Laminin receptor specific therapeutic gold nanoparticles (198AuNP-EGCg) show efficacy in treating prostate cancer

Ravi Shukla, Nripen Chanda, Ajit Zambre, Anandhi Upendran, Kavita Katti, Rajesh R. Kulkarni, Satish Kumar Nune, Stan W. Casteel, Charles Jeffrey Smith, Jatin Vimal, Evan Boote, J. David Robertson, Para Kan, Hendrik Engelbrecht, Lisa D. Watkinson, Terry L. Carmack, John R. Lever, Cathy S. Cutler, Charles Caldwell, Raghuraman KannanKattesh V. Katti

Research output: Contribution to journalArticle

Abstract

Systemic delivery of therapeutic agents to solid tumors is hindered by vascular and interstitial barriers.We hypothesized that prostate tumor specific epigallocatechin-gallate (EGCg) functionalized radioactive gold nanoparticles, when delivered intratumorally (IT), would circumvent transport barriers, resulting in targeted delivery of therapeutic payloads. The results described herein support our hypothesis. We report the development of inherently therapeutic gold nanoparticles derived from the Au-198 isotope; the range of the198Au β-particle (approximately 11 mm in tissue or approximately 1100 cell diameters) is sufficiently long to provide cross-fire effects of a radiation dose delivered to cells within the prostate gland and short enough to minimize the radiation dose to critical tissues near the periphery of the capsule. The formulation of biocompatible198AuNPs utilizes the redox chemistry of prostate tumor specific phytochemical EGCg as it converts gold salt into gold nanoparticles and also selectively binds with excellent affinity to Laminin67R receptors, which are over expressed in prostate tumor cells. Pharmacokinetic studies in PC-3 xenograft SCID mice showed approximately 72% retention of198AuNP-EGCg in tumors 24 h after intratumoral administration. Therapeutic studies showed 80% reduction of tumor volumes after 28 d demonstrating significant inhibition of tumor growth compared to controls. This innovative nanotechnological approach serves as a basis for designing biocompatible target specific antineoplastic agents. This novel intratumorally injectable198AuNP-EGCg nanotherapeutic agent may provide significant advances in oncology for use as an effective treatment for prostate and other solid tumors.

Original languageEnglish (US)
Pages (from-to)12426-12431
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number31
DOIs
StatePublished - Jul 31 2012
Externally publishedYes

Fingerprint

Laminin Receptors
Gold
Nanoparticles
Prostatic Neoplasms
Prostate
Neoplasms
Therapeutics
SCID Mice
Radiation Effects
Phytochemicals
epigallocatechin gallate
Tumor Burden
Heterografts
Isotopes
Antineoplastic Agents
Oxidation-Reduction
Capsules
Blood Vessels
Pharmacokinetics
Salts

Keywords

  • Cellular targeting
  • Localized therapy
  • Nanoradiotherapy
  • Polyphenols
  • Tumor metastases

ASJC Scopus subject areas

  • General

Cite this

Laminin receptor specific therapeutic gold nanoparticles (198AuNP-EGCg) show efficacy in treating prostate cancer. / Shukla, Ravi; Chanda, Nripen; Zambre, Ajit; Upendran, Anandhi; Katti, Kavita; Kulkarni, Rajesh R.; Nune, Satish Kumar; Casteel, Stan W.; Smith, Charles Jeffrey; Vimal, Jatin; Boote, Evan; Robertson, J. David; Kan, Para; Engelbrecht, Hendrik; Watkinson, Lisa D.; Carmack, Terry L.; Lever, John R.; Cutler, Cathy S.; Caldwell, Charles; Kannan, Raghuraman; Katti, Kattesh V.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, No. 31, 31.07.2012, p. 12426-12431.

Research output: Contribution to journalArticle

Shukla, R, Chanda, N, Zambre, A, Upendran, A, Katti, K, Kulkarni, RR, Nune, SK, Casteel, SW, Smith, CJ, Vimal, J, Boote, E, Robertson, JD, Kan, P, Engelbrecht, H, Watkinson, LD, Carmack, TL, Lever, JR, Cutler, CS, Caldwell, C, Kannan, R & Katti, KV 2012, 'Laminin receptor specific therapeutic gold nanoparticles (198AuNP-EGCg) show efficacy in treating prostate cancer', Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 31, pp. 12426-12431. https://doi.org/10.1073/pnas.1121174109
Shukla, Ravi ; Chanda, Nripen ; Zambre, Ajit ; Upendran, Anandhi ; Katti, Kavita ; Kulkarni, Rajesh R. ; Nune, Satish Kumar ; Casteel, Stan W. ; Smith, Charles Jeffrey ; Vimal, Jatin ; Boote, Evan ; Robertson, J. David ; Kan, Para ; Engelbrecht, Hendrik ; Watkinson, Lisa D. ; Carmack, Terry L. ; Lever, John R. ; Cutler, Cathy S. ; Caldwell, Charles ; Kannan, Raghuraman ; Katti, Kattesh V. / Laminin receptor specific therapeutic gold nanoparticles (198AuNP-EGCg) show efficacy in treating prostate cancer. In: Proceedings of the National Academy of Sciences of the United States of America. 2012 ; Vol. 109, No. 31. pp. 12426-12431.
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AU - Chanda, Nripen

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AU - Upendran, Anandhi

AU - Katti, Kavita

AU - Kulkarni, Rajesh R.

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AU - Smith, Charles Jeffrey

AU - Vimal, Jatin

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AU - Robertson, J. David

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AU - Engelbrecht, Hendrik

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AU - Carmack, Terry L.

AU - Lever, John R.

AU - Cutler, Cathy S.

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AU - Kannan, Raghuraman

AU - Katti, Kattesh V.

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N2 - Systemic delivery of therapeutic agents to solid tumors is hindered by vascular and interstitial barriers.We hypothesized that prostate tumor specific epigallocatechin-gallate (EGCg) functionalized radioactive gold nanoparticles, when delivered intratumorally (IT), would circumvent transport barriers, resulting in targeted delivery of therapeutic payloads. The results described herein support our hypothesis. We report the development of inherently therapeutic gold nanoparticles derived from the Au-198 isotope; the range of the198Au β-particle (approximately 11 mm in tissue or approximately 1100 cell diameters) is sufficiently long to provide cross-fire effects of a radiation dose delivered to cells within the prostate gland and short enough to minimize the radiation dose to critical tissues near the periphery of the capsule. The formulation of biocompatible198AuNPs utilizes the redox chemistry of prostate tumor specific phytochemical EGCg as it converts gold salt into gold nanoparticles and also selectively binds with excellent affinity to Laminin67R receptors, which are over expressed in prostate tumor cells. Pharmacokinetic studies in PC-3 xenograft SCID mice showed approximately 72% retention of198AuNP-EGCg in tumors 24 h after intratumoral administration. Therapeutic studies showed 80% reduction of tumor volumes after 28 d demonstrating significant inhibition of tumor growth compared to controls. This innovative nanotechnological approach serves as a basis for designing biocompatible target specific antineoplastic agents. This novel intratumorally injectable198AuNP-EGCg nanotherapeutic agent may provide significant advances in oncology for use as an effective treatment for prostate and other solid tumors.

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