BACKGROUND: Liposomes, used to improve the therapeutic index of new and established drugs, have advanced with the insertion of active targeting. The lectin from Lotus tetragonolobus (LTL), which binds glycans containing alpha-1,2-linked fucose, reveals surface regionalized glycoepitopes in highly proliferative cells not detectable in normally growing cells. In contrast, other lectins localize the corresponding glycoepitopes all over the cell surface. LTL also proved able to penetrate the cells by an unconventional uptake mechanism. METHODS: We used confocal laser microscopy to detect and localize LTL-positive glycoepitopes and lectin uptake in two cancer cell lines. We then constructed doxorubicin-loaded liposomes functionalized with LTL. Intracellular delivery of the drug was determined in vitro and in vivo by confocal and electron microscopy. RESULTS: We confirmed the specific localization of Lotus binding sites and the lectin uptake mechanism in the two cell lines and determined that LTL-functionalized liposomes loaded with doxorubicin greatly increased intracellular delivery of the drug, compared to unmodified doxorubicin-loaded liposomes. The LTL-Dox-L mechanism of entry and drug delivery was different to that of Dox-L and other liposomal preparations. LTL-Dox-L entered the cells one by one in tiny tubules that never fused with lysosomes. LTL-Dox-L injected in mice with melanoma specifically delivered loaded Dox to the cytoplasm of tumor cells. CONCLUSIONS: Liposome functionalization with LTL promises to broaden the therapeutic potential of liposomal doxorubicin treatment, decreasing non-specific toxicity. GENERAL SIGNIFICANCE: Doxorubicin-LTL functionalized liposomes promise to be useful in the development of new cancer chemotherapy protocols.

DELLA GIOVAMPAOLA, C., Capone, A., Ermini, L., Lupetti, P., Vannuccini, E., Finetti, F., et al. (2017). Formulation of liposomes functionalized with the Lotus lectin and effective in targeting highly proliferative cells. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 1861(4), 860-870 [10.1016/j.bbagen.2017.01.015].

Formulation of liposomes functionalized with the Lotus lectin and effective in targeting highly proliferative cells

DELLA GIOVAMPAOLA, CINZIA;CAPONE, ANTONIETTA;ERMINI, LEONARDO;LUPETTI, PIETRO;VANNUCCINI, ELISA;FINETTI, FEDERICA;DONNINI, SANDRA;ZICHE, MARINA;MAGNANI, AGNESE;LEONE, GEMMA;ROSSI, CLAUDIO;ROSATI, FLORIANA;BONECHI, CLAUDIA
2017-01-01

Abstract

BACKGROUND: Liposomes, used to improve the therapeutic index of new and established drugs, have advanced with the insertion of active targeting. The lectin from Lotus tetragonolobus (LTL), which binds glycans containing alpha-1,2-linked fucose, reveals surface regionalized glycoepitopes in highly proliferative cells not detectable in normally growing cells. In contrast, other lectins localize the corresponding glycoepitopes all over the cell surface. LTL also proved able to penetrate the cells by an unconventional uptake mechanism. METHODS: We used confocal laser microscopy to detect and localize LTL-positive glycoepitopes and lectin uptake in two cancer cell lines. We then constructed doxorubicin-loaded liposomes functionalized with LTL. Intracellular delivery of the drug was determined in vitro and in vivo by confocal and electron microscopy. RESULTS: We confirmed the specific localization of Lotus binding sites and the lectin uptake mechanism in the two cell lines and determined that LTL-functionalized liposomes loaded with doxorubicin greatly increased intracellular delivery of the drug, compared to unmodified doxorubicin-loaded liposomes. The LTL-Dox-L mechanism of entry and drug delivery was different to that of Dox-L and other liposomal preparations. LTL-Dox-L entered the cells one by one in tiny tubules that never fused with lysosomes. LTL-Dox-L injected in mice with melanoma specifically delivered loaded Dox to the cytoplasm of tumor cells. CONCLUSIONS: Liposome functionalization with LTL promises to broaden the therapeutic potential of liposomal doxorubicin treatment, decreasing non-specific toxicity. GENERAL SIGNIFICANCE: Doxorubicin-LTL functionalized liposomes promise to be useful in the development of new cancer chemotherapy protocols.
DELLA GIOVAMPAOLA, C., Capone, A., Ermini, L., Lupetti, P., Vannuccini, E., Finetti, F., et al. (2017). Formulation of liposomes functionalized with the Lotus lectin and effective in targeting highly proliferative cells. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 1861(4), 860-870 [10.1016/j.bbagen.2017.01.015].
File in questo prodotto:
File Dimensione Formato  
BBA2017_lipoLectinaDox.pdf

non disponibili

Tipologia: PDF editoriale
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 3.06 MB
Formato Adobe PDF
3.06 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
BONECHI-Formulation of liposomes-BBA2017 accepted manuscript.pdf

accesso aperto

Descrizione: Accepted Manuscript
Tipologia: Post-print
Licenza: Creative commons
Dimensione 6.41 MB
Formato Adobe PDF
6.41 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/1004600