Journal
SMALL
Volume 17, Issue 31, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.202100578
Keywords
biological barriers; chemotherapy; drug delivery system; multistage delivery; nanoparticle
Categories
Funding
- National Key Research and Development Programs of China [2018YFA0209700]
- National Natural Science Foundation of China (NSFC) [22077073]
- Fundamental Research Funds for the Central Universities (Nankai University) [ZB19100123, ZB16008705]
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Multistage adaptive nanoparticles (MAN) with a core-shell structure made of responsive polymers can adapt to the biological microenvironment, achieve stability in blood circulation, accumulate in tumor tissues, release drugs effectively in cells, and suppress tumors with reduced systemic toxicity. MAN can load various hydrophobic drugs, providing a general strategy for targeted delivery of hydrophobic drugs to overcome multiple biological barriers and enhance chemotherapy efficacy.
Drug delivery systems (DDS) are extensively studied to improve the solubility, stability, pharmacokinetic, and biodistribution of chemotherapeutics. However, the drug delivery efficiency of traditional DDS is often limited by the complicated biological barriers in vivo. Herein, a multistage adaptive nanoparticle (MAN) that simultaneously overcomes multiple biological barriers to achieve tumor-targeted drug delivery with high efficiency is presented. MAN has a core-shell structure, in which both the core and the shell are made of responsive polymers. This structure allows MAN to present different surface properties to adapt to its surrounding biological microenvironment, thereby achieving enhanced stability in blood circulation, improved tumor accumulation and cellular internalization in tumor tissues, and effective release of drug in cells. With these unique characteristics, the MAN loaded with docetaxel achieves effective tumor suppression with reduced systemic toxicity. Furthermore, MAN can load almost any hydrophobic drugs, providing a general strategy for the tumor-targeted delivery of hydrophobic drugs to overcome the multiple biological barriers and improve the efficacy of chemotherapy.
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