# Self-passivated bilayer black phosphorus QDs based multifunctional nanoparticles for tumor immune reprogramming

## TL;DR

Researchers developed a safe and effective nanoplatform using self-passivated black phosphorus quantum dots to enhance tumor treatment and imaging.

## Contribution

The study introduces a novel nanoplatform (BD3PP) combining photothermal, photodynamic, and targeted therapies for tumor immune reprogramming.

## Key findings

- Self-passivated bilayer BPQDs showed superior photothermal and photodynamic therapy efficiency compared to non-passivated forms.
- BD3PP induced immunogenic cell death and promoted M1 macrophage polarization to remodel the tumor microenvironment.
- DFT calculations confirmed BPQD degradation into biocompatible phosphoric acid, ensuring biosafety.

## Abstract

It is important yet challenging to enhance immunotherapy responses using biosafe agents due to the immunosuppressive tumor microenvironment. To address this challenge, BD3PP was constructed by encapsulating black phosphorus quantum dots (BPQDs), a synthesized thioredoxin reductase inhibitor 3c, and Dir (the fluorescent dye) into PLGA nanoparticles, followed by conjugation with a PDL1 antagonist for synergistic multimodal therapy and imaging. The mechanism and efficiency of BD3PP were investigated through density functional theory (DFT) calculations, molecular docking, and in vitro and in vivo experiments. The PDL1 antagonist served as a targeting moiety that binds PDL1 on the tumor cell surface, enabling the controlled intracellular release of the three therapeutic agents. Self-passivated bilayer BPQDs converted optical energy into heat for photothermal therapy and generated singlet oxygen (1O2) from O2 for type II photodynamic therapy, showing far superior to non-passivated bilayer BPQDs or bulk BP. Meanwhile, 3c selectively inhibited thioredoxin reductase, leading to the production of ·O2‐ and H2O2. These effects synergistically induced immunogenic cell death (ICD), promoted macrophage polarization toward the M1 phenotype, and remodeled the tumor microenvironment to facilitate tumor clearance. The near-infrared fluorescent dye Dir enabled real-time imaging both in vitro and in vivo. DFT calculation revealed that BPQDs were ultimately degraded into biocompatible phosphoric acid. Along with the other biocompatible components in BD3PP, biosafety was guaranteed. This research introduces an efficient and biosafe nanoplatform based on self-passivated bilayer BPQDs, which exhibits prolonged blood circulation and enhanced multimodal real-time photothermal and near-infrared imaging. Importantly, this nanoplatform enables integrated photothermal, photodynamic, and targeted therapies, demonstrating promising potential for anti-tumor preclinical and clinical applications.

Image 1

•Ultrasmall, homogeneous, self-passivated bilayer BPQDs were successfully prepared.•The PDT mechanism and the biodegradation of BPQDs were firstly investigated by DFT.•BD3PP induced ICD to remodel the tumor microenvironment to clear tumors.•BD3PP prolonged blood circulation, multimode imaging and therapy efficiency.

Ultrasmall, homogeneous, self-passivated bilayer BPQDs were successfully prepared.

The PDT mechanism and the biodegradation of BPQDs were firstly investigated by DFT.

BD3PP induced ICD to remodel the tumor microenvironment to clear tumors.

BD3PP prolonged blood circulation, multimode imaging and therapy efficiency.