Hyaluronic acid drug-loaded nanomicelle

A targeted delivery system co-loading lactate oxidase and copper-doped carbon dots that enhances cuproptosis and activates antitumor immunity through lactate metabolism regulation.

Zhang, Hui · Xu, Zhu · Wang, Jingchun · Yikai, Ma · Rong, Shengzhong · Yuting, Lu · Jin, Yingxue

Materials Today Bio 2026

Specifications

Clinical response rate of α-PD-L1

{'zh': '10%-30%', 'en': '10%-30%'}

Laser wavelength

{'zh': '808', 'en': '808'} nm

Advantages

Lactate clearance

LOX efficiently clears lactate and elevates pH, blocking the HIF-1α/PD-L1 pathway to reverse immunosuppression.

Enhanced cuproptosis

It also generates H2O2 in situ to provide substrates for Cu-mediated Fenton-like reactions, enhancing cuproptosis.

Immune microenvironment remodeling

Promotes dendritic cell maturation and drives M2-type macrophage polarization toward the M1 phenotype, remodeling the antitumor immune microenvironment.

Abscopal effect

Combined with 808 nm laser and α-PD-L1, significantly inhibits primary and distant tumor growth in CT26 tumor-bearing mouse models.

Applications

• Combination cancer immunotherapy：Combines α-PD-L1 with lactate metabolism regulation and cuproptosis to enhance immunotherapy efficacy.
• Targeted nanodelivery：Achieves tumor targeting via specific binding between HA and CD44 receptors, improving drug delivery efficiency.
• Tumor microenvironment modulation：Clears lactate, elevates pH, and generates H2O2 to modulate the TME and enhance cuproptosis and immune activation.
• Immune checkpoint sensitization：Reverses immunosuppression by blocking the HIF-1α/PD-L1 pathway, sensitizing tumors to immune checkpoint blockade.