Biodegradable mesoporous nanocomposites with dual-targeting function for enhanced anti-tumor therapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Research

Background:

• Tumor-associated macrophages (TAMs) are key regulators of tumor progression, often adopting an M2-like phenotype that favors cancer development.
• The tumor microenvironment (TME) plays a critical role in cancer progression, making dual targeting of cancer cells and the TME a significant area in tumor immunotherapy.

Purpose of the Study:

• To develop pH-sensitive mesoporous calcium silicate nanocomposites (MCNs) for combined photothermal therapy (PTT) and photodynamic therapy (PDT).
• To engineer MCNs with mannose and hyaluronic acid for targeted delivery to TAMs and tumor cells.
• To evaluate the efficacy of the nanoplatform in inducing cancer cell apoptosis in vitro and in vivo.

Main Methods:

• Fabrication of pH-sensitive mesoporous calcium silicate nanocomposites (MCNs) encapsulated with indocyanine green (ICG).
• Grafting of mannose and hyaluronic acid onto MCNs for targeted cell recognition.
• Application of 808 nm near-infrared (NIR) light to trigger PTT and PDT.
• In vitro and in vivo assessment of MCNs' efficacy in targeting, apoptosis induction, hyperthermia, and singlet oxygen generation.

Main Results:

• The developed MCNs demonstrated pH-sensitivity and effective encapsulation of ICG.
• Mannose and hyaluronic acid functionalization enabled specific targeting of TAMs and tumor cells.
• NIR irradiation of ICG-loaded MCNs induced significant hyperthermia and intracellular singlet oxygen generation.
• The nanoplatform effectively promoted cancer cell apoptosis both in vitro and in vivo.

Conclusions:

• The novel nanoplatform offers a promising strategy for dual PTT and PDT, targeting both cancer cells and TAMs.
• The pH-sensitive MCNs facilitate enhanced tumor treatment by combining hyperthermia and photodynamic effects.
• This approach holds potential for improving tumor immunotherapy and facilitating the delivery of chemotherapeutic agents to the TME.