Citation: Yunjie Dang, Yanru Feng, Xiao Chen, Chaoxing He, Shujie Wei, Dingyang Liu, Jinlong Qi, Huaxing Zhang, Shaokun Yang, Zhiyun Niu, Bai Xiang. Development of a multi-level pH-responsive lipid nanoplatform for efficient co-delivery of siRNA and small-molecule drugs in tumor treatment[J]. Chinese Chemical Letters, ;2024, 35(12): 109660. doi: 10.1016/j.cclet.2024.109660 shu

Development of a multi-level pH-responsive lipid nanoplatform for efficient co-delivery of siRNA and small-molecule drugs in tumor treatment

Yunjie Dang ^{a, 1} ,
Yanru Feng ^{a, b, 1} ,
Xiao Chen ^{a, 1} ,
Chaoxing He ^a ,
Shujie Wei ^a ,
Dingyang Liu ^a ,
Jinlong Qi ^c ,
Huaxing Zhang ^c ,
Shaokun Yang ^{a, *,} ,
Zhiyun Niu ^{d, *,} ,
Bai Xiang ^{a, *,}

a.
Department of Pharmaceutics, Hebei Medical University, Shijiazhuang 050017, China
b.
Department of Pharmacy, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
c.
Core Facilities and Centers, Hebei Medical University, Shijiazhuang 050017, China
d.
Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China

yangshaokun@hebmu.edu.cn

zhiyunniu@hebmu.edu.cn

baixiang@hebmu.edu.cn

Received Date: 9 December 2023
Revised Date: 8 February 2024
Accepted Date: 15 February 2024
Available Online: 17 February 2024

Figures(4)

The combination of nucleic acid and small-molecule drugs in tumor treatment holds significant promise; however, the precise delivery and controlled release of drugs within the cytoplasm encounter substantial obstacles, impeding the advancement of formulations. To surmount the challenges associated with precise drug delivery and controlled release, we have developed a multi-level pH-responsive co-loaded drug lipid nanoplatform. This platform first employs cyclic cell-penetrating peptides to exert a multi-level pH response, thereby enhancing the uptake efficiency of tumor cells and endow the nanosystem with effective endosomal/lysosomal escape. Subsequently, small interferring RNA (siRNA) complexes are formed by compacting siRNA with stearic acid octahistidine, which is capable of responding to the lysosome-to-cytoplasm pH gradient and facilitate siRNA release. The siRNA complexes and docetaxel are simultaneously encapsulated into liposomes, thereby creating a lipid nanoplatform capable of co-delivering nucleic acid and small-molecule drugs. The efficacy of this platform has been validated through both in vitro and in vivo experiments, affirming its significant potential for practical applications in the co-delivery of nucleic acids and small-molecule drugs.
- Cyclic peptides,
- siRNA,
- Liposomal platform,
- Multi-level pH-responsive,
- Co-delivery
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