Skip to main content
construction release_alert
Scholars@Duke will be undergoing maintenance April 11-15. Some features may be unavailable during this time.
cancel
Journal cover image

Intratumoral delivery of brachytherapy and immunotherapy by a thermally triggered polypeptide depot.

Publication ,  Journal Article
Kelly, G; Milligan, JJ; Mastria, EM; Kim, S; Zelenetz, SR; Dobbins, J; Cai, LY; Li, X; Nair, SK; Chilkoti, A
Published in: J Control Release
March 2022

Biomaterial-based approaches for a combination of radiotherapy and immunotherapy can improve outcomes in metastatic cancer through local delivery of both therapeutic modalities to the primary tumor to control local tumor growth and distant metastases. This study describes an injectable depot for sustained intratumoral (i.t.) delivery of an iodine-131 (131I) radionuclide and a CpG oligodeoxynucleotide immunostimulant, driven by the thermally sensitive phase transition behavior of elastin-like polypeptides (ELPs). We synthesized and characterized an ELP with an oligolysine tail (ELP-K12) that forms an electrostatic complex with CpG for delivery from an ELP depot and evaluated the ability of the complex to enhance local and systemic tumor control as a monotherapy and in combination with 131I-ELP brachytherapy. I.t delivery of CpG from an ELP-K12 depot dramatically prolongs i.t. retention to more than 21 days as compared to soluble CpG that is only retained within the tumor for <24 h. ELP-K12 also enhances CpG delivery by increasing cellular uptake of CpG to generate greater toll-like receptor 9 (TLR9) activation than CpG alone. I.t. treatment with an ELP-K12/CpG depot slows primary tumor growth and reduces lung metastases in a poorly immunogenic 4 T1 syngeneic breast cancer model whereas i.t treatment of CpG alone has no significant effect on primary tumor growth or metastases. Notably, a combination of 131I-ELP brachytherapy and ELP-K12/CpG delivered i.t. inhibited 4 T1 tumor growth and strongly decreased the development of lung metastases, leading to a synergistic improvement in mouse survival. These preclinical results demonstrate that injectable ELP depots may provide a useful approach for the delivery of combination radio- and immuno-therapy to treat metastatic disease.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Control Release

DOI

EISSN

1873-4995

Publication Date

March 2022

Volume

343

Start / End Page

267 / 276

Location

Netherlands

Related Subject Headings

  • Pharmacology & Pharmacy
  • Peptides
  • Neoplasms
  • Mice
  • Iodine Radioisotopes
  • Immunotherapy
  • Elastin
  • Brachytherapy
  • Animals
  • 4003 Biomedical engineering
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kelly, G., Milligan, J. J., Mastria, E. M., Kim, S., Zelenetz, S. R., Dobbins, J., … Chilkoti, A. (2022). Intratumoral delivery of brachytherapy and immunotherapy by a thermally triggered polypeptide depot. J Control Release, 343, 267–276. https://doi.org/10.1016/j.jconrel.2022.01.024
Kelly, Garrett, Joshua J. Milligan, Eric M. Mastria, Sarah Kim, Stephanie R. Zelenetz, Jarrett Dobbins, Leon Y. Cai, Xinghai Li, Smita K. Nair, and Ashutosh Chilkoti. “Intratumoral delivery of brachytherapy and immunotherapy by a thermally triggered polypeptide depot.J Control Release 343 (March 2022): 267–76. https://doi.org/10.1016/j.jconrel.2022.01.024.
Kelly G, Milligan JJ, Mastria EM, Kim S, Zelenetz SR, Dobbins J, et al. Intratumoral delivery of brachytherapy and immunotherapy by a thermally triggered polypeptide depot. J Control Release. 2022 Mar;343:267–76.
Kelly, Garrett, et al. “Intratumoral delivery of brachytherapy and immunotherapy by a thermally triggered polypeptide depot.J Control Release, vol. 343, Mar. 2022, pp. 267–76. Pubmed, doi:10.1016/j.jconrel.2022.01.024.
Kelly G, Milligan JJ, Mastria EM, Kim S, Zelenetz SR, Dobbins J, Cai LY, Li X, Nair SK, Chilkoti A. Intratumoral delivery of brachytherapy and immunotherapy by a thermally triggered polypeptide depot. J Control Release. 2022 Mar;343:267–276.
Journal cover image

Published In

J Control Release

DOI

EISSN

1873-4995

Publication Date

March 2022

Volume

343

Start / End Page

267 / 276

Location

Netherlands

Related Subject Headings

  • Pharmacology & Pharmacy
  • Peptides
  • Neoplasms
  • Mice
  • Iodine Radioisotopes
  • Immunotherapy
  • Elastin
  • Brachytherapy
  • Animals
  • 4003 Biomedical engineering