【摘 要】
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The condensed tumor extracellular matrix (ECM) consisting of cross-linked hyaluronic acid (HA) is one of the key factors that result in the aberrant tumor microenvironment and severely impair drug delivery and tumor penetration.Herein,we report a simple d
【机 构】
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State Key Laboratory for Modification of Chemical Fibers and Polymer Materials,College of Chemistry,
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The condensed tumor extracellular matrix (ECM) consisting of cross-linked hyaluronic acid (HA) is one of the key factors that result in the aberrant tumor microenvironment and severely impair drug delivery and tumor penetration.Herein,we report a simple design of a hyaluronidase (HAase)-modified layered double hydroxide (LDH) nanoplatform loaded with anticancer drug doxorubicin (DOX) for enhanced tumor penetration and augmented chemotherapy.In our approach,LDH nanodisks were synthesized via a co-precipitation method,modified with HAase by electrostatic attraction,and finally physically loaded with DOX.The formulated DOX/LDH-HAase complexes show a high DOX loading percentage of 34.2％ with good colloidal stability,retain 86.1％ of the enzyme activity,and release DOX in a pH-responsive manner having a faster release rate under slightly acidic tumor microenvironment than that under a physiological condition.With the catalytic activity of HAase to digest the HA nearby the cancer cells,the developed DOX/LDH-HAase complexes enable more significant uptake by cancer cells and penetration in 3-dimensional tumor spheroids than enzyme-free DOX/LDH complexes,thus displaying much better antitumor efficacy in vitro than the latter.The more significant tumor penetration and inhibition of the DOX/LDH-HAase complexes than that of the DOX/LDH complexes was further demonstrated by in vivo tumor imaging and therapeutic activity assessments.Our study suggests a unique nanomedicine platform combined with both anticancer drug and enzyme for improved tumor penetration and chemotherapy,which is promising for effective chemotherapy of different types of stroma-rich tumors.
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