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Despite great therapeutic effect of Abraxane®, complex preparation technology and unfavorable pharmacokinetics still restricted the clinical application of albumin-based paclitaxel (PTX) nanoparticles (NPs). Herein, we reported that an albumin-binding prodrug, phenylboronic acid-conjugated PTX (P-PTX), can form the uniform NPs with the diameters around 100 nm with the help of albumin via simple one-step nano-precipitation method. The albumin-based nanomedicines were stabilized by the integration of a single boronic acid with PTX due to the increased affinity based on multiple intermolecular interactions. We found that albumin-based P-PTX NPs exhibited superior colloidal stability over albumin-based PTX NPs through one-step nano-precipitation approach, achieving longer in vivo circulation time and higher concentration in tumor than those of the marketed Abraxane®. Furthermore, the albumin-based P-PTX NPs with great stability and enhanced intratumoral enrichment, increased the maximum tolerated dose of PTX, remarkably suppressed the growth of breast tumor and lung metastasis, and prolonged survival of melanoma tumors-bearing mice. Such a convenient and effective system gains an insight into the impact of phenylboronic acid group on the albumin-based PTX NPs, and provides potent strategy for the rational design of albumin-based antitumor nanomedicines.
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