Photothermally activatable PDA immune nanomedicine combined with PD-L1 checkpoint blockade for antimetastatic cancer photoimmunotherapy

Apr 8, 2020Journal of materials chemistry. B

Light-activated immune nanomedicine combined with PD-L1 checkpoint blockade for preventing cancer spread using photoimmunotherapy

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Abstract

PDA-PEG-R848-CD nanoparticles could significantly improve therapeutic efficiency against tumors.

Photothermal therapy (PTT) combined with immune checkpoint blockade (ICB) may eliminate primary tumors and prevent metastasis to the lungs and liver.
The designed nanoparticles incorporate a toll-like receptor 7 (TLR7) agonist and a fluorescent agent to enhance treatment efficacy.
PTT under near-infrared laser irradiation can destroy 4T1 breast tumors while generating tumor-associated antigens.
The treatment may trigger a strong antitumor immune response by releasing R848 during PTT.
The synergistic therapy could completely inhibit the growth of untreated distant tumors by stimulating immune cell infiltration.

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Photothermal therapy (PTT) has shown promising potential and bright prospects in damaging primary tumors; however, it is limited to metastatic and recrudescent tumors as PTT requires straightforward light irradiation. Moreover, metastatic and recrudescent tumor immunosuppression due to host T-cell antitumor activity is dramatically impeded because of programmed cell death 1 ligand (PD-L1) and programmed cell death receptor 1 (PD-1) pathways and immune checkpoint blockade (ICB) therapy. In this work, we demonstrate that PTT combined with ICB could not only eliminate primary tumors, but also prevent tumor metastasis to the lungs/liver. In particular, we have designed immunoadjuvant nanomedicine carriers on the basis of polydopamine (PDA) simultaneously loaded with resiquimod (R848)-a kind of toll-like receptor 7 (TLR7) agonist-and carbon dots (CDs)-a fluorescent agent. This nanomedicine is defined as PDA-PEG-R848-CD nanoparticle (NP). The multitasking PDA-PEG-R848-CD NPs can destroy 4T1 breast tumors by PTT under near-infrared laser irradiation in addition to generating tumor-associated antigens. Moreover, the PTT effect triggered the release of R848, thereby inducing a strong antitumor immune response. Meanwhile, this synergistic therapy also shows the abscopal effects by completely inhibiting the growth of untreated distant tumors by effectively triggering the tumors infiltrated by CD3/CD8. Such findings suggest that PDA-PEG-R848-CD NPs could significantly potentiate the systemic therapeutic efficiency of PD-L1 checkpoint blockade therapy by activating both innate and adaptive immune systems in the body.

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Photothermally activatable PDA immune nanomedicine combined with PD-L1 checkpoint blockade for antimetastatic cancer photoimmunotherapy

Abstract

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