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Local and Systemic Antitumor Effects of Photo‐activatable Paclitaxel Prodrug on Rat Breast Tumor Models
Author(s) -
Subramaniyan Bharathiraja,
Rajaputra Pallavi,
Nguyen Luong,
Li Mengjie,
Peer Cody J.,
Kindrick Jessica,
Figg William D.,
Woo Sukyung,
You Youngjae
Publication year - 2020
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/php.13202
Subject(s) - prodrug , paclitaxel , medicine , breast cancer , pharmacology , photodynamic therapy , chemotherapy , doxorubicin , cancer research , cancer , chemistry , organic chemistry
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.