International Journal of Nanomedicine
·
2023
·
IF 8
Linjie Yang,Jingyi Hong,Jing Di,Yifei Guo,Meihua Han,Meifeng Liu,Xiangtao Wang
In this study, polyethylene glycol (PEG)ylated 10-hydroxycamptothecin (mPEG1000-HCPT) was synthesized and used as a stabilizer to prepare 10-hydroxycamptothecin (HCPT) nanosuspensions for their in vitro and in vivo antitumor investigation. The resultant HCPT nanosuspensions (HCPT-NSps) had a very high drug payload of 94.90% (w/w) and a mean particle size of 92.90±0.20 nm with narrow size distribution (polydispersity index of 0.16±0.01). HCPT-NSps could be lyophilized without the need of the addition of any cryoprotectant and then be reconstituted into nanosuspensions of a similar size by direct resuspension in water. HCPT was in crystalline form in HCPT-NSps. Using mPEG1000-HCPT as stabilizer, insoluble camptothecin and 7-ethyl-10-hydroxycamptothecin could also be easily made into nanosuspensions with similar features such as high drug payload, small particle size, and cryoprotectant-free freeze drying. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay indicated that the HCPT-NSps had a significantly higher cytotoxicity than HCPT injections, with 3.77 times lower IC50 value against HepG2 cells and 14.1 times lower IC50 value against MCF-7 cells. An in vivo study in H22 tumor-bearing mice after intravenous injection of HCPT-NSps demonstrated that HCPT-NSps significantly improved the antitumor efficacy compared to the commercially available HCPT injections (86.38% vs 34.97%) at the same dose of 5 mg/kg. Even at 1/4 of the dose, HCPT-NSps could also achieve a similar antitumor efficacy to that of HCPT injections. mPEG1000-HCPT may be a highly efficient stabilizer able to provide camptothecin-based drugs, and probably other antitumor agents containing aromatic structure, with unique nanosuspensions or nanocrystals for improved in vivo therapeutic efficacy.
研究领域:
药剂学
·
肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2019
·
IF 3.973
Fangyuan Lv,Dapeng Liu,Hailin Cong,Youqing Shen,Bing Yu
A bottlebrush polymer-cytotoxin prodrug, where a potent anticancer drug 10-hydroxycamptothecin (HCPT) and water-soluble methoxypolyethylene glycols (mPEG) were attached into the polyester backbone, was synthesized via thiol-ene reaction. The synthesized bottlebrush polymer-HCPT conjugate with drug loading content as high as ca. 20.4 wt% was characterized by NMR, IR, UV and fluorescence techniques. The prepared bottlebrush polymer-HCPT prodrug could self-assemble into nanosized micelles ( ca. 153 nm), which were uniform and stable in aqueous solution. Moreover, when exposed to esterase, the formed prodrug micelles as stimuli-responsive nanomaterials could release HCPT. In the cellar uptake and cytotoxicity experiments, the formed prodrug micelles exhibited effective internalization into tumor cells and excellent anticancer efficacies.
研究领域:
生物材料学
·
药学
·
肿瘤学
✓ 已验证
DOI
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2022
·
IF 9.273
Qiongzhe Ren,Xuefeng Tang,Yi Lu,Qing Li,Zhiqian Liao,Shinan Jiang,Haoli Zhang,Zhigang Xu,Lei Luo
The use of nanocrystal technology to manufacture drug delivery systems intended to enhance therapeutic efficacy has attracted the attention of the pharmaceutical industry. However, the clinical application of nanocrystal drugs for injection is restricted by Ostwald ripening and the large-scale use of stabilizers such as polysorbate and lecithin, which have potential toxicity risks including hemolysis and allergies. Here, we designed an amorphous nanocrystal drug complex (IHNC), which is stabilizer-free and composed of indocyanine green (ICG) framework loading with a chemotherapeutic agent of 10-hydroxycamptothecin (HCPT). Considering the possibility of industrial manufacturing, IHNC was simply prepared with the assistance of ferric ion (III) via supramolecular assembly strategy. The theoretical result of Materials Studio simulation indicated that the prepared ICG-Fe(III) framework showed a stable spherical structure with the appropriate cavity for encapsulating the two drugs of HCPT and ICG with equal mass ratio. The IHNC was stable at physiological pH, with excellent PTT/PDT efficacy, and in vivo probing characteristics. The nanoscale size and reductive stimuli-responsiveness can be conducive to drug accumulation into the tumor site and rapid unloading of cargo. Moreover, such combination therapy showed synergistic photo/chemotherapy effect against 4T1 breast cancer and its tumor inhibition rate even up to 79.4%. These findings demonstrated that the nanocrystal drug delivery strategy could avoid the use of stabilizers and provide a new strategy for drug delivery for combination therapy.
研究领域:
药学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2022
·
IF 7.033
Yue Shang,Hui Zhang,Yajia Cheng,Peipei Cao,Jianlin Cui,Xuebo Yin,Saijun Fan,Yuhao Li
Background Hepatocellular carcinoma (HCC), arising from hepatocytes, is the most common primary liver cancer. It is urgent to develop novel therapeutic approaches to improve the grim prognosis of advanced HCC. 10-hydroxycamptothecin (HCPT) has good antitumor activity in cells; however, its hydrophobicity limits its application in the chemotherapy of HCC. Recently, nanoscale porphyrin metal-organic frameworks have been used as drug carriers due to their low biotoxicity and photodynamic properties.Methods Nanoscale zirconium porphyrin metal-organic frameworks (NMOFs) were coated with arginine-glycine-aspartic acid (RGD) peptide to prepare NMOFs-RGD first. The HepG2 cell line, zebrafish embryos and larvae were used to test the biotoxicity and fluorescence imaging capability of NMOFs-RGD both in vitro and in vivo. Then, NMOFs were used as the skeleton, HCPT was assembled into the pores of NMOFs, while RGD peptide was wrapped around to synthesize a novel kind of nanocomposites, HCPT@NMOFs-RGD. The tissue distribution and chemo- and photodynamic therapeutic effects of HCPT@NMOFs-RGD were evaluated in a doxycycline-induced zebrafish HCC model and xenograft mouse model.Results NMOFs-RGD had low biotoxicity, good biocompatibility and excellent imaging capability. In HCC-bearing zebrafish, HCPT@NMOFs-RGD were specifically enriched in the tumor by binding specifically to integrin αvβ3 and led to a reduction in tumor volume. Moreover, the xenografts in mice were eliminated remarkably following HCPT@NMOFs-RGD treatment with laser irradiation, while little morphological change was found in other main organs.Conclusion The nanocomposites HCPT@NMOFs-RGD accomplish tumor targeting and play synergistic chemo- and photodynamic therapeutic effects on HCC, offering a novel imaging-guided drug delivery and theranostic platform.
研究领域:
肿瘤学
·
药学
·
生物医学工程
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Research
·
2024
·
IF 9.5
Zhang Hanming,Gao Honglin,Zhang Yicong,Han Yikun,Lin Qing,Gong Tao,Sun Xun,Zhang Zhirong,Zhang Ling,Huang Shiqi
Unique physiopathological characteristics of tumor tissues impose obstacles to the sufficient penetration of traditional nanomedicines, resulting in undesirable drug delivery efficacy and therapeutic outcomes. Here, we constructed TRAIL-[ND-HCPT] GAC , a synergistic hydroxycamptothecin (HCPT) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein co-loaded disk-shaped nanocarrier with γ -glutamyl transpeptidase responsiveness. When the novel nanodisks extravasated into the tumor interstitium, the γ -glutamyl transpeptidase overexpressed on the tumor cell membranes cleaved the γ -glutamyl portions of the nanodisk surface to produce positively charged amino groups. As a result, the cationic nanodisks possessed stronger tumor infiltration ability through transcytosis than anionic nanodisks. HCPT and TRAIL exerted synergistic antitumor effects with better overall therapeutic efficacy. This TRAIL-[ND-HCPT] GAC system performed significantly better than free HCPT and remarkably prolonged the survival of breast tumor-bearing mice with no significant toxicity.
研究领域:
药学
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2024
·
IF 2.7
Fangling Cao,Jing Xu,Xiujie Wang,Yuanyuan Liu,Shuqin Pang,Qishu Jiao,Shuyao Zhou,Wenying Zhong,Keming Xu
Self-assembled peptide hydrogels possess remarkable biological activity and biocompatibility. When utilized for local drug delivery, they require enhanced mechanical properties and the ability to facilitate controlled release of drugs. Herein, we present the design and synthesis of a supramolecular hydrogel (Fmoc-GFFG/SBE-β-CD). The hydrogel incorporates host–guest interactions between a self-assembling peptide (Fmoc-GFFG) and cyclodextrin molecules (SBE-β-CD) to improve the viscoelastic strength of the hydrogel while maintaining biocompatibility. With remarkable shear-thinning properties, the Fmoc-GFFG/SBE-β-CD hydrogel exhibits enhanced in vivo retention time, thereby facilitating the development of an injectable drug delivery system. Using 10-hydroxycamptothecin (HCPT) as a model drug, we develop a hydrogel system (Fmoc-GFFG/SBE-β-CD@HCPT) that capitalizes on the inclusion complex formation between SBE-β-CD and HCPT. The resulting composite hydrogels effectively prevent the agglomeration of drug molecules, ensuring the sustained release of HCPT while preserving its anticancer efficacy. The findings presented in this work establish a foundation for the broadening of peptide-based biomaterials and offer a promising avenue for the development of sophisticated drug delivery systems.
研究领域:
生物材料
·
药剂学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
FERROELECTRICS
·
2021
·
IF 0.62
Feng Wang,Fang-Yuan Lv,Kui-Long Liu,Zhi-Hao Li,Shu Niu,Yun-Yi Zhang,Hai-Lin Cong,You-Qing Shen,Bing Yu
A MoS2 nanosheets drug delivery system with photothermal conversion ability was synthesized. The drug loading content of the synthesized was as high as 24.5%. The drug HCPT was modified by lipoic acid (LA) and connected onto MoS2 nanosheets through S-Mo bond, which is more stable than physical adsorption. Due to the ester bond between HCPT and MoS2 nanosheets, the drug delivery system could responsively release HCPT when exposed to esterase.
研究领域:
材料科学与工程
·
生物医学工程
·
药剂学
✓ 已验证
产品关联
DOI
高影响因子
Nanomaterials
·
2021
·Vol. 11
·期 11
·2854
·
IF 5.076
Yuqiong Shi,Wei Liu,Xiangrong Wu,Jinhua Zhu,Danyang Zhou,Xiuhua Liu
The poor water solubility and severe side effects of hydroxycamptothecin (HCPT) limit its clinical application; therefore, it is necessary to synthesize applicable nanodrug carriers with good solubility to expand the applications of HCPT. In this study, a hydrophilic metal–organic framework (MOF) with amphoteric carboxylic acid ligands as linkers was first synthesized and characterized. Then, water-soluble acrylamide and methacrylic acid were applied as monomers to prepare a water-soluble polyacid polymer MOF@P, which had a solubility of 370 μg/mL. The effects of the MOF@P material on the HCPT loading and solubility were investigated. The results showed that the polymer material could improve the HCPT solubility in water. Moreover, the in vitro release study indicated that the MOF@P polymeric composite exhibited a sustained-release effect on HCPT, with a cumulative release rate of 30.18% in 72 h at pH 7.4. Furthermore, the cytotoxicity test demonstrated that the hydrophilic MOF and the MOF@P had low cell toxicities. The results indicate that the prepared MOF@P polymeric complex can be applied for the sustained release of HCPT in clinics.Keywords:polyacid polymer;metal organic frameworks;HCPT delivery
研究领域:
药学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 23
·7703
·
IF 4.6
Hongda Cheng
Metal–organic frameworks (MOFs) are considered to be promising materials for drug delivery. In this work, a Zinc-based MOF nanocomposite IRMOF-3 was introduced as a drug carrier for 10-hydroxycamptothecine (HCPT). Without an extra drug-loading process, a nanoscale drug delivery material HCPT@IRMOF-3 was prepared via one-pot synthesis. The composition and structure of the material were investigated, and the drug release character was measured. Compared with preparing IRMOF-3 first and loading the drug, the one-pot-prepared HCPT@IRMOF-3 exhibited a higher drug-loading capacity. The material presented pH-responsive release. The HCPT release rate at pH 5.0 was significantly higher than that at pH 7.4. The cytotoxicity experiments showed that IRMOF-3 was non-toxic, and HCPT@IRMOF-3 exhibited notable cytotoxicity to Hela and SH-SY5Y cells. One-pot synthesis is a simple and rapid method for the preparation of an MOF drug delivery system, and IRMOF-3 can be potentially used in pH-responsive drug delivery systems.Keywords:IRMOF-3;drug delivery;one pot;pH response;HCPT
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2017
·
IF 4.3
Yang Liu,Dan Li,Xinhong Guo,Haiwei Xu,Zhi Li,Yanling Zhang,Chuanjun Song,Ruhan Fan,Xing Tang,Zhenzhong Zhang
We synthesized a pH-responsive conjugate of 10-hydroxycamptothecin-thiosemicarbazide-linear polyethylene glycol 2000 (PEG2000). The conjugate was confirmed by matrix-assisted laser desorption time of flight mass spectrometry, 1 H NMR, and 13 C NMR. The water solubility of the prodrug was increased by over 3,000 times; much longer body circulation time, higher tumor-targeting ability, and reduced toxicity were observed, compared with commercial 10-HCPT injection. The linker contains a pH-sensitive hydrazone bond, which breaks under low pH conditions in the tumor microenvironment. The conjugates showed good stability in phosphate-buffered saline (pH 7.4) and rat plasma. This amphiphilic conjugate could self-assemble into nanosized micelles of 80–100 nm. Cytotoxicity assay results indicate significantly higher efficacy of the conjugate (IC 50 [half maximal inhibitory concentration] =0.117 µM on SW180 cells) than 10-HCPT solution (IC 50 =0.241 µM on SW480 cells). Cellular uptake analysis suggested its rapid internalization and nuclear transport. Pharmacokinetic analysis of the conjugates demonstrated that the conjugate circulated for a longer time in the blood circulation system ( T 2/1 =10.516±1.158 h) than did 10-HCPT solution ( T 2/1 =1.859±1.385 h), and that it also enhanced the targeting and mean residence time (MRT 0–inf =39.873±4.549 h) in the tumor site, compared with 10-HCPT (MRT 0–inf =9.247±1.026 h). Finally, the conjugate demonstrated an increased tumor growth inhibition effect (TIR =82.66%±7.175%) in vivo and lower side effects than 10-HCPT (TIR =63.85%±5.233%). This prodrug holds great promise in improving therapeutic efficacy and overcoming multidrug resistance.
研究领域:
药学
·
药物递送系统
·
癌症治疗
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2017
·
IF 0
Yang Liu,Juan Li,Zhi Li,Xing Tang,Zhenzhong Zhang
A pH-responsive conjugate based 10-hydroxycamptothecin-thiosemicarbazide-polyethene glycol 2000 (10-HCPT-hydro-PEG) nano-micelles were prepared in our previous study. In the present study, ultra-performance liquid chromatography (UPLC-MS) method is developed to investigate its pharmacokinetics and biodistribution in tumor bearing mice. The results demonstrated that the conjugate circulated for a much longer time in the blood circulation system than commercial 10-HCPT injection, and bioavailability was significantly improved compared with 10-HCPT. In vivo biodistribution study showed that the conjugate could enhance the targeting and residence time in tumor site.
研究领域:
药学
·
纳米技术
·
癌症研究
✓ 已验证
DOI
PubMed
Journal of Inorganic and Organometallic Polymers and Materials
·
2022
·Vol. 32
·期 8
·2986-2993
·
IF 3.518
Hao Bei-bei,Deng Xiu-zhen,Yang Jia-ke,Jia Ying-dong,Shang Xiao-jun,Shi Yong-li,Yan Xi-qing
A novel folate-decorated and magnetic mediated drug delivery system was fabricated by combining folate and magnetic nanoparticles to the surface of silica mesoporous nanoparticles (FMMSNs) via chemical reaction. The 10-hydroxycamptothecin (10-HPCT), an analogue of camptothecin, was sealed in the mesoporous to evaluate the system’s pharmaceutics performance. The diameter of the FMMSMs was about 100 nm and the in vitro release result showed that the applied magnetic field could influence the release process. The result of the inhibition rate of the 10-HPCT loaded FMMSNs to HepG-2 cells revealed that they could be influenced by the applied magnetic field or the folic acid bonded on the surface of the mesoporous nanoparticles.
研究领域:
药剂学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）