Hyaluronic acid-targeted and pH-responsive drug delivery system based on metal-organic frameworks for efficient antitumor therapy

Qianqian Sun; Huiting Bi; Zhao Wang; Chunxia Li; Xuwei Wang; Jiating Xu; Hui Zhu; Ruoxi Zhao; Fei He; Shili Gai; Piaoping Yang

doi:10.1016/j.biomaterials.2019.119473

Hyaluronic acid-targeted and pH-responsive drug delivery system based on metal-organic frameworks for efficient antitumor therapy

Biomaterials. 2019 Dec:223:119473. doi: 10.1016/j.biomaterials.2019.119473. Epub 2019 Sep 3.

Authors

Qianqian Sun¹, Huiting Bi¹, Zhao Wang², Chunxia Li³, Xuwei Wang¹, Jiating Xu¹, Hui Zhu¹, Ruoxi Zhao¹, Fei He¹, Shili Gai⁴, Piaoping Yang⁵

Affiliations

¹ Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Material Sciences and Chemical Engineering, Harbin Engineering University, Harbin, 150001, PR China.
² Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Material Sciences and Chemical Engineering, Harbin Engineering University, Harbin, 150001, PR China; College of Sciences, Heihe University, Heihe, 164300, PR China.
³ Key Laboratory of the Ministry of Education for Advanced Catalysis Materials, Zhejiang Normal University, Jinhua, Zhejiang, 321004, PR China.
⁴ Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Material Sciences and Chemical Engineering, Harbin Engineering University, Harbin, 150001, PR China. Electronic address: gaishili@hrbeu.edu.cn.
⁵ Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Material Sciences and Chemical Engineering, Harbin Engineering University, Harbin, 150001, PR China; College of Sciences, Heihe University, Heihe, 164300, PR China. Electronic address: yangpiaoping@hrbeu.edu.cn.

PMID: 31499255
DOI: 10.1016/j.biomaterials.2019.119473

Abstract

Drug delivery systems (DDSs) have emerged to help delivering the required cargo into the region of the tumor, achieving the objectives of extenuating the potential damage to the body and improving the therapeutic effectiveness. Here, we developed a one-pot process for encapsulating the unstable and hydrophobic d-α-Tocopherol succinate (α-TOS) in zeolitic imidazolate framework-8 (ZIF-8) compounds (defined as α-TOS@ZIF-8) and subsequently coated with a hyaluronic acid (HA) shell to form the HA/α-TOS@ZIF-8 nanoplatform. Of particular note was when the concentration of α-TOS is l mg/mL, the loading rate was high up to 43.03 wt%. The study verified that HA shell, which could act as a smart "switch" and tumor-targeted "guider", had the capacity for extending blood circulation, enhancing the tumor-specific accumulation of DDS via CD44-mediated pathway. HA shell could be disintegrated by hyaluronidase (HAase) in the tumor microenvironment (TME) and the wrapped α-TOS@ZIF-8 exposed, thus leading to the decomposition of ZIF-8 in tumor acidic microenvironment to release the loaded α-TOS. Therefore, the HA/α-TOS@ZIF-8 nanoplatform has been achieved as a tumor-specific and on-demand drug delivery system, which improved the treatment efficiency.

Keywords: CD44; Drug delivery systems; Hyaluronic acid; Zeolitic imidazolate framework-8; d-α-tocopherol succinate.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / administration & dosage*
Biocompatible Materials
Drug Carriers
Drug Delivery Systems*
Female
HeLa Cells
Hemolysis
Humans
Hyaluronan Receptors / metabolism
Hyaluronic Acid / chemistry*
Hydrogen-Ion Concentration
Imidazoles / chemistry
Light
Metal-Organic Frameworks*
Mice
Microscopy, Electron, Transmission
Nanotechnology / methods
Neoplasm Transplantation
Scattering, Radiation
Temperature
Tumor Microenvironment
Zeolites / chemistry
alpha-Tocopherol / chemistry*

Substances

Antineoplastic Agents
Biocompatible Materials
CD44 protein, human
Drug Carriers
Hyaluronan Receptors
Imidazoles
Metal-Organic Frameworks
acidified zeolitic imidazolate framework-8
Zeolites
Hyaluronic Acid
alpha-Tocopherol