Thermosensitive Polymeric Nanoparticles for Drug Co-Encapsulation and Breast Cancer Treatment

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Ductal carcinoma in situ (DCIS) requires effective local management strategies.
• Intraductal drug delivery offers advantages in target site retention, efficacy, and reduced systemic exposure.

Purpose of the Study:

• To develop and evaluate a poly(N-isopropyl acrylamide, pNIPAM) nanoparticle system for intraductal delivery of piplartine and a MAPKAP Kinase 2 inhibitor (YARA).
• To enhance nanoparticle targeting to the tumor microenvironment using a collagen-binding peptide (SILY).

Main Methods:

• Characterization of pNIPAM nanoparticles including diameter, zeta potential, drug loading, and release kinetics.
• In vitro cytotoxicity assessment using 2D cell cultures and 3D spheroids.
• In vivo efficacy evaluation in a rat chemical carcinogenesis model.

Main Results:

• Nanoparticle delivery significantly reduced the IC50 of piplartine (4.9-fold) and enhanced efficacy when combined with YARA (~15-fold).
• Intraductal nanoparticle treatment decreased in vivo tumor incidence by 5.2-fold.
• High drug concentration in mammary glands (35.3 μg/mL) with minimal plasma levels (0.7 μg/mL) confirmed targeted retention.

Conclusions:

• The developed SILY-functionalized pNIPAM nanocarrier system demonstrates effective local delivery and retention for DCIS treatment.
• This nanocarrier approach shows significant potential for reducing tumor development with minimized systemic toxicity.