Journal
JOURNAL OF CONTROLLED RELEASE
Volume 290, Issue -, Pages 150-164Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2018.10.007
Keywords
Self-assembled and crosslinked nanoparticles; Chemotherapy and sonodynamic therapy (SDT); Reactive oxygen species; Tumor therapy; Drug delivery; Immune response
Funding
- Major Basic Research Project of Shandong Natural Science Foundation, P.R.China [ZR2018HM032]
- Major Research Project of Shandong Province, P.R.China [2018GSF118004]
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Sonodynamic therapy (SDT) has been proposed as a new modality for cancer management through low-intensity ultrasound induced activation of sonosensitizers. Here, we designed a novel redox/enzyme/ultrasound responsive chondroitin sulfate-chlorin e6-lipoic acid nanoplatform loading docetaxel, combining SDT and chemotherapy, for antiproliferation and antimetastasis of melanoma. The reversibly crosslinked and self-assembled nanoparticles possessed monodispersive size distribution, stability in physical conditions, while showing increased uptake with rapid drug release in simulated tumor microenvironment (reductive potentials and degradative hyaluronidase-1). With synthesized ultrasound sensitive polymer backbones, SDT induced the generation of cellular reactive oxygen species and mitochondrial damage, exerting the apoptotic effect through the release of cytochrome C, the expression of cleaved caspase-9 followed by the functional cleaved caspase-3. Chemo-sonodynamic therapy not only inhibited tumor growth and metastasis with reduced metastatic protein expression, but also caused immune response via the release of tumor-associated antigens. It was initially demonstrated that SDT could induce the tumor cell death, therefore having potentials to recruit cytotoxic lymphocytes into tumor sites. Notably, the nanoplatforms exhibited good in vivo stability and blood compatibility, indicating the safety and efficiency in drug delivery. Our work thus presents a convenient approach to fabricate intelligent multifunctional nanoparticles and paves a path for effective cancer therapies.
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