Dual-Targeted Assembled Nanodrugs for Near-Infrared Photothermal Immunotherapy of Triple-Negative Breast Cancer

Area of Science:

• Biomaterials Science
• Nanomedicine
• Cancer Therapy

Background:

• Triple-negative breast cancer (TNBC) presents a significant clinical challenge due to its aggressive nature, high recurrence rates, and limited treatment options.
• Photothermal therapy (PTT) is a promising minimally invasive cancer treatment, but its efficacy relies heavily on the performance of photothermal agents.
• There is a critical need for advanced photothermal drugs with enhanced tumor targeting, high conversion efficiency, and improved biosafety for TNBC treatment.

Purpose of the Study:

• To develop and evaluate a novel tumor-targeted photothermal agent for enhanced triple-negative breast cancer (TNBC) therapy.
• To investigate the agent's photothermal conversion efficiency, tumor-targeting capabilities, and biosafety.
• To assess the agent's impact on the tumor immune microenvironment and its potential to inhibit TNBC metastasis and recurrence.

Main Methods:

• Biomolecular assembly of biliverdin manganese complexes (MnBV) with amphiphilic phospholipid-polymer conjugates (DSPE-PEG and DSPE-PEG-cKNGRE) to create a near-infrared (NIR) absorbing photothermal agent.
• Characterization of the assembled agent for size, stability, and photothermal conversion efficiency.
• In vivo evaluation in a 4T1 TNBC mouse model to assess tumor targeting, drug enrichment, and therapeutic efficacy, including immune response modulation.

Main Results:

• The developed photothermal agent demonstrated uniform size, good stability, and efficient photothermal conversion.
• The agent exhibited significant tumor dual-targeting capabilities and drug enrichment in the 4T1 TNBC mouse model.
• Photothermal therapy using the agent stimulated dendritic cell maturation, enhanced T lymphocyte infiltration, and effectively inhibited tumor metastasis and recurrence, reshaping the immune microenvironment.

Conclusions:

• The novel biomolecularly assembled photothermal agent shows significant potential as an innovative therapeutic strategy for triple-negative breast cancer.
• This approach offers precise, targeted, and safe treatment, addressing the limitations of current therapies for aggressive malignancies.
• The agent's ability to modulate the immune microenvironment presents a new avenue for combating TNBC metastasis and recurrence.