NANOTECHNOLOGY
·
2019
·Vol. 30
·期 14
·145601
·
IF 3.399
Yuan Zhong,Yi Wang,Li Luo,Deti Nurhidayah,Ali Maruf,Hans Gregersen,Wei Wu,Gui-Xue Wang
The development of the tumor-targeting ability of nanocarriers is of paramount importance for gene delivery into tumor lesions as well as to avoid biotoxicity. Here we report the synthesis of the polyethyleneimine-fluorescein isothiocyanate-folic acid (PEI-FITC-FA) polymer, which could condense the tumor suppressor pp53 to form nanocomplexes. These targeted nanocomplexes exhibited favorable physical properties including a small size of <100 nm, exploiting the enhanced permeability and retention effect and tumor-targeting ability by binding to the overexpressed FA receptors on tumor cell surfaces. In addition, once the nanocomplexes are accumulating in the tumor tissue, the target functional ligand, FA, can selectively recognize the over-expressed FA receptor and subsequently remain on the tumor cell surface, which can significantly promote the tumor cell uptake because of the time- and concentration-dependent internalization caused by the enhanced interaction between nanocomplex and tumor cell. Our results indicated that PEI-FITC-FA/pp53 nanocomplexes could be efficiently delivered into tumor cells, and subsequently induce tumor cell apoptosis. Thus, the targeted cationic polymer PEI-FITC-FA could be used as an advanced nanocarrier for gene delivery.
研究领域:
药学
·
生物技术
·
纳米技术
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
POLYMER INTERNATIONAL
·
2014
·Vol. 64
·期 5
·647-653
·
IF 2.247
Ping Liang,Chao-Qun Wang,Hong Chen,Ren-Xi Zhuo,Si-Xue Cheng
A facile strategy for the fabrication of multi-functional polymer/inorganic hybrid nanoparticles for efficient gene and drug co-delivery was developed. A therapeutic gene (p53 plasmid) and a chemotherapy drug (doxorubicin hydrochloride, DOX) were co-loaded simultaneously in hybrid nanoparticles during co-precipitation with high encapsulation efficiency. The prepared heparin–biotin/heparin/CaCO 3 /calcium phosphate/DNA/DOX (HPB/HP/CaCO 3 /CaP/DNA/DOX) nanoparticles exhibited pH sensitivity and tumor-targeting property due to the presence of the CaCO 3 /CaP inorganic component and biotin moiety in the polymer chain, respectively. For comparison, HPB/HP/CaCO 3 /CaP/DOX hybrid nanoparticles for drug delivery were also fabricated. The cell inhibition effects of different nanoparticles on HeLa cells were evaluated using methylthiazole tetrazolium assay. In vitro study indicated that the gene and drug co-delivery system (HPB/HP/CaCO 3 /CaP/DNA/DOX) showed a stronger cell growth inhibition effect as compared with the drug delivery system (HPB/HP/CaCO 3 /CaP/DOX), indicating that HPB/HP/CaCO 3 /CaP/DNA/DOX hybrid nanoparticles could effectively mediate gene transfection and deliver the drug. The hybrid nanoparticles with good biocompatibility have great promise for gene and drug co-delivery. © 2014 Society of Chemical Industry
研究领域:
纳米技术
·
药剂学
·
分子生物学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2023
·
IF 5.8
Mengdi Song,Zhou Fang,Jun Wang,Kehai Liu
Ovarian cancer (OC) has a low five-year survival rate, mainly because of its drug resistance to chemotherapy. It is the key to reverse drug resistance to combine multiple sensitization pathways to play a synergistic role. A nano scaled targeted co-delivery system (P123-PEI-G12, PPG) modified by bifunctional peptide tLyP-1-NLS (G12) was fabricated by using Pluronic P123 conjugated with low molecular weight polyethyleneimine (PEI). This delivery system can co-delivery Olaparib (Ola) and p53 plasmids to synergistically enhance the sensitivity of OC to platinum-based chemotherapy. [email protected] /Ola (Co-PPGs) can achieve efficient tumor accumulation and cellular internalization through G12-mediated targeting. Co-PPGs then break down in the tumor cells, releasing the drug. Co-PPGs significantly enhanced the sensitivity of cisplatin (DDP) in platinum-resistant ovarian cancer (PROC) and synergistically inhibited the proliferation of PROC in vitro and in vivo . The sensitizing and synergistic effects of Co-PPGs were related to the activation of p53, inhibition of poly-ADP-ribose polymerase (PARP) and p-glycoprotein (P-gp) expression. This work provides a promising strategy for the effective treatment of PROC.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2015
·
IF 8.557
Si Chen,Lei Rong,Qi Lei,Peng-Xi Cao,Si-Yong Qin,Di-Wei Zheng,Hui-Zhen Jia,Jing-Yi Zhu,Si-Xue Cheng,Ren-Xi Zhuo,Xian-Zheng Zhang
To improve the tumor therapeutic efficiency and reduce undesirable side effects, ternary FK/p53/PEG-PLL(DA) complexes with a detachable surface shielding layer were designed. The FK/p53/PEG-PLL(DA) complexes were fabricated by coating the folate incorporated positively charged FK/p53 complexes with charge-switchable PEG-shield (PEG-PLL(DA)) through electrostatic interaction . At the physiological pH 7.4 in the bloodstream, PEG-PLL(DA) could extend the circulating time by shielding the positively charged FK/p53 complexes. After the accumulation of the FK/p53/PEG-PLL(DA) complexes in tumor sites, tumor-acidity-triggered charge switch led to the detachment of PEG-PLL(DA) from the FK/p53 complexes, and resulted in efficient tumor cell entry by folate-mediated uptake and electrostatic attraction . Stimulated by the high content glutathione (GSH) in cytoplasm, the cleavage of disulfide bond resulted in the liberation of proapoptosis peptide C-KLA(TPP) and the p53 gene, which exerted the combined tumor therapy by regulating both intrinsic and extrinsic apoptotic pathways. Both in vitro and in vivo studies confirmed that the ternary detachable complexes FK/p53/PEG-PLL(DA) could enhance antitumor efficacy and reduce adverse effects to normal cells. These findings indicate that the tumor-triggered decomplexation of FK/p53/PEG-PLL(DA) supplies a useful strategy for targeting delivery of different therapeutic agents in synergetic anticancer therapy.
研究领域:
药学
·
癌症生物学
·
纳米技术
·
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）