Concurrent P-Selectin Targeting Nanoparticle Orchestrates Tumor-Immune Dynamics for Advanced Immunochemotherapy

Area of Science:

• Nanotechnology
• Cancer Biology
• Immunotherapy

Background:

• Current cancer therapies often fail to address the complex tumor microenvironment (TME).
• Targeting single mechanisms overlooks the intricate interactions within the TME.
• Developing novel strategies to simultaneously target cancer cells and immune cells is crucial for effective therapy.

Purpose of the Study:

• To introduce FINAL (Fucoidan-docetaxel Immunomodulatory Nanoparticles as an Antitumoral Lancer), a nanoplatform for simultaneous targeting of P-selectin-expressing cancer cells and tumor-associated macrophages (TAMs).
• To investigate the therapeutic potential of FINAL in reshaping the TME and enhancing cancer treatment outcomes.
• To evaluate the safety and efficacy of FINAL compared to conventional docetaxel formulations.

Main Methods:

• Surface-engineered nanoparticles (FINAL) were developed with fucoidan and docetaxel.
• P-selectin-mediated targeting was employed to engage cancer cells and TAMs.
• RNA-seq transcriptomic profiling was used to analyze molecular-level changes in tumor-immune dynamics.
• In vivo studies in triple-negative breast cancer (TNBC) models were conducted to assess therapeutic outcomes and toxicity.

Main Results:

• FINAL demonstrated dual-cell orchestration via P-selectin-mediated targeting, enhancing cellular uptake and disrupting tumor-TAM adhesion.
• Fucoidan's intrinsic bioactivities reduced cancer cell reactive oxygen species, promoted M1 macrophage polarization, and suppressed angiogenesis.
• Transcriptomic analysis revealed synergistic immune activation and repressed tumor progression signatures.
• In TNBC models, FINAL doubled survival duration, suppressed tumor growth, inhibited metastasis, and preserved bone marrow function.
• FINAL achieved significant therapeutic benefits with reduced systemic toxicity.

Conclusions:

• FINAL represents a versatile platform for P-selectin-expressing diseases, offering a next-generation immunochemotherapy approach.
• The system-level modulation of the TME by FINAL provides breakthrough therapeutic outcomes with improved safety.
• This nanoplatform shows broad translational potential across multiple cancer types for enhanced antitumor efficacy and reduced systemic toxicity.