International Journal of Nanomedicine
·
2023
·
IF 8
Lian Deng,Xiongjie Zhu,Zhongjian Yu,Ying Li,Lingyu Qin,Zhile Liu,Longbao Feng,Rui Guo,Yanfang Zheng
Background Although single-drug chemotherapy is still an effective treatment for esophageal cancer, its long-term application is limited by severe side-effects, poor bioavailability, and drug-resistance. Increasing attention has been paid to nanomedicines because of their good biological safety, targeting capabilities, and high-efficiency loading of multiple drugs. Herein, we have developed a novel T7 peptide-modified pH-responsive targeting nanosystem co-loaded with docetaxel and curcumin for the treatment of esophageal cancer.Methods Firstly, CM-β-CD-PEI-PEG-T7/DTX/CUR (T7-NP-DC) was synthesized by the double emulsion (W/O/W) method. The targeting capacity of the nanocarrier was then investigated by in vitro and in vivo assays using targeted (T7-NP) and non-targeted nanoparticles (NP). Furthermore, the anti-tumor efficacy of T7-NP-DC was studied using esophageal cancer cells (KYSE150 and KYSE510) and a KYSE150 xenograft tumor model.Results T7-NP-DC was synthesized successfully and its diameter was determined to be about 100 nm by transmission electron microscopy and dynamic light scattering. T7-NP-DC with docetaxel and curcumin loading of 10% and 6.1%, respectively, had good colloidal stability and exhibited pH-responsive drug release. Good biosafety was observed, even when the concentration was as high as 800 μg/mL. Significant enhancement of T7-NP uptake was observed 6 hours after intravenous injection compared with NP. In addition, the therapeutic efficacy of T7-NP-DC was better than NP-DC and docetaxel in terms of growth suppression in the KYSE150 esophageal cancer model.Conclusion The findings demonstrated that T7-NP-DC is a promising, non-toxic, and controllable nanoparticle that is capable of simultaneous delivery of the chemotherapy drug, docetaxel, and the Chinese Medicine, curcumin, for treatment of esophageal cancer. This novel T7-modified targeting nanosystem releases loaded drugs when exposed to the acidic microenvironment of the tumor and exerts a synergistic anti-tumor effect. The data indicate that the nanomaterials can safely exert synergistic anti-tumor effects and provide an excellent therapeutic platform for combination therapy of esophageal cancer.
研究领域:
纳米医学
·
肿瘤学
·
药学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL SCIENCES
·
2021
·
IF 3.534
Hong Wang,Wanghao Chen,Guojian Wu,Jun Kong,Shaofei Yuan,Lukui Chen
Glioma-targeted drug delivery is a hugely challenging task because of the multibarrier in the brain. In this study, we report a magnetic T7 peptide&AS1411 aptamer-modified microemulsion for triple glioma-targeted delivery of shikonin and docetaxel (Fe 3 O 4 @T7/AS1411/DTX&SKN-M). Such a system comprises two tumor-targeted ligands (T7 peptide and AS1411 aptamer), ultra-small superparamagnetic iron oxide nanoparticle (Fe 3 O 4 ), and shikonin&docetaxel-coloaded microemulsion (SKN&DTX-M). Fe 3 O 4 @T7/AS1411/DTX&SKN-M is capable of stably circulating in the blood, accumulating around the brain under an external magnetic field, distributing inside the glioma via the affinity to nucleolin/transferrin receptor, and retarding the growth of orthotopic glioma. Fe 3 O 4 @T7/AS1411/DTX&SKN-M encapsulated Fe 3 O 4 nanoparticles in the core to obtain the superparamagnetism, which did not influence the main surface properties. Introducing 6% (wt%) of DSPE-PEG 2000 -T7 and 180 nM of AS1411 collaboratively enhanced the murine glioma (G422) cellular uptake of Fe 3 O 4 @T7/AS1411/DTX&SKN-M and thereby achieved the strongest antiproliferation among all the groups. Notably, the drug distribution at the brain sites of orthotopic Luc-G422 glioma tumor-bearing nude mice treated with Fe 3 O 4 @T7/AS1411/DTX&SKN-M was overwhelming among all the treatments. Most importantly, Fe 3 O 4 @T7/AS1411/DTX&SKN-M not only significantly reduced the luminescence signal at the brain areas of orthotopic Luc-G422 glioma mice but also prolonged the overall survival period. The enhancement of anti-glioma efficacy was associated with down-regulating the population of CD133- and CD44-positive cells within the tumors. In summary, such a triple glioma-targeted delivery of shikonin and docetaxel using combinational magnetism and T7/AS1411 modification strategies provides a promising method for synergistic and precise glioma therapy.
研究领域:
药学
·
肿瘤学
·
纳米医学
✓ 已验证
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Yun Deng,Wangxiang Yan,Dalong Shu,Li Zhu,Songling Chen,Yu Chen
Oral squamous cell carcinoma (OSCC) is a common oral malignancy. However, conventional chemotherapeutic strategies present many limitations. To overcome these challenges, a cell membrane-camouflaged amphiphilic self-delivery nano-prodrug was developed for the targeted treatment of OSCC. In this system, the hydrophobic anticancer drug methotrexate (MTX) and the hydrophilic drug gemcitabine (GEM) were conjugated via amide bonds to form an amphiphilic drug-drug conjugate (ADDC), which self-assembled into nanoparticles (MG NPs). Phospholipids were modified with T7 peptide, capable of targeting the highly expressed transferrin receptor (TFR) on tumor cell surfaces, and subsequently loaded onto red blood cell membranes (RBCM) to prepare T7 peptide-modified RBCM (T7-RBCM). The MG NPs were then encapsulated with T7-RBCM by co-extrusion to form T7-RBCM@MG NPs. In vitro studies demonstrated that T7-RBCM@MG NPs were more efficiently internalized by tumor cells due to specific recognition between the T7 peptide and TFR, exhibited stronger inhibitory activity against SCC-7 cells, and significantly induced apoptosis. In vivo experiments confirmed that T7-RBCM@MG NPs exhibited favourable biosafety, prolonged circulation, and enhanced tumor-targeting delivery, resulting in significant tumor growth inhibition without notable toxicity to major organs.
研究领域:
肿瘤学
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纳米医学
·
药剂学
·
分子靶向治疗
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转化医学
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生物材料
·
头颈肿瘤
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2018
·Vol. 6
·期 20
·3372-3386
·
IF 4.776
Longbao Feng,Shina Yan,Qiyu Zhu,Jie Chen,Lian Deng,Yanfang Zheng,Wei Xue,Rui Guo
Drug/gene co-delivery carriers are a promising strategy for cancer treatment. Thus, herein, T7-conjugated redox-sensitive amphiphilic polyethylene glycol–polyethyleneimine–poly(caprolactone)-SS-poly(caprolactone)–polyethyleneimine–polyethylene glycol (PEG–PEI–PCL-SS-PCL–PEG) (PPPT) is designed to realize the co-delivery of pORF-hTRAIL and DOX efficiently into tumor cells. PPPT is synthesized via the ring opening polymerization (ROP) of ε-caprolactone followed by Michael addition polymerization and atom transfer radical polymerization (ATRP) of the maleic imide group of MAL-PEG-NHS. The PPPT micelles present a spherical or ellipsoidal geometry with a mean diameter of approximately 100–120 nm. Meanwhile, they also exhibit a redox-responsive drug release profile in vitro. The blood compatibility and complement activation tests reveal that the PPPT micelles do not induce blood hemolysis, blood clotting, or complement activation. The T7-modified co-delivery system shows a higher cellular uptake efficiency than the unmodified co-delivery system in human breast cancer MCF-7 cells and is accumulated in tumor more efficiently in vivo. These results suggest that the T7-targeted codelivery system of DOX and pORF-hTRAIL is a combined delivery platform that can significantly improve the treatment of breast cancer.
研究领域:
癌症治疗
·
药剂学
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2025
·
IF 6.5
Zhecheng Yu,Zeya Zhou,Yunqi Zhao
Background Cancer immunotherapy has achieved great success in breast cancer treatment in recent years. The Programmed Death-1 (PD-1) /Programmed Death-Ligand 1 (PD-L1) immune checkpoint pathway is among the most studied. BMS-1166, a PD-L1 inhibitor, can interfere with PD-1 and PD-L1 interaction. Transferrin Receptor 1 is a transmembrane glycoprotein overexpressed in various cancer cells, including breast cancer, and can specifically interact with the T7 (HAIYPRH) peptide.Purpose This study hypothesized that BMS-1166-loaded T7-modified poly(ethylene glycol)-poly(ε-caprolactone) (PEG-PCL) polymeric micelles (BMS-T7) could block PD-L1 interaction with PD-1, serving as a targeted immunotherapy for TfR1-positive breast cancer.Methods BMS-1166 was encapsulated in T7-PEG-PCL micelle. Particle size and zeta potential were determined by dynamic light scattering. Particle morphology was studied by transmission electron microscopy. The particles were characterized by Fourier transform infrared, thermogravimetric analysis, and differential scanning calorimetry. Drug encapsulation efficiency, loading degree, and release profile were examined by high-performance liquid chromatography. Human breast cancer MDA-MB-231 was used to test the cytotoxicity. Flow cytometry and immunofluorescence imaging were used to study the PD-L1 inhibition in cell surface and exosomes. MDA-MB-231 and Jurkat co-culture studied T-cell activation and apoptosis.Results The particle size of the empty and drug-loaded micelles showed a size distribution with an average diameter of 54.62 ± 2.28 nm and 60.22 ± 2.56 nm, respectively. The encapsulation efficiency of BMS-T7 was 83.89 ± 5.59%. The release half-life of drug-loaded micelles was 48h. The IC50 of BMS-1166 was 28.77 μM in MDA-MB-231 cells. In addition, the BMS-T7 showed a better inhibitory effect on PD-L1 expression in breast cancer cells and exosomes than the naked drug. The formulation significantly restored T-cell function compared to the BMS-1166 treatment.Conclusion These results provide preliminary evidence indicating that BMS-T7 may have the potential to deliver drugs to breast cancer cells via active targeting and hold great promise in cancer immunotherapy drug delivery applications.
研究领域:
肿瘤学
·
药学
·
免疫学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2024
·
IF 4.4
Shuang-Shuang Zhang,Jia-Hui Yu,Si-Si Jiang,Lun Wang,Jiong Chen,Jiao Long,Shuang-Xi Gu,Hui Li
P-glycoprotein (P-gp) overexpressed mutidrug resistance (MDR) is currently a key factor limiting the effectiveness of breast cancer chemotherapy. Systemic administration based on P-gp-associated mechanism leads to severe toxic side effects. Here, we designed a T7 peptide-modified mixed liposome (T7-MLP@DTX/SchB) that, by active targeting co-delivering chemotherapeutic agents and P-gp inhibitors, harnessed synergistic effects to improve the treatment of MDR breast cancer. This study established drug-resistant cell models and animal models. Subsequently, comprehensive evaluations involving cell uptake, cell apoptosis, cellular toxicity assays, in vivo tumor-targeting capability, and anti-tumor activity assays were conducted to assess the drug resistance reversal effects of T7-MLP@DTX/SchB. Additionally, a systematic assessment of the biosafety profile of T7-MLP@DTX/SchB was executed, including blood profiles, biochemical markers, and histopathological examination. It was found that this co-delivery strategy successfully exerted the synergistic effects, since there was a significant tumor growth inhibitory effect on multidrug-resistant breast cancer. Targeted modification with T7 peptide enhanced the therapeutic efficacy remarkably, while vastly ameliorating the biocompatibility compared to free drugs. The intriguing results supported the promising potential use of T7-MLP@DTX/SchB in overcoming MDR breast cancer treatment.
研究领域:
药学
·
肿瘤学
·
生物技术
·
纳米医学
·
癌症治疗
✓ 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）