Dual-pH Sensitive Charge-Reversal Drug Delivery System for Highly Precise and Penetrative Chemotherapy
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RESEARCH PAPER
Dual-pH Sensitive Charge-Reversal Drug Delivery System for Highly Precise and Penetrative Chemotherapy Weiguo Chen 1 & Ji Li 1 & Yan Xing 2 & Xiaowei Wang 3 & Hongyan Zhang 3 & Mingyu Xia 2 & Dongkai Wang 3
Received: 22 February 2020 / Accepted: 4 June 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
ABSTRACT Purpose The complex physiological barriers impose extremely conflicting demands on systemic drug delivery, so both particle size and surface charge of the nanoplatforms become vital factors. As a carbon-based nanomaterial with excellent optical properties, carbon dots are not suitable for direct systemic transport in vivo, which limits their application in the field of biomedical imaging, especially in the areas of diagnosis and cancer treatment. Liposomes have been developed as universal nanocarriers for various drugs. In this study, we aimed to build a highly precise
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11095-020-02852-6) contains supplementary material, which is available to authorized users. * Mingyu Xia [email protected] * Dongkai Wang [email protected] Weiguo Chen [email protected] Ji Li [email protected] Yan Xing [email protected] Xiaowei Wang [email protected]
and penetrative drug delivery system (DDS) using carbon dots encapsulated by liposomes. Methods Carbon dots (CDs) were synthesized by the hydrothermal method using citric acid and ethylenediamine. Furthermore, simian virus 40 large T-antigen derived the nuclear targeting sequence (NLS) was bonded on the surface of CDs to obtain CDsNLS. The antitumor drug doxorubicin was loaded onto the CDsNLS through an acid-labile hydrazine bond to obtain DOX@CDs. Finally, DOX@CDs were encapsulated in aqueous centers of folate-coated and pH-sensitive liposomes, named pHSL-FA. Results In this paper, a nucleus-targeted nanocomposite (DOX@CDs), which bonds with the nuclear targeting sequence (NLS) and the anticancer drug doxorubicin (DOX), has physicochemical properties of particle size of about 3.8 nm, zeta potential of +31.8 mV and high quantum yield of 64.53%. The negatively charged folate-coated and pH-sensitive liposomes (pHSL-FA) are used as a carrier to reverse the surface charge of DOX@CDs. Compared to free DOX@CDs, pHSL-FA show higher tumor accumulation in 4 T1 tumor-bearing mice and further improve cytotoxicity to tumor cells. Conclusions This work proposes a unique nanomedical approach that enables the precise delivery of chemotherapy drugs and significantly reduces side effects, which is promising for clinical translation.
KEY WORDS bioimaging . carbon dots . doxorubicin . folate . liposomes . pH-sensitive
Hongyan Zhang [email protected] 1
Department of Traditional Chinese Medicine, Shenyang Pharmaceutical University, No.103, Wenhua Road, Shenyang 110016, China
ABBREVIATIONS
2
Department of Pharmacology, Shenyang Pharmaceutical University, No.103, Wenhua Road, Shenyang 110016, China
DOX NLS
3
Department of Pharmaceutics, S
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