Photoacoustic-immune therapy with a multi-purpose black phosphorus-based nanoparticle
- PDF / 4,880,789 Bytes
- 13 Pages / 612 x 808 pts Page_size
- 25 Downloads / 133 Views
y Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China 2 Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China § Fanchu Zeng and Huan Qin contributed equally to this work. © Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020 Received: 23 June 2020 / Revised: 28 July 2020 / Accepted: 1 August 2020
ABSTRACT Effective therapeutic strategies to precisely eradicate primary tumors with minimal side effects on normal tissue, inhibit metastases, and prevent tumor relapses, are the ultimate goals in the battle against cancer. We report a novel therapeutic strategy that combines adjuvant black phosphorus nanoparticle-based photoacoustic (PA) therapy with checkpoint-blockade immunotherapy. With the mitochondria targeting nanoparticle, PA therapy can achieve localized mechanical damage of mitochondria via PA cavitation and thus achieve precise eradication of the primary tumor. More importantly, PA therapy can generate tumor-associated antigens via the presence of the R848-containing nanoparticles as an adjuvant to promote strong antitumor immune responses. When combined with the checkpoint-blockade using anti-cytotoxic T-lymphocyte antigen-4, the generated immunological responses will further promote the infiltrating CD8 and CD4 T-cells to increase the CD8/Foxp3 T-cell ratio to inhibit the growth of distant tumors beyond the direct impact range of the PA therapy. Furthermore, the number of memory T cells detected in the spleen is increased, and these cells inhibit tumor recurrence. This proposed strategy offers precise eradication of the primary tumor and can induce long-term tumor-specific immunity.
KEYWORDS photoacoustic therapy, mitochondrial targeting, black phosphorus, immunotherapy, checkpoint blockade
1
Introduction
Developing effective therapeutic strategies to precisely eradicate primary tumors, inhibit metastases, and prevent tumor relapses, without side effects are the ultimate objectives in the battle against cancer. The current gold-standard cancer treatment approaches are surgery, chemotherapy, and radiotherapy, but none can completely achieve this goal [1]. Cancer immunotherapy is a very popular approach that stimulates the innate and adaptive immune systems against tumors and has been progressing rapidly, showing tremendous promise as a next generation tool for cancer treatment strategy [1, 2]. An important immune resistance mechanism involves immune inhibition (immune checkpoints) that normally mediates immune tolerance and tumor escape [2–6]. Checkpoint blockades are a corresponding monotherapy that will only succeed in the setting of a preexisting antitumor immune response [1, 4]. Therefore, to expand the efficacy of immunotherapy, a checkpoint blockade [4, 5, 7, 8] was combined with other traditional clinical therapies to induce de novo antitumor immune responses [9]. Chemotherapy and radia
Data Loading...
