Self-Regulated Multifunctional
Collaboration of Targeted
Nanocarriers for Enhanced Tumor Therapy
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Abstract
Exploring
ideal nanocarriers for drug delivery systems has encountered
unavoidable hurdles, especially the conflict between enhanced cellular
uptake and prolonged blood circulation, which have determined the
final efficacy of cancer therapy. Here, based on controlled self-assembly,
surface structure variation in response to external environment was
constructed toward overcoming the conflict. A novel micelle with mixed
shell of hydrophilic poly(ethylene glycol) PEG and pH responsive hydrophobic
poly(β-amino ester) (PAE) was designed through the self-assembly
of diblock amphiphilic copolymers. To avoid the accelerated clearance
from blood circulation caused by the surface exposed targeting group
c(RGDfK), here c(RGDfK) was conjugated to the hydrophobic PAE and
hidden in the shell of PEG at pH 7.4. At tumor pH, charge conversion
occurred, and c(RGDfK) stretched out of the shell, leading to facilitated
cellular internalization according to the HepG2 cell uptake experiments.
Meanwhile, the heterogeneous surface structure endowed the micelle
with prolonged blood circulation. With the self-regulated multifunctional
collaborated properties of enhanced cellular uptake and prolonged
blood circulation, successful inhibition of tumor growth was achieved
from the demonstration in a tumor-bearing mice model. This novel nanocarrier
could be a promising candidate in future clinical experiments