Development of Novel Paclitaxel-Loaded ZIF-8 Metal-Organic Framework Nanoparticles Modified with Peptide Dimers and an Evaluation of Its Inhibitory Effect against Prostate Cancer Cells

Author:

Zhao Heming1,Gong Liming1ORCID,Wu Hao2,Liu Chao1ORCID,Liu Yanhong1,Xiao Congcong1,Liu Chenfei1,Chen Liqing1,Jin Mingji1,Gao Zhonggao1,Guan Youyan3,Huang Wei1

Affiliation:

1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

2. Department of Pharmacy, Yanbian University, Yanji 133000, China

3. Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China

Abstract

Prostate cancer (PC) is one of the common malignant tumors of the male genitourinary system. Here, we constructed PTX@ZIF-8, which is a metal-organic-framework-encapsulated drug delivery nanoparticle with paclitaxel (PTX) as a model drug, and further modified the synthesized peptide dimer (Di-PEG2000-COOH) onto the surface of PTX@ZIF-8 to prepare a nanotargeted drug delivery system (Di-PEG@PTX@ZIF-8) for the treatment of prostate cancer. This study investigated the morphology, particle size distribution, zeta potential, drug loading, encapsulation rate, stability, in vitro release behavior, and cytotoxicity of this targeted drug delivery system, and explored the uptake of Di-PEG@PTX@ZIF-8 by human prostate cancer Lncap cells at the in vitro cellular level, as well as the proliferation inhibition and promotion of apoptosis of Lncap cells by the composite nanoparticles. The results suggest that Di-PEG@PTX@ZIF-8, as a zeolitic imidazolate frameworks-8-loaded paclitaxel nanoparticle, has promising potential for the treatment of prostate cancer, which may provide a novel strategy for the delivery system targeting prostate cancer.

Funder

CAMS Innovation Fund for Medical Sciences

National Natural Science Foundation of China

Bethune Urinary Cancer Special Research Fund

CSCO Navigation Cancer Research Fund

Bethune Cancer Basic Research Program Project

Publisher

MDPI AG

Subject

Pharmaceutical Science

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