Journal
JOURNAL OF CONTROLLED RELEASE
Volume 278, Issue -, Pages 127-139Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2018.04.005
Keywords
Size-reducible; Size screen; Nitro oxide; Combinational therapy; Theranostic
Funding
- National Natural Science Foundation of China [31571016]
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The size of nanoparticles plays a key role in utilizing enhanced permeability and retention (EPR) effect of tumor, where large-sized nanoparticles possess good retention but poor penetration, while small-sized nanoparticles are on the contrary. Although size-reducible nanoparticles have been designed to partially overcome this dilemma, the initial size and complicated tumor microenvironment remain restricting the tumor distribution of nanoparticles. Herein, we employed tumor-specific CD44 targeted, hyaluronidase-degradable hyaluronic acid (HA) and small-sized, renal-clearable, red emission, cationic bovine serum albumin-protected gold nanocluster (AuNC@CBSA) to successfully construct size-reducible nanoplatform (AuNC@CBSA@HA). By changing the ratio of HA and AuNC@CBSA, different initial sizes of AuNC@CBSA@HA were prepared and their tumor targeting efficiencies, pharmacokinetic profiles were evaluated. Then 200 nm of AuNC@CBSA@HA with optimal EPR effect was screened out to further load paclitaxel (PTX) and indocyanine green (ICG) for chemo-photothermal therapy and nitric oxide (NO) for modulating tumor microenvironment and enhancing drug delivery. The AuNC@CBSA-PTX-ICG@HA-NO3 showed size-reducible ability under triggering by hyaluronidase and high accumulation in breast cancer with homogenous intra-tumor distribution, suppressed 95.3% of in-situ tumor growth and inhibited 88.4% of lung metastasis growth. In conclusion, we provide a strategy that fully satisfied the concerns in drug delivery to tumor for improved antitumor effect.
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