PMID- 28948461
OWN - NLM
STAT- MEDLINE
DCOM- 20180730
LR  - 20190610
IS  - 1573-904X (Electronic)
IS  - 0724-8741 (Linking)
VI  - 34
IP  - 12
DP  - 2017 Dec
TI  - Co-Delivery of Doxorubicin and Survivin shRNA-Expressing Plasmid Via 
      Microenvironment-Responsive Dendritic Mesoporous Silica Nanoparticles for 
      Synergistic Cancer Therapy.
PG  - 2829-2841
LID - 10.1007/s11095-017-2264-6 [doi]
AB  - PURPOSE: The present study is aimed at designing an appropriate co-delivery 
      system for chemotherapeutic drugs and gene drugs with high loading capacity, 
      on-demand release behaviors, efficient endosomal escape, and enhanced nucleic 
      localization, thereby providing efficacious antitumor activity. METHODS: 
      Schiff-base linked imidazole dendritic mesoporous silica nanoparticles (SL-IDMSN) 
      were developed and employed to load doxorubicin (DOX) and survivin 
      shRNA-expressing plasmid (iSur-pDNA) to form nanocomplexes. The nanoparticles 
      were assessed by structural characterization, drug loading and release, cellular 
      uptake, intracellular distribution, gene transfection, in vitro 
      anti-proliferation of hepatoma cells, and in vivo tumor growth inhibition in H-22 
      tumor bearing mice. RESULTS: SL-IDMSN showed high loading capacity for both DOX 
      and iSur-pDNA due to their hierarchical mesostructures. The cleavage of 
      Schiff-base linkage on SL-IDMSN in the weakly acidic endosomes/lysosomes led to 
      microenvironment-specific release of both DOX and iSur-pDNA. Meanwhile, the 
      imidazole modification could trigger the efficient endosomal escape via proton 
      sponge effect, thereby enhancing nuclear accumulation of iSur-pDNA and gene 
      silencing efficiency. More importantly, these superior performances of SL-IDMSN 
      resulted in their improved inhibitory effects on in vitro cancer cell 
      proliferation and in vivo tumor growth. CONCLUSIONS: SL-IDMSN is a 
      microenvironment-sensitive and biocompatible nanocarrier for the co-delivery of 
      DOX and iSur-pDNA, which might be a promising carrier for co-delivery of 
      chemotherapeutic drugs and gene drugs for synergistic cancer therapy.
FAU - Li, Zhengxiong
AU  - Li Z
AD  - State Key Laboratory of Genetic Engineering, Department of Pharmaceutical 
      Sciences, School of Life Sciences, Fudan University, Shanghai, 200438, China.
FAU - Zhang, Linlin
AU  - Zhang L
AD  - State Key Laboratory of Genetic Engineering, Department of Pharmaceutical 
      Sciences, School of Life Sciences, Fudan University, Shanghai, 200438, China.
FAU - Tang, Cui
AU  - Tang C
AD  - State Key Laboratory of Genetic Engineering, Department of Pharmaceutical 
      Sciences, School of Life Sciences, Fudan University, Shanghai, 200438, China. 
      tangcui@fudan.edu.cn.
FAU - Yin, Chunhua
AU  - Yin C
AD  - State Key Laboratory of Genetic Engineering, Department of Pharmaceutical 
      Sciences, School of Life Sciences, Fudan University, Shanghai, 200438, China.
LA  - eng
GR  - No. 81273460/the National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20170925
PL  - United States
TA  - Pharm Res
JT  - Pharmaceutical research
JID - 8406521
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (BIRC5 protein, human)
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Inhibitor of Apoptosis Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Survivin)
RN  - 7631-86-9 (Silicon Dioxide)
RN  - 80168379AG (Doxorubicin)
SB  - IM
MH  - Animals
MH  - Antibiotics, Antineoplastic/*administration & dosage/therapeutic use
MH  - Cell Line, Tumor
MH  - Delayed-Action Preparations/*chemistry
MH  - Doxorubicin/*administration & dosage/therapeutic use
MH  - Drug Delivery Systems/methods
MH  - Female
MH  - Gene Transfer Techniques
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Inhibitor of Apoptosis Proteins/*genetics
MH  - Mice
MH  - Nanoparticles/chemistry
MH  - Neoplasms/genetics/*therapy
MH  - Plasmids/administration & dosage/genetics
MH  - Porosity
MH  - RNA, Small Interfering/*administration & dosage/genetics/therapeutic use
MH  - *RNAi Therapeutics/methods
MH  - Silicon Dioxide/*chemistry
MH  - Survivin
OTO - NOTNLM
OT  - cancer therapy
OT  - co-delivery
OT  - nanoparticles
OT  - pH responsiveness
EDAT- 2017/09/28 06:00
MHDA- 2018/07/31 06:00
CRDT- 2017/09/27 06:00
PHST- 2017/06/22 00:00 [received]
PHST- 2017/09/14 00:00 [accepted]
PHST- 2017/09/28 06:00 [pubmed]
PHST- 2018/07/31 06:00 [medline]
PHST- 2017/09/27 06:00 [entrez]
AID - 10.1007/s11095-017-2264-6 [pii]
AID - 10.1007/s11095-017-2264-6 [doi]
PST - ppublish
SO  - Pharm Res. 2017 Dec;34(12):2829-2841. doi: 10.1007/s11095-017-2264-6. Epub 2017 
      Sep 25.