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Efficient Tumor Accumulation, Penetration and Tumor Growth Inhibition Achieved by Polymer Therapeutics: The Effect of Polymer Architectures

Abstract

To obtain high tumor-specific accumulation, strong tumor penetration and low off-target uptake, we developed a series of polymer therapeutics with different architectures, including random, block, and brush-like structure, based on the classic N-(2-hydroxypropyl) methacrylamide polymers. The influence of polymer architecture on biological properties such as cellular uptake, blood clearance, and biodistribution have been investigated. Besides small micelles whose sizes were determined by polymer architectures, large aggregates formed by micelle aggregation could also be observed. Although they had different architectures, the drug release rate, endocytic pathways and cellular uptake level of various conjugates have been proved to be identical. The polymer architecture of various conjugates lay great impact on the blood clearance, biodistribution and tumor growth inhibition. We assumed that the differences in in vivo biological properties were coordinately caused by the different size of the small aggregates and the formation and stability of large aggregates for different conjugates. Even though the reason was still unclear, the results inspired us that only by diblock conjugates with improved cellular uptake can we realize tumor specific accumulation, deep penetration, and efficient tumor inhibition

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The Francis Crick Institute

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Last time updated on 12/02/2018

This paper was published in The Francis Crick Institute.

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