PMID- 29742345
OWN - NLM
STAT- MEDLINE
DCOM- 20190710
LR  - 20190710
IS  - 1526-4602 (Electronic)
IS  - 1525-7797 (Linking)
VI  - 19
IP  - 7
DP  - 2018 Jul 9
TI  - Tumor Specific and Renal Excretable Star-like Triblock Polymer-Doxorubicin 
      Conjugates for Safe and Efficient Anticancer Therapy.
PG  - 2849-2862
LID - 10.1021/acs.biomac.8b00425 [doi]
AB  - Efficient tumor accumulation and body clearance are two paralleled requirements 
      for ideal nanomedicines. However, it is hard for both to be met simultaneously. 
      The inefficient clearance often restrains the application of drug delivery 
      systems (DDSs), especially for high-dosage administration. In this study, the 
      star-like and block structures are combined to enhance the tumor specific 
      targeting of the parent structures and obtain additional renal excretion 
      property. The influences of polymer architectures and chemical compositions on 
      the physicochemical and biological properties, particularly the simultaneous 
      achievement of tumor accumulation and renal clearance, have been investigated. 
      Among the tested conjugates, an eight-arm triblock star polymer based on 
      poly(ethylene glycol) (PEG) and poly( N-(2-hydroxyl) methacrylamide) (PHPMA) is 
      found to simultaneously fulfill the requirements of superior tumor accumulation 
      and efficient renal clearance due to the appropriate micelle size and reversible 
      aggregation process. On the basis of this conjugate, 60 mg/kg of Dox equivalent 
      (much higher than the maximum tolerated dose (MTD) of Dox) can be administered to 
      efficiently suppress tumor growth without causing any obvious toxicity. This work 
      provides a new approach to design polymer-drug conjugates for tumor specific 
      application, which can simultaneously address the efficacy and safety concerns.
FAU - Tang, Hao
AU  - Tang H
FAU - Zhang, Jiajing
AU  - Zhang J
AD  - The Key Laboratory of Geriatrics , Beijing Hospital and Beijing Institute of 
      Geriatrics, Chinese Ministry of Health , Beijing 100730 , China.
FAU - Tang, Jin
AU  - Tang J
FAU - Shen, Yi
AU  - Shen Y
FAU - Guo, Wenxuan
AU  - Guo W
FAU - Zhou, Min
AU  - Zhou M
FAU - Wang, Ruihua
AU  - Wang R
FAU - Jiang, Ni
AU  - Jiang N
FAU - Gan, Zhihua
AU  - Gan Z
FAU - Yu, Qingsong
AU  - Yu Q
AUID- ORCID: 0000-0003-2165-3054
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180521
PL  - United States
TA  - Biomacromolecules
JT  - Biomacromolecules
JID - 100892849
RN  - 0 (Acrylamides)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Nanoconjugates)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 80168379AG (Doxorubicin)
RN  - K67NG89J77 (methacrylamide)
SB  - IM
MH  - Acrylamides/chemistry
MH  - Animals
MH  - Antineoplastic Agents/*administration & dosage/pharmacokinetics/therapeutic use
MH  - Cell Line, Tumor
MH  - Doxorubicin/*administration & dosage/analogs & derivatives/pharmacokinetics
MH  - Female
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Nanoconjugates/adverse effects/*chemistry
MH  - Polyethylene Glycols/chemistry
MH  - Renal Elimination
MH  - Tissue Distribution
EDAT- 2018/05/10 06:00
MHDA- 2019/07/11 06:00
CRDT- 2018/05/10 06:00
PHST- 2018/05/10 06:00 [pubmed]
PHST- 2019/07/11 06:00 [medline]
PHST- 2018/05/10 06:00 [entrez]
AID - 10.1021/acs.biomac.8b00425 [doi]
PST - ppublish
SO  - Biomacromolecules. 2018 Jul 9;19(7):2849-2862. doi: 10.1021/acs.biomac.8b00425. 
      Epub 2018 May 21.