2. Academic Validation
  3. A drug-delivery depot for epigenetic modulation and enhanced cancer immunotherapy

A drug-delivery depot for epigenetic modulation and enhanced cancer immunotherapy

  • Biomed Pharmacother. 2023 Oct 12:168:115687. doi: 10.1016/j.biopha.2023.115687.
Junzhong Lai 1,  Jiadi Liang 2,  Yong Zhang 2,  Bingchen Zhang 3,  Jianhui Wei 2,  Jiqiang Fan 2,  Linqin Chen 2,  Zhirong Chen 2,  Qiumei Li 2,  Dong Guo 2,  Jizhen Lin 4,  Qi Chen 5
Affiliations

Affiliations

  • 1 The Cancer Center, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, PR China.
  • 2 Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, Fujian Normal University, Fuzhou, Fujian 350117, PR China.
  • 3 Department of Oncology, Affiliated Dongguan Hospital, Southern Medical University, Dongguan, Guangdong 523058, PR China.
  • 4 The Cancer Center, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, PR China. Electronic address: [email protected].
  • 5 Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, Fujian Normal University, Fuzhou, Fujian 350117, PR China. Electronic address: [email protected].
PMID: 37837882 DOI: 10.1016/j.biopha.2023.115687
Abstract

DNA Methyltransferase inhibitors (DNMTis) have found widespread application in the management of Cancer. Zebularine (Zeb), functioning as a demethylating agent, has exhibited notable advantages and enhanced therapeutic efficacy in the realm of tumour immunotherapy. Nevertheless, due to its lack of targeted functionality, standalone Zeb therapy necessitates the administration of a substantially higher dosage. In this investigation, we have devised an innovative nanodrug formulation, comprising the DNA Methyltransferase Inhibitor Zeb and pH-responsive chitosan (CS), hereinafter referred to as CS-Zeb nanoparticles (NPs). Our findings have unveiled that CS-Zeb NPs manifest heightened drug release within an acidic milieu (pH 5.5) in comparison to a neutral environment (pH 7.4). Furthermore, in vivo studies have conclusively affirmed that, in contrast to equivalent quantities of Zeb in isolation, the nanocomplex significantly curtailed tumour burden and protracted the survival duration of the B16F10 tumour-bearing murine model. Additionally, CS-Zeb NPs elicited an augmentation of CD8+ T cells within the peripheral circulation of mice and tumour-infiltrating lymphocytes (TILs). Notably, the dosage of CS-Zeb NPs was reduced by a remarkable 70-fold when juxtaposed with Zeb administered in isolation. To summarise, our study underscores the potential of CS-Zeb NPs as an alternative chemotherapeutic agent for Cancer treatment.

Keywords

Cancer treatment; Chitosan; DNA methyltransferase inhibitors; Tumour immunotherapy; Zebularine.

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