본문 바로가기
HOME> 논문 > 논문 검색상세

논문 상세정보

Acta Biomaterialia: structure-property-function relationships in biomaterials v.70, 2018년, pp.177 - 185   SCI SCIE SCOPUS
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

Lung cancer specific and reduction-responsive chimaeric polymersomes for highly efficient loading of pemetrexed and targeted suppression of lung tumor in vivo

Yang, Weijing (Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, PR China ) ; Yang, Liang (Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, PR China ) ; Xia, Yifeng (Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, PR China ) ; Cheng, Liang (Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, PR China ) ; Zhang, Jian (Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design ) ; Meng, Fenghua ; Yuan, Jiandong ; Zhong, Zhiyuan ;
  • 초록  

    Abstract Lung cancer is one of the worldwide leading and fast-growing malignancies. Pemetrexed disodium (PEM, Alimta?), a small hydrophilic drug, is currently used for treating lung cancer patients. However, PEM suffers from issues like fast elimination, low bioavailability, poor tumor cell selectivity and penetration. Here, we report on lung cancer specific CSNIDARAC (CC 9 ) peptide-functionalized reduction-responsive chimaeric polymersomes (CC 9 -RCPs) for efficient encapsulation and targeted delivery of PEM to H460 human lung cancer cells in vitro and in vivo . PEM-loaded CC 9 -RCPs (PEM-CC 9 -RCPs) was obtained from co-self-assembly of poly(ethylene glycol)- b -poly(trimethylene carbonate- co -dithiolane trimethylene carbonate)- b -polyethylenimine (PEG-P(TMC-DTC)-PEI) and CC 9 -functionalized PEG-P(TMC-DTC) in the presence of PEM followed by self-crosslinking. PEM-CC 9 -RCPs displayed an optimal CC 9 density of 9.0% in targeting H460 cells, a high PEM loading content of 14.2 wt%, a small hydrodynamic size of ca. 60 nm and glutathione-triggered PEM release. MTT assays showed that PEM-CC 9 -RCPs was 2.6- and 10- fold more potent to H460 cells than the non-targeting PEM-RCPs and free PEM controls, respectively. Interestingly, PEM-CC 9 -RCPs exhibited 22-fold longer circulation time and 9.1-fold higher accumulation in H460 tumor than clinical formulation Alimta?. Moreover, CC 9 -RCPs showed obviously better tumor penetration than RCPs. Remarkably, PEM-CC 9 -RCPs at 12.5 mg PEM equiv./kg effectively suppressed growth of H460 xenografts and significantly prolonged mouse survival time as compared to PEM-RCPs and Alimta? controls. These lung cancer specific and reduction-responsive chimaeric polymersomes provide a unique pemetrexed nanoformulation for targeted lung cancer therapy. Statement of Significance Multitargeted antifolate agent pemetrexed (PEM, Alimta?) is currently used for treating lung cancer patients and has low side-effects. However, PEM suffers from issues like fast elimination, low bioavailability, poor tumor cell selectivity and penetration. Scarce work on targeted delivery of PEM has been reported, partly because most conventional nanocarriers show a low and instable loading for hydrophilic, negatively charged drugs like PEM. Herewith, we report on lung cancer specific CSNIDARAC (CC 9 ) peptide-functionalized reduction-responsive chimaeric polymersomes (CC 9 -RCPs) which showed efficient PEM encapsulation (14.2 wt%, 60 nm) and targeted delivery of PEM to H460 human lung cancer cells, leading to effective suppression of H460 tumor xenografts and significantly prolonged survival rates of mice than Alimta?. To the best of our knowledge, this represents a first report on targeted nanosystems that are capable of efficient loading and targeted delivery of PEM to lung tumors. Graphical abstract [DISPLAY OMISSION]


  • 주제어

    Polymersomes .   Reduction-sensitive .   Targeted delivery .   Pemetrexed .   Lung cancer.  

 활용도 분석

  • 상세보기

    amChart 영역
  • 원문보기

    amChart 영역

원문보기

무료다운로드
  • 원문이 없습니다.

유료 다운로드의 경우 해당 사이트의 정책에 따라 신규 회원가입, 로그인, 유료 구매 등이 필요할 수 있습니다. 해당 사이트에서 발생하는 귀하의 모든 정보활동은 NDSL의 서비스 정책과 무관합니다.

원문복사신청을 하시면, 일부 해외 인쇄학술지의 경우 외국학술지지원센터(FRIC)에서
무료 원문복사 서비스를 제공합니다.

NDSL에서는 해당 원문을 복사서비스하고 있습니다. 위의 원문복사신청 또는 장바구니 담기를 통하여 원문복사서비스 이용이 가능합니다.

이 논문과 함께 출판된 논문 + 더보기