Targeted TPGS ultrasound-responsive nanodroplets modulate P-gp and mitochondria to enhance doxorubicin sensitivity in multidrug-resistant breast cancer
Year: 2026
Type: article
Abstract: Although drugs targeting mitochondria or P-gp combined with traditional chemotherapy drugs represent a novel and effective treatment for multiple drug resistance (MDR). Nevertheless, the efficacy is still restricted by several obstacles, including significant toxicity. Nanoscale drug delivery systems (DDSs) offer a favourable solution to reduce the toxicity and side effects of systemic administration. Meanwhile, DDSs provide a promising strategy to implement spatially and temporally controlled drug release when combined with ultrasound-targeted microbubble destruction (UTMD). Therefore, novel ultrasonic nanodroplets (NDs) which consist of a shell of D-alpha-tocopheryl polyethylene glycol 1,000 succinate (TPGS) and a core of ultrasound-responsive perfluorohexane, loaded with doxorubicin (DOX) were synthesized in this study to overcome these drawbacks. The encouraging results both in vitro and in vivo indicated that these original NDs exhibit excellent biocompatibility, targeting ability and therapeutic effects. TPGS not only acted as the shell material of NDs, but also had anti-cancer ability in itself. Furthermore, TPGS inhibited the activity of P-gp and thus simultaneously enhanced the sensitivity of DOX they carried. This work was the first to synthesize and report DOX-TPGS-NDs integrating synergistic strategies into a single nanodrug carrier. Our findings may provide scientific evidence to support the potential applications for reversing MDR.
Authors: Ling Ge, Xiaomeng Liu, Yan Sun, Ruo Zhang, Limin Liu, Jie Li
Institutions: Shandong University, Qilu Hospital of Shandong University
Language: English
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7225738332