Key result
SpHL-DOX-Fol significantly increased cytotoxicity in FR+ breast cancer cells and decreased systemic renal and cardiac toxic effects compared to free DOX, even at a higher dose of 20 mg/kg.
Why the study?
New strategies are sought to improve doxorubicin delivery and antitumor activity while avoiding side effects, requiring elucidation of folate functionalization in SpHL-DOX across cell types and complete safety evaluation.
Does SpHL-DOX-Fol improve antitumor activity and reduce cardiotoxicity compared to free DOX and SpHL-DOX in preclinical models?
Does SpHL-DOX-Fol improve antitumor activity and reduce cardiotoxicity compared to free DOX and SpHL-DOX in preclinical models?
Folate-coated pH-sensitive liposomal doxorubicin enhances targeted antitumor activity in folate receptor-positive breast cancer cells while reducing systemic and cardiac toxicity in preclinical models.
May enable safer doxorubicin dosing in FR+ models; leaves open clinical translation for reduced cardiotoxicity.
Doxorubicin (DOX) loaded liposomes have been used and studied in the last decades due to the significant decrease in DOX induced cardiac and systemic toxicity relative to administration of free drug. Therefore, new strategies are sought to improve DOX delivery and antitumor activity, while avoiding side effects. Recently, folate-coated pH-sensitive liposomes (SpHL-Fol) have been studied as a tool to enhance cellular uptake and antitumor activity of paclitaxel and DOX in breast cancer cells expressing folate receptor (FR+). However, the elucidation of folate functionalization relevance in DOX-loaded SpHL (SpHL-DOX-Fol) in different cell types (MDA-MB-231, MCF-7, and A549), as well as, the complete safety evaluation, is necessary. To achieve these objectives, SpHL-DOX-Fol was prepared and characterized as previously described. Antitumor activity and acute toxicity were evaluated in vivo through direct comparison of free DOX verses SpHL-DOX, a well-known formulation to reduce DOX cardiotoxicity. The obtained data are crucial to support future translational research. Liposomes showed long-term stability, suitable for biological use. Cellular uptake, cytotoxicity, and percentage of migration inhibition were significantly higher for MDA-MB-231 (FR+) treated with SpHL-DOX-Fol. In addition, SpHL-DOX-Fol demonstrated a decrease in the systemic toxic effects of DOX, mainly in renal and cardiac parameters evaluation, even using a higher dose (20 mg/kg). Collectively these data build the foundation of support demonstrating that SpHL-DOX-Fol could be considered a promising drug delivery strategy for the treatment of FR+ breast tumors.
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Silva et al. (2023) studied FR+ breast cancer. SpHL-DOX-Fol vs. Free DOX and SpHL-DOX was evaluated on Antitumor activity and acute toxicity. SpHL-DOX-Fol significantly increased cytotoxicity in FR+ breast cancer cells and decreased systemic renal and cardiac toxic effects compared to free DOX, even at a higher dose of 20 mg/kg.
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