·
IF 4.491
Huaihong Zhang,Yu Sun,Rong Huang,Hui Cang,Zhaosheng Cai,Baiwang Sun
Combination of chemotherapy with photothermal therapy (PTT) demonstrate highly desirable for efficient medical treatment of tumor. At present works, camptothecin (CPT)-containing polymeric prodrug (PCPT) were fabricated by polymerization of a pH-sensitive camptothecin (CPT) prodrug monomer and MPC using reversible addition-fragmentation transfer (RAFT) strategy. The pH-sensitive polymeric prodrug was tethered onto surface of polydopamine (PDA) nanoparticles by amidation chemistry for combination of chemotherapy with photothermal therapy. Specifically, the active CPT quickly released from the multifunctional nanoparticles in acidic microenvironment ascribe to the cleavage of bifunctional silyl ether linkage. Meanwhile, the PDA could convert the near infrared (NIR) light energy into heat with high efficiency, which makes the resulted nanoparticles an effective platform for photothermal therapy. In vitro analysis confirmed that the PDA@PCPT nanoparticles could be efficiently uptaked by HeLa cells and deliver CPT into the nuclei of cancer cells. The cell viability assays indicated an evident in vitro cytotoxicity to HeLa cancer cells under 808 nm light irradiation. Significant tumor regression was also observed in the tumor-bearing mice model with the combinational therapy provided from the PDA@PCPT nanoparticles. The PDA@PCPT multifunctional system which was achieved by a facile route should be a potential candidate in the anti-cancer field due to the synergistic therapeutic effect, which is superior to any single approach.
研究领域:
肿瘤学
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纳米医学
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药物递送
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Research
·
2024
·
IF 9.5
Yu Yuanhao,Zuo Shiyi,Song Jiaxuan,Li Lingxiao,Liu Tian,Guo Jiayu,Li Yaqiao,Wang Danping,Lu Qi,Wang Helin,Zhou Dun,He Zhonggui,Liu Xiaohong,Sun Bingjun,Sun Jin
Albumin nanoparticles (ANPs) offer unique advantages for antitumor drug delivery system, including non-immunogenicity and inherent tumor-targeting capacity. At present, only a few products, such as ABRAXANE® and FYARRO™, have been approved for clinical applications. The poor affinity of doxorubicin (DOX) for albumin, coupled with its numerous severe adverse reactions, poses challenges in the fabrication of desirable albumin nanoparticles loaded with DOX. In this study, we developed prodrugs by conjugating fatty acids of varying lengths with DOX. Our aim was to investigate the balance between efficacy and safety through the selection of appropriate modules. We synthesized five pH-sensitive doxorubicin-fatty acid prodrugs. Compared to free DOX, all DOX prodrug ANPs exhibited a uniform size distribution with desirable sizes of 150 nm. Additionally, DOX prodrugs with hydrazone bonds remained intact in blood circulation while releasing DOX within tumor cells. Significantly, the characteristics of prodrug ANPs were considerably influenced by the length of fatty acids, impacting their in vivo pharmacokinetics, antitumor effectiveness and tumor accumulation. This research offers a detailed understanding of the length of fatty acid influence on DOX-fatty acid prodrug-based ANPs, and it builds a good platform for creating ANPs which prioritize high drug loading, high efficiency, and minimal side effects.
研究领域:
药学
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纳米技术
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癌症研究
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药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
Biomaterials Science
·
2019
·Vol. 7
·期 9
·3652-3661
·
IF 5.251
Yunyan Li,Tong Yan,Wenya Chang,Chongjiang Cao,Dawei Deng
Cancer metastasis is a major cause of high mortality in breast cancer. Despite the progress achieved in nanomaterial-based treatments, the cure rate remains unsatisfactory, owing to their poor biocompatibility and non-specific recognition. Inspired by the cell-mimetic strategy, in this work, we fabricated an intelligent cell-like nano-prodrug (Dox-MPK@MDL) for lung metastasis of breast cancer. Specifically, a DNA tetrahedron dendrimer was selected to act as a rigid internal cytoskeleton, and then sequentially coated with a liposome and macrophage membrane to form cell-like Dox-MPK@MDL via hierarchical self-assembly. Here, it should be noted that pH-sensitive Dox-MPK prodrugs were synthesized and inserted into the DNA-based cytoskeleton (the Dox group is an intercalator of double stranded DNA) in advance for the next anti-metastatic therapy. Our results show that Dox-MPK@MDL specifically targeted the sites of lung metastasis via the biomimetic metastasis-homing effects and intelligently triggered Dox release at the metastatic cancer cells, thereby leading to the significant inhibition of lung metastasis. All these features help to enhance the anti-metastatic therapy efficiency of Dox while maximally reducing side-effects.
研究领域:
纳米技术
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癌症治疗
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生物医学工程
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药物科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2018
·
IF 3.997
Shujuan Xiong,Zhe Wang,Juan Liu,Xiangping Deng,Runde Xiong,Xuan Cao,Zhizhong Xie,Xiaoyong Lei,Yanming Chen,Guotao Tang
This work has presented a novel strategy for designing pH-sensitive TOS-H-DOX prodrug-loaded TPGS nanomicelles for co-delivery TOS and DOX to enhance tumor therapy and reduce the toxic side effects. DOX was covalently conjugated to the vitamin E succinate through hydrazone bond to produce an pH-sensitive prodrug TOS-H-DOX (amido bond as a control, TOS-A-DOX), which was responsive to the acidic environment in tumor cells, and the prodrugs were subsequently encapsulated in the core of TPGS nanomicelles via hydrophobic effects with a significant drug loading capacity. The pH-sensitive prodrug nanomicelles TOS-H-DOX/TPGS exhibited potent release of DOX in acidic media relative to the pH-insensitive prodrug nanomicelles TOS-A-DOX/TPGS, and further studies of their intracellular uptake and intracellular localization demonstrated that TOS-H-DOX/TPGS nanomicelles can be effectively taken up by cells and drugs can be released. In vitro results confirmed that TOS-H-DOX/TPGS nanomicelles exhibited significant antitumor cell proliferation activity compared to TOS-A-DOX/TPGS and free DOX, TPGS. Furthermore, in vivo studies further confirmed an excellent synergistic antitumor efficacy in MCF-7 tumor-bearing nude mice model. More importantly, the H&E staining of the heart, liver, kidney tissue sections of experimental nude mice showed that TOS-H-DOX/TPGS nanomicelles can reduce damage to them.
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2015
·
IF 6.723
Wei-Hai Chen,Qi Lei,Guo-Feng Luo,Hui-Zhen Jia,Sheng Hong,Yu-Xin Liu,Yin-Jia Cheng,Xian-Zheng Zhang
A versatile gold nanoparticle-based multifunctional nanocomposite AuNP@CD-AD-DOX/RGD was constructed flexibly via host–guest interaction for targeted cancer chemotherapy. The pH-sensitive anticancer prodrug AD-Hyd-DOX and the cancer-targeted peptide AD-PEG8-GRGDS were modified on the surface of AuNP@CD simultaneously, which endowed the resultant nanocomposite with the capability to selectively eliminate cancer cells. In vitro studies indicated that the AuNP@CD-AD-DOX/RGD nanocomposite was preferentially uptaken by cancer cells via receptor-mediated endocytosis. Subsequently, anticancer drug DOX was released rapidly upon the intracellular trigger of the acid microenvirenment of endo/lysosomes, inducing apoptosis in cancer cells. As the ideal drug nanocarrier, the multifunctional gold nanoparticles with the active targeting and controllable intracellular release ability hold the great potential in cancer therapy.
研究领域:
纳米技术
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癌症研究
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药物递送系统
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）