Abstract
The resonance energy transfer (RET) between an excited fluorescent probe molecule and a plasmonic nanoparticle (AuNP) has been investigated to evaluate the effect of protein molecules on the RET efficiency. We have found that the energy transfer to a functionalized AuNP can be modulated by a sub-monolayer film of programmed death-ligand 1 (PD-L1) protein. The interactions of PD-L1 with AuNP@Cit involve incorporation of the protein in AuNP shell and formation of a submonolayer adsorption film with voids enabling gated surface plasmon resonance energy transfer (SPRET). A model of the gated-RET system based on the protein size, estimated using Fisher–Polikarpov–Craievich density approximation, has been developed and can be utilized for other proteins, with minimum data requirement, as well. The value of the equilibrium constant KL determined for the Langmuir isotherm is high: KL = 1.27 × 108 M−1, enabling highly sensitive control of the gated-RET by PD-L1. Thus, with the gated-RET technique, one can determine PD-L1 within the dynamic range, extending from 1.2 to 50 nM. Moreover, we have found that the Gibbs free energy for PD-L1 binding to AuNP@Cit is −46.26 kJ/mol (−11.05 kcal/mol), indicating a strong adsorption with supramolecular interactions. The proposed gated-RET system, with the fluorescence intensity of the fluorophore probe molecule modulated by plasmonic quenching with AuNP and shielding of energy transfer by the adsorbed PD-L1 can be further developed for determination of PD-L1 in pharmaceutical formulations for immune checkpoint control in cancer therapy.
Highlights
Significant progress, achieved in the last two decades, in understanding processes that enable cancer to grow and metastasize freely, while evading the immune response of the host, has largely been associated with exploring pathways controlling the apoptosis and the immune checkpoints
We have focused on the interactions of clinically relevant protein programmed death-ligand 1 (PD-L1), which is a ligand to the receptor PD-1, with a functionalized gold nanoparticle (AuNP)
We have demonstrated that the resonance energy transfer (RET) from a fluorescein isothiocyanate (FITC) fluorescent dye to citrate-capped gold nanoparticles (AuNP@Cit) can be modulated by a gating sub-monolayer film of cytochrome c (Cyt c) [19], bovine serum albumin (BSA) [19], and survivin (Sur) [20] proteins surrounding AuNP@Cit
Summary
Significant progress, achieved in the last two decades, in understanding processes that enable cancer to grow and metastasize freely, while evading the immune response of the host, has largely been associated with exploring pathways controlling the apoptosis (e.g., with apoptosis inhibitor proteins, AIP) and the immune checkpoints (e.g., with programmed death protein 1, PD-1). We have found that PD-L1, at low concentrations has the ability to partially block AuNP surface and to modulate the resonance energy transfer (RET) from an excited fluorophore probe molecule to the surface plasmons of AuNP This property can be utilized for sensitive detection of PD-L1 using gated-RET technique, we have recently developed [19,20]. PD-L1 is the third member of the B7 family together with B7-1 and B7-2 [25] and it is a ligand for the programmed cell death protein 1 (PD-1), regulating the immune response by suppressing inflammatory activity It was discovered in 1992, on T cells, by Honjo and his group [26]. A generalized model of the gated-RET for any protein that binds to a functionalized AuNP has been developed based on the average protein density calculated using Fisher–Polikarpov–Craievich equation [39] which enables estimation of the monolayer surface coverage γmax of a protein on AuNPs
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