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Cisplatin encapsulation within a ferritin nanocage: a high-resolution crystallographic study
Nicola Pontillo1, Francesca Pane1, Luigi Messori2
1Department of Chemical Sciences, University of Naples Federico II, Complesso Universitario di Monte Sant'Angelo, Via Cintia, I-80126, Napoli, Italy. antonello.merlino@unina.it.
Chemical Communications (Cambridge, England)
|February 19, 2016
Summary
Cisplatin (CDDP) can be encapsulated in apoferritin (AFt) for targeted cancer therapy. X-ray crystallography revealed CDDP binds to His132 on AFt
Area of Science:
- Biochemistry
- Nanotechnology
- Structural Biology
Background:
- Ferritin is a protein cage that can encapsulate drugs.
- Cisplatin (CDDP) is a platinum-based chemotherapy drug.
- Encapsulating CDDP in apoferritin (AFt) offers potential for targeted cancer treatment.
Purpose of the Study:
- To investigate the interaction between cisplatin and apoferritin.
- To determine the binding site of cisplatin within the apoferritin structure.
- To assess the suitability of CDDP-encapsulated AFt as a nanocarrier.
Main Methods:
- High-resolution X-ray crystallography.
- Difference Fourier electron density map analysis.
- Anomalous dispersion data analysis.
Main Results:
- Cisplatin (CDDP) binds to the His132 residue on the inner surface of apoferritin (AFt).
- A [Pt(NH3)2H2O](2+) fragment is identified as the bound platinum species.
- The outer surface properties of the AFt nanocage remain unchanged upon CDDP encapsulation.
Conclusions:
- CDDP-encapsulated AFt is a promising nanocarrier for targeted drug delivery.
- The AFt nanocage maintains its structural integrity and biocompatibility.
- Internalization via receptor-mediated endocytosis enhances selective delivery to tumor tissues.
