An activatable theranostic for targeted cancer therapy and imaging

Sankarprasad Bhuniya, Sukhendu Maiti, Eun Joong Kim, Hyunseung Lee, Jonathan L. Sessler, Kwan Soo Hong, Jong Seung Kim

Research output: Contribution to journalArticle

136 Citations (Scopus)

Abstract

A new theranostic strategy is described. It is based on the use of an "all in one" prodrug, namely the biotinylated piperazine-rhodol conjugate 4 a. This conjugate, which incorporates the anticancer drug SN-38, undergoes self-immolative cleavage when exposed to biological thiols. This leads to the tumor-targeted release of the active SN-38 payload along with fluorophore 1 a. This release is made selective as the result of the biotin functionality. Fluorophore 1 a is 32-fold more fluorescent than prodrug 4 a. It permits the delivery and release of the SN-38 payload to be monitored easily in?vitro and in?vivo, as inferred from cell studies and ex?vivo analyses of mice xenografts derived from HeLa cells, respectively. Prodrug 4 a also displays anticancer activity in the HeLa cell murine xenograft tumor model. On the basis of these findings we suggest that the present strategy, which combines within a single agent the key functions of targeting, release, imaging, and treatment, may have a role to play in cancer diagnosis and therapy. All in one: A new theranostic prodrug was developed containing a biotinylated piperazine-rhodol conjugate linked to the drug SN-38 through a self-immolative disulfide spacer. When exposed to cellular thiols in cancer cells, it is able to release the active chemotherapeutic, SN38, along with a diagnostic fluorophore. This theranostic framework permits the targeted delivery, release of an active agent (SN-38), and its facile monitoring in vitro and in vivo.

Original languageEnglish
Pages (from-to)4469-4474
Number of pages6
JournalAngewandte Chemie - International Edition
Volume53
Issue number17
DOIs
Publication statusPublished - 2014 Apr 22

Fingerprint

irinotecan
Fluorophores
Prodrugs
Imaging techniques
Tumors
Sulfhydryl Compounds
Heterografts
Cells
Biotin
Monitoring
Disulfides
Pharmaceutical Preparations

Keywords

  • biotin
  • cellular imaging
  • glutathione
  • SN-38
  • theranostic

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis

Cite this

An activatable theranostic for targeted cancer therapy and imaging. / Bhuniya, Sankarprasad; Maiti, Sukhendu; Kim, Eun Joong; Lee, Hyunseung; Sessler, Jonathan L.; Hong, Kwan Soo; Kim, Jong Seung.

In: Angewandte Chemie - International Edition, Vol. 53, No. 17, 22.04.2014, p. 4469-4474.

Research output: Contribution to journalArticle

Bhuniya, S, Maiti, S, Kim, EJ, Lee, H, Sessler, JL, Hong, KS & Kim, JS 2014, 'An activatable theranostic for targeted cancer therapy and imaging', Angewandte Chemie - International Edition, vol. 53, no. 17, pp. 4469-4474. https://doi.org/10.1002/anie.201311133
Bhuniya, Sankarprasad ; Maiti, Sukhendu ; Kim, Eun Joong ; Lee, Hyunseung ; Sessler, Jonathan L. ; Hong, Kwan Soo ; Kim, Jong Seung. / An activatable theranostic for targeted cancer therapy and imaging. In: Angewandte Chemie - International Edition. 2014 ; Vol. 53, No. 17. pp. 4469-4474.
@article{092df53b9c8e4aa3ade166152f646760,
title = "An activatable theranostic for targeted cancer therapy and imaging",
abstract = "A new theranostic strategy is described. It is based on the use of an {"}all in one{"} prodrug, namely the biotinylated piperazine-rhodol conjugate 4 a. This conjugate, which incorporates the anticancer drug SN-38, undergoes self-immolative cleavage when exposed to biological thiols. This leads to the tumor-targeted release of the active SN-38 payload along with fluorophore 1 a. This release is made selective as the result of the biotin functionality. Fluorophore 1 a is 32-fold more fluorescent than prodrug 4 a. It permits the delivery and release of the SN-38 payload to be monitored easily in?vitro and in?vivo, as inferred from cell studies and ex?vivo analyses of mice xenografts derived from HeLa cells, respectively. Prodrug 4 a also displays anticancer activity in the HeLa cell murine xenograft tumor model. On the basis of these findings we suggest that the present strategy, which combines within a single agent the key functions of targeting, release, imaging, and treatment, may have a role to play in cancer diagnosis and therapy. All in one: A new theranostic prodrug was developed containing a biotinylated piperazine-rhodol conjugate linked to the drug SN-38 through a self-immolative disulfide spacer. When exposed to cellular thiols in cancer cells, it is able to release the active chemotherapeutic, SN38, along with a diagnostic fluorophore. This theranostic framework permits the targeted delivery, release of an active agent (SN-38), and its facile monitoring in vitro and in vivo.",
keywords = "biotin, cellular imaging, glutathione, SN-38, theranostic",
author = "Sankarprasad Bhuniya and Sukhendu Maiti and Kim, {Eun Joong} and Hyunseung Lee and Sessler, {Jonathan L.} and Hong, {Kwan Soo} and Kim, {Jong Seung}",
year = "2014",
month = "4",
day = "22",
doi = "10.1002/anie.201311133",
language = "English",
volume = "53",
pages = "4469--4474",
journal = "Angewandte Chemie - International Edition",
issn = "1433-7851",
publisher = "John Wiley and Sons Ltd",
number = "17",

}

TY - JOUR

T1 - An activatable theranostic for targeted cancer therapy and imaging

AU - Bhuniya, Sankarprasad

AU - Maiti, Sukhendu

AU - Kim, Eun Joong

AU - Lee, Hyunseung

AU - Sessler, Jonathan L.

AU - Hong, Kwan Soo

AU - Kim, Jong Seung

PY - 2014/4/22

Y1 - 2014/4/22

N2 - A new theranostic strategy is described. It is based on the use of an "all in one" prodrug, namely the biotinylated piperazine-rhodol conjugate 4 a. This conjugate, which incorporates the anticancer drug SN-38, undergoes self-immolative cleavage when exposed to biological thiols. This leads to the tumor-targeted release of the active SN-38 payload along with fluorophore 1 a. This release is made selective as the result of the biotin functionality. Fluorophore 1 a is 32-fold more fluorescent than prodrug 4 a. It permits the delivery and release of the SN-38 payload to be monitored easily in?vitro and in?vivo, as inferred from cell studies and ex?vivo analyses of mice xenografts derived from HeLa cells, respectively. Prodrug 4 a also displays anticancer activity in the HeLa cell murine xenograft tumor model. On the basis of these findings we suggest that the present strategy, which combines within a single agent the key functions of targeting, release, imaging, and treatment, may have a role to play in cancer diagnosis and therapy. All in one: A new theranostic prodrug was developed containing a biotinylated piperazine-rhodol conjugate linked to the drug SN-38 through a self-immolative disulfide spacer. When exposed to cellular thiols in cancer cells, it is able to release the active chemotherapeutic, SN38, along with a diagnostic fluorophore. This theranostic framework permits the targeted delivery, release of an active agent (SN-38), and its facile monitoring in vitro and in vivo.

AB - A new theranostic strategy is described. It is based on the use of an "all in one" prodrug, namely the biotinylated piperazine-rhodol conjugate 4 a. This conjugate, which incorporates the anticancer drug SN-38, undergoes self-immolative cleavage when exposed to biological thiols. This leads to the tumor-targeted release of the active SN-38 payload along with fluorophore 1 a. This release is made selective as the result of the biotin functionality. Fluorophore 1 a is 32-fold more fluorescent than prodrug 4 a. It permits the delivery and release of the SN-38 payload to be monitored easily in?vitro and in?vivo, as inferred from cell studies and ex?vivo analyses of mice xenografts derived from HeLa cells, respectively. Prodrug 4 a also displays anticancer activity in the HeLa cell murine xenograft tumor model. On the basis of these findings we suggest that the present strategy, which combines within a single agent the key functions of targeting, release, imaging, and treatment, may have a role to play in cancer diagnosis and therapy. All in one: A new theranostic prodrug was developed containing a biotinylated piperazine-rhodol conjugate linked to the drug SN-38 through a self-immolative disulfide spacer. When exposed to cellular thiols in cancer cells, it is able to release the active chemotherapeutic, SN38, along with a diagnostic fluorophore. This theranostic framework permits the targeted delivery, release of an active agent (SN-38), and its facile monitoring in vitro and in vivo.

KW - biotin

KW - cellular imaging

KW - glutathione

KW - SN-38

KW - theranostic

UR - http://www.scopus.com/inward/record.url?scp=84899032171&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84899032171&partnerID=8YFLogxK

U2 - 10.1002/anie.201311133

DO - 10.1002/anie.201311133

M3 - Article

C2 - 24644015

AN - SCOPUS:84899032171

VL - 53

SP - 4469

EP - 4474

JO - Angewandte Chemie - International Edition

JF - Angewandte Chemie - International Edition

SN - 1433-7851

IS - 17

ER -