Dandelion-Like Tailorable Nanoparticles for Tumor Microenvironment Modulation.

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Tumor-associated macrophages (TAMs) are crucial in tumor progression, making them therapeutic targets.
• Current nanosized therapies face challenges in penetrating dense tumor microenvironments due to high interstitial fluid pressure and extracellular matrix.
• Modulating TAM polarization offers a promising strategy for cancer treatment.

Purpose of the Study:

• To design an acid-triggered, size-changeable nanoparticle (Apt@(DGL-ZA) NPs) for improved tumor penetration and therapeutic delivery.
• To enhance the distribution, extravasation, and penetration of nanotherapies within solid tumors.
• To develop a novel strategy for modulating TAMs and inducing tumor autophagy for effective cancer treatment.

Main Methods:

• Dendrigraft poly-L-lysines (DGLs) were crosslinked with an acid-sensitive linker and loaded with zoledronic acid (ZA).
• A Tenascin-C targeting aptamer (GBI-10) was conjugated to the DGL/ZA nanoparticles (NPs) to create Apt@(DGL-ZA) NPs.
• The nanoparticles' penetration, macrophage regulation, autophagy induction, and antitumor efficacy were evaluated in vitro and in vivo.

Main Results:

• Apt@(DGL-ZA) NPs demonstrated enhanced penetration in 3D breast cancer spheroids and in vivo tumor tissues.
• The nanoparticles effectively regulated macrophages and induced tumor autophagy.
• Significant in vivo antitumor efficacy was observed, highlighting the therapeutic potential.

Conclusions:

• Acid-triggered, size-changeable nanoparticles show promise for overcoming tumor penetration barriers.
• This nanoparticle system effectively targets TAMs, enhances tumor autophagy, and exhibits potent antitumor activity.
• The developed Apt@(DGL-ZA) NPs represent a significant advancement in cancer therapeutic strategies.