Journal
ACS NANO
Volume 14, Issue 4, Pages 3991-4006Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.9b07984
Keywords
amphiphilic nanogapped gold nanoparticles; photoacoustic imaging; second NIR window; polymeric prodrug; chemo-immunotherapy
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Funding
- National Natural Science Foundation of China [21635002, 21874024, 21674116]
- Program for Changjiang Scholars [IRT15R11]
- Innovative Research Team in University [IRT15R11]
- Youth Innovation Promotion Association CAS [2018257]
- Natural Science Foundation of Fujian Province of China [2017Y0058]
- Intramural Research Program (IRP), National Institute of Biomedical Imaging and Bioengineering (NIBIB)
- National Institutes of Health (NIH)
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We developed dual biologically responsive nanogapped gold nanoparticle vesicles loaded with immune inhibitor and carrying an anticancer polymeric prodrug for synergistic concurrent chemo-immunotherapy against primary and metastatic tumors, along with guided cargo release by photoacoustic (PA) imaging in the second near-infrared (NIR-II) window. The responsive vesicle was prepared by self-assembly of nanogapped gold nanoparticles (AuNNPs) grafted with poly(ethylene glycol) (PEG) and dual pH/GSH-responsive polyprodug poly(SN-38-co-4-vinylpyridine) (termed AuNNP@PEG/PSN38VP), showing intense PA signal in the NIR-II window. The effect of the rigidity of hydrophobic polymer PSN38VP on the assembled structures and the formation mechanism of AuNNP@SN38 Ve were elucidated by computational simulations. The immune inhibitor BLZ-945 was encapsulated into the vesicles, resulting in pH-responsive release of BLZ-945 for targeted immunotherapy, followed by the dissociation of the vesicles into single AuNNP@PEG/PSN38VP. The hydrophilic AuNNP@ PEG/PSN38VP nanoparticles could penetrate deep into the tumor tissues and release the anticancer drug SN38 under the reductive environment. A PA signal in the NIR-II window in the deep tumor region was obtained. The BLZ-945-loaded vesicle enabled enhanced PA imaging-guided concurrent chemo-immunotherapy efficacy, inhibiting the growth of both primary tumors and metastatic tumors.
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