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Lysosomal escaped protein nanocarriers for nuclear-targeted siRNA delivery

Xiuping Cao1,2, Xinxin Shang1,2, Yingshu Guo3,4

  • 1Collaborative Innovation Center of Tumor Marker Detection Technology, Equipment and Diagnosis-Therapy Integration in Universities of Shandong, Shandong Province Key Laboratory of Detection Technology for Tumor Markers, School of Chemistry and Chemical Engineering, Linyi University, Linyi, 276005, China.

Analytical and Bioanalytical Chemistry
|March 26, 2021
PubMed

Insights

This study presents a novel tumor treatment platform using apoferritin (Apn) nanocages for drug delivery. The platform effectively escapes lysosomes, enabling nuclear-targeted siRNA delivery and enhancing cancer treatment efficiency.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Therapy

Background:

  • Lysosomal degradation is a significant challenge in drug carrier design, limiting therapeutic efficacy.
  • Apoferritin (Apn) offers a biocompatible, modifiable, and controllable nanocarrier platform with endogenous properties.
  • Developing strategies for lysosomal escape is crucial for improving drug delivery and cancer treatment.

Purpose of the Study:

  • To construct a tumor treatment platform with enhanced lysosomal escape function.
  • To improve the delivery of siRNA to the cell nucleus for efficient gene silencing.
  • To enhance overall cancer treatment efficacy through improved drug delivery.

Main Methods:

  • Engineered aptamer-modified iron-deficient protein nanocages (Apn) to encapsulate siRNA and NLS (nuclear localization signal) with HA peptide.
  • Utilized the acidic lysosomal environment to trigger Apn nanocage cleavage and release of cargo.
  • Leveraged HA peptide for lysosomal membrane disruption and NLS for nuclear targeting of siRNA.

Main Results:

  • The Apn/siRNA/NLS/HA/Apt platform demonstrated effective lysosomal escape.
  • Achieved efficient nuclear delivery of siRNA, leading to significant gene silencing.
  • The nanocarrier system exhibited high biocompatibility and improved cancer treatment effects.

Conclusions:

  • The developed Apn nanocage-based strategy provides a unique lysosomal escape mechanism for nuclear-targeted siRNA delivery.
  • This approach significantly enhances drug delivery and therapeutic efficiency in cancer treatment.
  • The platform shows promise as a biocompatible and effective cancer therapeutic strategy.
Keywords:
ApnCancer cellLysosomal escapeProtein nanocarrierTargeted delivery

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