Local and Systemic Antitumor Effects of Photo-activatable Paclitaxel Prodrug on Rat Breast Tumor Models

Bharathiraja Subramaniyan, Pallavi Rajaputra, Luong Nguyen, Mengjie Li, Cody J. Peer, Jessica Kindrick, William D. Figg, Sukyung Woo, Youngjae You*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

We demonstrated that a large primary and a small untreated distant breast cancer could be controlled by local treatment with our light-activatable paclitaxel (PTX) prodrug. We hypothesized that the treated tumor would be damaged by the combinational effects of photodynamic therapy (PDT) and locally released PTX and that the distant tumor would be suppressed by systemic antitumor effects. Syngeneic rat breast cancer models (single- and two-tumor models) were established on Fischer 344 rats by subcutaneous injection of MAT B III cells. The rats were injected with PTX prodrug (dose: 1 umole kg−1, i.v.), and tumors were treated with illumination using a 690-nm laser (75 or 140 mW cm−1 for 30 min, cylindrical light diffuser, drug-light interval [DLI] 9 h). Larger tumors (~16 mm) were effectively ablated (100%) without recurrence for >90 days. All cured rats rejected rechallenged tumor for up to 12 months. In the two-tumor model, the treatment of the local large tumor (~16 mm) also cured the untreated tumor (4–6 mm) through adaptive immune activation. This is our first demonstration that local treatment with our PTX prodrug produces systemic antitumor effects. Further investigations are warranted to understand mechanisms and optimal conditions to achieve clinically translatable systemic antitumor effects.

Original languageEnglish
Pages (from-to)668-679
Number of pages12
JournalPhotochemistry and Photobiology
Volume96
Issue number3
DOIs
StatePublished - 1 May 2020
Externally publishedYes

Fingerprint

Dive into the research topics of 'Local and Systemic Antitumor Effects of Photo-activatable Paclitaxel Prodrug on Rat Breast Tumor Models'. Together they form a unique fingerprint.

Cite this