Nanosponge-encapsulated camptothecin exerts anti-tumor activity in human prostate cancer cells

Rosalba Minelli, Roberta Cavalli, Leigh Ellis, Piergiorgio Pettazzoni, Francesco Trotta, Eric Ciamporcero, Giuseppina Barrera, Roberto Fantozzi, Chiara Dianzani, Roberto Pili

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Camptothecin (CPT) is a potent DNA Topoisomerase I inhibitor with anti-tumor activity in hematological and solid tumors. However, it did not reach clinical use because of its poor solubility and high degrability. β-Cyclodextrin nanosponge (CN) have been demonstrated to be able to increase the solubility of lipophilic compounds and to protect them from degradation. In the present study, we evaluated whether β-Cyclodextrin nanosponge carriers can overcome CPT chemical disadvantages and improve the in vitro anti-tumor efficacy in the androgen refractory models of prostate cancer DU145 and PC-3 and the androgen sensitive model LNCaP. Camptothecin-loaded β-Cyclodextrin nanosponge (CN-CPT) showed sizes of about 400 nm, spherical shape and a drug loading of 38%. HPLC analysis, performed on the cell pellet after treatment with CN-CPT revealed that CPT concentration increased over time indicating a prolonged release of the drug. Moreover, CN-CPT inhibited Topoisomerase I activity, and induced DNA damage, and cell cycle arrest more effectively than CPT, indicating that the CN-CPT formulation does not affect activity of the drug. Moreover, Annexin V/Propidium Iodide staining showed an induction of cell death at low concentrations that were not effective for CTP. LNCaP cells were less sensitive to CPT than PC-3 and DU145 cells, but CN-CPT still exerted higher anti-proliferative activity and DNA damage ability than CPT. The experiments performed in LNCaP cells demonstrated that CN-CPT treatment inhibited expression of the androgen receptor at doses where CPT was ineffective. Our results demonstrated the higher anti-tumor effectiveness of CN-CPT compare to CPT in prostate cancer cells, supporting the relevance of future studies for the use of the β-Cyclodextrin nanosponge to deliver anticancer drugs in vivo.

Original languageEnglish (US)
Pages (from-to)686-694
Number of pages9
JournalEuropean Journal of Pharmaceutical Sciences
Volume47
Issue number4
DOIs
StatePublished - Nov 20 2012
Externally publishedYes

Fingerprint

Camptothecin
Human Activities
Prostatic Neoplasms
Cyclodextrins
Neoplasms
Solubility
Androgens
DNA Damage
Pharmaceutical Preparations
Topoisomerase I Inhibitors
Cytidine Triphosphate
Type I DNA Topoisomerase
Propidium
Annexin A5
Androgen Receptors
Cell Cycle Checkpoints

Keywords

  • β-Cyclodextrin nanosponge
  • Androgen receptor
  • Camptothecin
  • DNA damage
  • DNA Topoisomerase I
  • Prostate cancer

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Nanosponge-encapsulated camptothecin exerts anti-tumor activity in human prostate cancer cells. / Minelli, Rosalba; Cavalli, Roberta; Ellis, Leigh; Pettazzoni, Piergiorgio; Trotta, Francesco; Ciamporcero, Eric; Barrera, Giuseppina; Fantozzi, Roberto; Dianzani, Chiara; Pili, Roberto.

In: European Journal of Pharmaceutical Sciences, Vol. 47, No. 4, 20.11.2012, p. 686-694.

Research output: Contribution to journalArticle

Minelli, R, Cavalli, R, Ellis, L, Pettazzoni, P, Trotta, F, Ciamporcero, E, Barrera, G, Fantozzi, R, Dianzani, C & Pili, R 2012, 'Nanosponge-encapsulated camptothecin exerts anti-tumor activity in human prostate cancer cells', European Journal of Pharmaceutical Sciences, vol. 47, no. 4, pp. 686-694. https://doi.org/10.1016/j.ejps.2012.08.003
Minelli, Rosalba ; Cavalli, Roberta ; Ellis, Leigh ; Pettazzoni, Piergiorgio ; Trotta, Francesco ; Ciamporcero, Eric ; Barrera, Giuseppina ; Fantozzi, Roberto ; Dianzani, Chiara ; Pili, Roberto. / Nanosponge-encapsulated camptothecin exerts anti-tumor activity in human prostate cancer cells. In: European Journal of Pharmaceutical Sciences. 2012 ; Vol. 47, No. 4. pp. 686-694.
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AU - Ciamporcero, Eric

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