Mechanism-Based Sonodynamic–Chemo Combinations against Triple-Negative Breast Cancer

Abstract

Due to its noninvasive nature, site-confined irradiation, and high tissue penetrating capabilities, ultrasound (US)-driven sonodynamic treatment (SDT) has been proven to have broad application possibilities in neoplastic and non-neoplastic diseases. However, the inefficient buildup of sonosensitizers in the tumor site remarkably impairs SDT efficiency. The present work proposes a deep-penetrating sonochemistry nanoplatform (Pp18-lipos@SRA737&DOX, PSDL) comprising Pp18 liposomes (Pp18-lipos, Plipo), SRA737 (a CHK1 inhibitor), and doxorubicin (DOX) for the controlled formation of reactive oxygen species (ROS) and release of DOX and SRA737 upon US activation, therefore increasing chemotherapeutic effectiveness and boosting SDT efficacy. Therein, the antitumor activities of DOX have been attributed to its intercalation into the nucleus DNA and induction of cell apoptosis. CHK1 evolved to respond to DNA damage and repair the damage via cell cycle progression. SRA737 is a potent and orally bioavailable clinical drug candidate for inhibiting CHK1, demonstrating adjuvant anticancer effect in vitro and in vivo. It was interesting to find that SRA737 carried into Plipo@DOX could significantly alleviate G2/M cell cycle arrest and aggravate DNA double-strand injuries, resulting in significant cell death. The developed US-switchable nanosystem provides a promising strategy for augmenting sono-chemotherapy against breast cancer controllably and precisely.

Hypophyllanthin and Phyllanthin from Phyllanthus niruri Synergize Doxorubicin Anticancer Properties against Resistant Breast Cancer Cells

“…Our study revealed a prominent G 2 /M phase arrest for MCF-7 ADR cells after DOX treatment, consistent with several previous studies. 47 , 48 This cell cycle arrest-induced stress ultimately induces apoptosis in breast cancer. 40 On the contrary, DOX-treated MCF-7 ADR cells after co-treatment with hypophyllanthin and phyllanthin were markedly accumulated in the G 0 /G 1 phase, suggesting that hypophyllanthin and phyllanthin distinctly modulated cell cycle arrest induced by DOX and revealed the potential of hypophyllanthin and phyllanthin as co-chemotherapeutic agents.…”

Recent Advances in Targeted Nanocarriers for the Management of Triple Negative Breast Cancer

“…This therapy has been widely used to combat TNBC as the tumor cells of this subtype multiply and progress very fast. Xiaolan Feng et al, proposed a deep-penetrating sonochemistry nanoplatform (Pp18-lipos@SRA737&DOX, PSDL) composed of Pp18 liposomes (Plipo), SRA737 (a CHK1 inhibitor), and doxorubicin (DOX) for the controlled production of reactive oxygen species (ROS) upon ultrasound activation and the resulting intercalation of DOX into the nucleus DNA and induction of cell death [ 108 ]. By enclosing manganese-protoporphyrin (MnP) in folic acid-liposomes, Huaqing Chen et al developed a multifunctional nanosonosensitizer system (FA-MnPs).…”

Cell Membrane–Liposome Hybrid Platform for Ultrasound-Activated Immune-Sonodynamic Therapy for Triple-Negative Breast Cancer

“…Noninvasive treatments for TNBC such as photodynamic therapy (PDT), sonodynamic therapy (SDT), and photothermal therapy (PTT) have recently been developed. − SDT, a comprehensive treatment mode consisting of ultrasound and sonosensitizers, can treat tumors through direct cytotoxicity and further antitumor immunotherapy. Ultrasound, as an external stimulation, has the unique advantage of deep penetration and accurate focus on the tumor tissue.…”