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Updated: Apr 12, 2026

Engineering Cell-permeable Protein
Published on: December 28, 2009
[The application of enzyme-sensitive activatable cell-penetrating peptides to targeted delivery system]
Abstract:
Cell-penetrating peptides (CPPs) offer a non-selective and receptor-independent mode to promote cellular uptake. Although the non-specificity of CPP-mediated internalization allows this approach applicable to a wide range of tumor types potentially, their universality is a significant obstacle to their clinical utility for targeted delivery of cancer therapeutics and imaging agents. Accordingly, many reports have focused on selective switching of systemically delivered inert CPPs into their active form in lesions (tumor). In this review, our attention is mainly confined to such an enzyme-sensitive domain incorporated delivery system with activatable CPPs (ACPPs), which have displayed the exciting strength in balancing the CPPs' pros and cons, and potential in the treatment and diagnosis of some diseases.
Insights
Activatable cell-penetrating peptides (ACPPs) offer a solution to the non-specific uptake challenge of CPPs. These modified peptides can be activated in tumors, enhancing targeted delivery for cancer therapeutics and diagnostics.
Area of Science:
- Biochemistry
- Molecular Biology
- Nanotechnology
Background:
- Cell-penetrating peptides (CPPs) facilitate non-selective, receptor-independent cellular uptake.
- The broad applicability of CPPs is hindered by their lack of specificity, posing challenges for targeted cancer therapies.
- Strategies are being developed to switch systemically delivered CPPs into an active form specifically at tumor sites.
Purpose of the Study:
- To review the advancements in activatable CPPs (ACPPs) for targeted delivery.
- To highlight the potential of enzyme-sensitive ACPPs in overcoming CPP limitations.
- To discuss the application of ACPPs in disease treatment and diagnosis.
Main Methods:
- Focus on enzyme-sensitive domain incorporated delivery systems.
- Review of literature on activatable CPPs (ACPPs).
- Analysis of strategies for selective CPP activation in target lesions.
Main Results:
- ACPPs demonstrate a promising balance between the advantages and disadvantages of CPPs.
- Enzyme-sensitive ACPPs show potential for targeted activation within tumors.
- These systems offer improved prospects for disease treatment and diagnosis.
Conclusions:
- Activatable CPPs represent a significant advancement in targeted drug and imaging agent delivery.
- The enzyme-sensitive approach enhances specificity, addressing a key limitation of traditional CPPs.
- ACPPs hold considerable potential for improving cancer therapeutics and diagnostics.
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