A layered target-release nanoparticle system for normalizing the lung cancer microenvironment and enhancing antitumor...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Solid tumors exhibit abnormal vasculature and dense collagen, leading to high interstitial pressure that hinders nanoparticle drug delivery.
• Tumor microenvironment normalization is a key strategy to improve therapeutic penetration.
• Developing advanced drug delivery systems is crucial for overcoming these barriers in lung cancer.

Purpose of the Study:

• To engineer a pH-responsive bilayer nanoplatform for sequential drug delivery in lung cancer.
• To investigate the platform's ability to modulate the tumor microenvironment and deliver a targeted chemotherapeutic.
• To enhance the efficacy of nanoparticle-based therapeutics in solid tumors.

Main Methods:

• A bilayer lipid nanoparticle system (LT@TPL-NPs) was designed, encapsulating triptolide (TPL) and ligustrazine (LT).
• The nanoparticles featured folic acid modification for targeting and pH-sensitive lipids for controlled release.
• In vitro assays assessed NP characterization, pH-responsive release, and cellular uptake.

Main Results:

• The nanoplatform demonstrated sequential release of LT followed by TPL-NPs in acidic tumor environments.
• Ligustrazine (LT) effectively normalized the tumor microenvironment, reducing interstitial pressure and increasing nanoparticle penetration.
• Folic acid-modified TPL-loaded nanoparticles showed efficient cellular uptake and intracellular delivery in lung cancer models.

Conclusions:

• The developed pH-responsive nanoplatform enables spatiotemporally controlled release of therapeutic agents.
• This strategy synergistically combines microenvironment remodeling with targeted tumor cell cytotoxicity.
• The approach shows promise for overcoming solid tumor delivery barriers and warrants further preclinical evaluation.