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Enhanced lysosomal escape of cell penetrating peptide-functionalized metal–organic frameworks for co-delivery of survivin siRNA and oridonin

Cai, Mengru, Yao, Yu, Yin, Dongge, Zhu, Rongyue, Fu, Tingting, Kong, Jiahui, Wang, Kaixin, Liu, Jing, Yao, Aina, Ruan, Yidan, Shi, Wenjuan, Zhu, Qian, Ni, Jian, Yin, Xingbin·2023·Journal of Colloid and Interface Science
DOI 10.1016/j.jcis.2023.04.126
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Abstract

In recent years, small interfering RNA (siRNA) has been widely used in the treatment of human diseases, especially tumors, and has shown great appeal. However, the clinical application of siRNA faces several challenges. Insufficient efficacy, poor bioavailability, poor stability, and lack of responsiveness to a single therapy are the main problems affecting tumor therapy. Here, we designed a cell-penetrating peptide (CPP)-modified metal organic framework nanoplatform (named PEG-CPP33@ORI@survivin siRNA@ZIF-90, PEG-CPP33@NPs) for targeted co-delivery of oridonin (ORI), a natural anti-tumor active ingredient) and survivin siRNA in vivo. This can improve the stability and bioavailability of siRNA and the efficacy of siRNA monotherapy. The high drug-loading capacity and pH-sensitive properties of zeolite imidazolides endowed the PEG-CPP33@NPs with lysosomal escape abilities. The Polyethylene glycol (PEG)-conjugated CPP (PEG-CPP33) coating significantly improved the uptake in the PEG-CPP33@NPs in vitro and in vivo. The results showed that the co-delivery of ORI and survivin siRNA greatly enhanced the anti-tumor effect of PEG-CPP33@NPs, demonstrating the synergistic effect between ORI and survivin siRNA. In summary, the novel targeted nanobiological platform loaded with ORI and survivin siRNA presented herein showed great advantages in cancer therapy, and provides an attractive strategy for the synergistic application of chemotherapy and gene therapy.

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Metadata

Authors
Cai, M., Yao, Y., Yin, D., Zhu, R., Fu, T., Kong, J., Wang, K., Liu, J., Yao, A., Ruan, Y., Shi, W., Zhu, Q., Ni, J., & Yin, X.
Venue
Journal of Colloid and Interface Science
Publisher
Elsevier BV
Published
2023-09
Volume
646
Pages
370-380
ISSN
0021-9797
DOI
10.1016/j.jcis.2023.04.126
Cited by
45
References
1
Language
en
Licence
Funders
  • Natural Science Foundation of Beijing Municipality (7202121)
  • National Natural Science Foundation of China (81703715)

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