Journal
NANO TODAY
Volume 43, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.nantod.2022.101417
Keywords
Switchable size-charge; Enhanced tumor penetration; Deep immune cell recruitment; Synergetic sono-immunotherapy
Categories
Funding
- Major State Basic Research Development Program of China [2017YFA0205201]
- National Natural Science Foundation of China (NSFC) [81901876, 81925019, 81801817, 81603015, U1705281]
- Fundamental Research Funds for the Central Universities [20720190088, 20720200019]
- Program for New Century Excellent Talents in University, China [NCET-13-0502]
- China Postdoctoral Science Foundation [2021M702739, 2021M702738]
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This study engineered an anti-programmed death ligand 1 peptide inhibitor (APP) to act in the inner core of unimolecular polymers, which could form size-charge switchable nanomicelles in an acidic tumor microenvironment. Under fluorescence/photoacoustic imaging guidance, these nanomicelles could control the exposure of APP and induce reactive oxygen species (ROS) for immune T-cell recruitment and activation in deep solid tumors.
Immune checkpoint inhibitor-based immunotherapy has been the most promising method for treating cancer patients. In this study, an anti-programmed death ligand 1 peptide inhibitor (APP) was engineered to act in the inner core of unimolecular polymers (Dex-PCR780-b-P(DPA-co-APP). The APP polymers had the capability of forming nano-micelles (PCR780-APP NMs) via self-assembly and featured controlled exposure in an acidic microenvironment while maintaining APP original bioactivity. Notably, in an acid tumor microenvironment, the PCR780-APP NMs (~ 121.1 nm, 2.3 mV) quickly switched into ultrasmall and positively charged PCR780-APP unimolecular micelles (PCR780-APP UMs; ~ 24.1 nm, 19.6 mV) with ultrastability, a narrow polydispersity index, and great fluorescence/photoacoustic (FL/PA) linearity due to its unique and definite unimolecular structure. Based on these advantages, under FL/PA imaging guidance, size-charge switchable PCR780-APP NMs could control exposure of APP and when combined with ultrasound, induce specific-dosage reactive oxygen species (ROS) that facilitates abundant immune T-cell recruitment and activation in deep solid tumors.(c) 2022 Elsevier Ltd. All rights reserved.
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