Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 11, Issue 46, Pages 42904-42916Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.9b13556
Keywords
mitochondrial targeting; immunogenic cell death; photochemotherapy; immunotherapy; breast cancer
Funding
- National Natural Science Foundation of China (NSFC) [21872083, 21573134]
- Shandong Provincial Major Science AMP
- Technology Innovation Project [2018CXGC1411]
- Natural Science Foundation of Shandong Province [ZR2018PH043]
- Fundamental Research Funds of Shandong University [2018JC019]
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Potentiating systemic immunity against breast cancer is in the most urgent demand as breast cancer is less sensitive to immune checkpoint blockade. Although phototherapy and some chemotherapy can trigger immunogenic cell death (ICD) for T cell-mediated antitumor immune response, their immunotherapy efficacy is severely restricted by insufficient phototherapeutic capability and severe multidrug resistance (MDR). Inspired by both the hypersensitivity to phototherapy and the key role of MDR for mitochondria, a rationally engineered immunity amplifier via mitochondria-targeted photochemotherapeutic nanoparticles was, for the first time, achieved to fight against low-immunogenic breast cancer without additional immune agents. The newly synthesized task-specific mitochondria-targeted IR780 derivative (T780) was integrated with chemotherapeutic doxorubicin (DOX) to form multifunctional nanoparticles via an assembling strategy along with bovine serum albumin (BSA) as a biomimetic corona (BSA@T780/DOX NPs). The in situ enhancement in both phototherapy and MDR reversal by targeting mitochondria with BSA@T780/DOX NPs boosted highly efficient ICD toward excellent antitumor immune response. The newly developed strategy not only eradicated the primary tumor but also eliminated the bilateral tumors efficiently, as well as preventing metastasis and postsurgical recurrence, demonstrating great interest for fighting against low-immunogenic breast cancer.
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