PMID- 34641857
OWN - NLM
STAT- MEDLINE
DCOM- 20220131
LR  - 20220131
IS  - 1477-3155 (Electronic)
IS  - 1477-3155 (Linking)
VI  - 19
IP  - 1
DP  - 2021 Oct 12
TI  - Improving anti-cancer drug delivery performance of magnetic mesoporous silica 
      nanocarriers for more efficient colorectal cancer therapy.
PG  - 314
LID - 10.1186/s12951-021-01056-3 [doi]
LID - 314
AB  - BACKGROUND: Improving anti-cancer drug delivery performance can be achieved 
      through designing smart and targeted drug delivery systems (DDSs). For this aim, 
      it is important to evaluate overexpressed biomarkers in the tumor 
      microenvironment (TME) for optimizing DDSs. MATERIALS AND METHODS: Herein, we 
      designed a novel DDS based on magnetic mesoporous silica core-shell nanoparticles 
      (SPION@MSNs) in which release of doxorubicin (DOX) at the physiologic pH was 
      blocked with gold gatekeepers. In this platform, we conjugated heterofunctional 
      polyethylene glycol (PEG) onto the outer surface of nanocarriers to increase 
      their biocompatibility. At the final stage, an epithelial cell adhesion molecule 
      (EpCAM) aptamer as an active targeting moiety was covalently attached 
      (Apt-PEG-Au@NPs-DOX) for selective drug delivery to colorectal cancer (CRC) 
      cells. The physicochemical properties of non-targeted and targeted nanocarriers 
      were fully characterized. The anti-cancer activity, cellular internalization, and 
      then the cell death mechanism of prepared nanocarriers were determined and 
      compared in vitro. Finally, tumor inhibitory effects, biodistribution and 
      possible side effects of the nanocarriers were evaluated in immunocompromised 
      C57BL/6 mice bearing human HT-29 tumors. RESULTS: Nanocarriers were successfully 
      synthesized with a mean final size diameter of 58.22 +/- 8.54 nm. Higher 
      cytotoxicity and cellular uptake of targeted nanocarriers were shown in the 
      EpCAM-positive HT-29 cells as compared to the EpCAM-negative CHO cells, 
      indicating the efficacy of aptamer as a targeting agent. In vivo results in a 
      humanized mouse model showed that targeted nanocarriers could effectively 
      increase DOX accumulation in the tumor site, inhibit tumor growth, and reduce the 
      adverse side effects. CONCLUSION: These results suggest that corporation of a 
      magnetic core, gold gatekeeper, PEG and aptamer can strongly improve drug 
      delivery performance and provide a theranostic DDS for efficient CRC therapy.
CI  - (c) 2021. The Author(s).
FAU - Iranpour, Sonia
AU  - Iranpour S
AD  - Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, 
      Mashhad, Iran.
FAU - Bahrami, Ahmad Reza
AU  - Bahrami AR
AD  - Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, 
      Mashhad, Iran.
AD  - Industrial Biotechnology Research Group, Institute of Biotechnology, Ferdowsi 
      University of Mashhad, Mashhad, Iran.
FAU - Nekooei, Sirous
AU  - Nekooei S
AD  - Department of Radiology, Faculty of Medicine, Mashhad University of Medical 
      Sciences, Mashhad, Iran.
FAU - Sh Saljooghi, Amir
AU  - Sh Saljooghi A
AD  - Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, 
      Mashhad, Iran. saljooghi@um.ac.ir.
AD  - Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, 
      Ferdowsi University of Mashhad, Mashhad, Iran. saljooghi@um.ac.ir.
FAU - Matin, Maryam M
AU  - Matin MM
AUID- ORCID: 0000-0002-7949-7712
AD  - Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, 
      Mashhad, Iran. matin@um.ac.ir.
AD  - Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, 
      Ferdowsi University of Mashhad, Mashhad, Iran. matin@um.ac.ir.
LA  - eng
GR  - 3.51537/Ferdowsi University of Mashhad/
PT  - Journal Article
DEP - 20211012
PL  - England
TA  - J Nanobiotechnology
JT  - Journal of nanobiotechnology
JID - 101152208
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Drug Carriers)
RN  - 7631-86-9 (Silicon Dioxide)
RN  - 80168379AG (Doxorubicin)
SB  - IM
MH  - Animals
MH  - *Antineoplastic Agents/chemistry/pharmacokinetics/pharmacology
MH  - CHO Cells
MH  - Colorectal Neoplasms/*metabolism
MH  - Cricetinae
MH  - Cricetulus
MH  - Doxorubicin/chemistry/pharmacokinetics/pharmacology
MH  - *Drug Carriers/chemistry/pharmacokinetics
MH  - HT29 Cells
MH  - Humans
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - *Nanoparticles/chemistry/metabolism
MH  - *Silicon Dioxide/chemistry/pharmacokinetics
PMC - PMC8507230
OTO - NOTNLM
OT  - Colorectal cancer
OT  - Drug delivery system
OT  - Magnetic mesoporous silica NPs
OT  - Targeted therapy
OT  - Theranostic
OT  - pH-sensitive gatekeeper
COIS- The authors declare that there is no conflict of interest.
EDAT- 2021/10/14 06:00
MHDA- 2022/02/01 06:00
PMCR- 2021/10/12
CRDT- 2021/10/13 05:39
PHST- 2021/08/16 00:00 [received]
PHST- 2021/09/21 00:00 [accepted]
PHST- 2021/10/13 05:39 [entrez]
PHST- 2021/10/14 06:00 [pubmed]
PHST- 2022/02/01 06:00 [medline]
PHST- 2021/10/12 00:00 [pmc-release]
AID - 10.1186/s12951-021-01056-3 [pii]
AID - 1056 [pii]
AID - 10.1186/s12951-021-01056-3 [doi]
PST - epublish
SO  - J Nanobiotechnology. 2021 Oct 12;19(1):314. doi: 10.1186/s12951-021-01056-3.