Tumor microenvironment-specific nanoparticles activatable by stepwise transformation

In an attempt in develop the Lumor-Largeled nanocarrier which can surmount major challenges for in vivu application, we prepared tumor microenvironment-specific nanoparticles which can be sequentially activated at the extracellular and intracellular levels of rumor tissue by stepwise Lransformalion. This polymeric nanoparlide has been prepared using an amphiphilic polyelhyleneimine derivative with the pH-responsive charge-convertible moiety and the reduclion-responsive cTosslink. Once reaching the tumor tissue in vivo after systemic administration, the surface charge of this nanopartide can be converted from negative to positive by recognizing the mildly acidic extracellular matrix of tumor, allowing for the enhanced cellular uptake. After the cellular uptake, the nanoparticle can selectively release the drug at the intracellular level since it has the chemically crosslinked core by the disulfide bond which is cleaved in intracellular reductive environment. The tumor microenvironment-specific nanopartide shows the high tumor targetability and dramatically improves the antitumor efficacy of the drug. (C) 2016 Elsevier B.V. All rights reserved.