Abstract 51P
Background
Ultrasound (US)-activated sonodynamic therapy (SDT) stands for a distinct antitumor modality because of its attractive characteristics including intriguing noninvasiveness, desirable safety, and high tissue penetration depth, which, unfortunately, suffers from compromised therapeutic efficacy due to cancer cell-inherent adaptive mechanisms, such as glutathione (GSH) neutralization response to reactive oxygen species (ROS), and glutamine addictive properties of tumors.
Methods
In this work, we developed a biological sonosensitive platelet (PLT) pharmacytes for favoring US/GSH-responsive combinational therapeutic of glutamine deprivation and augmented SDT. The amino acid transporter SLC6A14 blockade agent α-methyl-DL-tryptophan (α-MT)-loaded and MnO2-coated por- phyrinic metal-organic framework (MOF) nanoparticles were encapsulated in the PLTs through the physical adsorption of electrostatic attraction and the intrinsic endocytosis of PLTs.
Results
When the sonosensitive PLT phar- macytes reached tumor sites through their natural tendencies to TME, US stimulated the PLTs-loaded porphyrinic MOF to generate ROS, resulting in morphological changes of the PLTs and the release of nanoparticles. Subse- quently, intracellular high concentration of GSH and extracellular spatio-temporal controlled US irradiation programmatically triggered the release of α-MT, which enabled the synergistically amplified SDT by inducing amino acid starvation, inhibiting mTOR, and mediating ferroptosis. In addition, US stimulation achieved the targeted activation of PLTs at tumor vascular site, which evolved from circulating PLTs to dendritic PLTs, effectively blocking the blood supply of tumors through thrombus formation, and revealing the encouraging potential to facilitate tumor therapeutics.
Conclusions
It offers a bioinspired design strategy to improve SDT efficiency, and rends an innovative paradigm for cooperatively ablating refractory tumor.
Clinical trial identification
Legal entity responsible for the study
University of Macau.
Funding
University of Macau.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
89P - Cold atmospheric plasma-activated fluids as a potential new intravesical agent for the treatment of bladder cancer
Presenter: Maria Filomena Botelho
Session: Poster session 09
90P - Discovery of CMPD1 as a tumor-specific cytotoxic microtubule inhibitor
Presenter: Mamoru Takada
Session: Poster session 09
91P - Erythroid precursor-differentiated myeloid cells promote pulmonary metastasis in hepatocellular carcinoma
Presenter: Wei-hang Zhu
Session: Poster session 09
92P - Discovery of novel AXL and MER inhibitors as potential anticancer and immune modulator drugs
Presenter: Hsing-Pang Hsieh
Session: Poster session 09
93P - Transcriptome changes of immune cells across chemotherapy of triple-negative breast cancer
Presenter: Tatiana Gerashchenko
Session: Poster session 09
509P - Spatial analysis of tumor-associated macrophages within the tumor microenvironment of primary tumors and matched brain metastases
Presenter: Markus Kleinberger
Session: Poster session 09
510P - CD47 regulates cellular and metabolic plasticity in glioblastoma
Presenter: Ruhi Polara
Session: Poster session 09
511P - Immunodisruptive conditions and glioma diagnosis: 24-year retrospective study of an under-recognized scenario
Presenter: Santiago Cabezas-Camarero
Session: Poster session 09
512P - Heterozygous germline Fanconi anemia-related gene mutations increase susceptibility to central nervous system germ cell tumors
Presenter: Guangyu Wang
Session: Poster session 09
513P - Cyclin pathway in oligodendrogliomas IDH mut and 1p/19q codeleted
Presenter: Maria Angeles Vaz Salgado
Session: Poster session 09