Poly(2-oxazolines) as Precision Nanocarriers in Triple-Negative Breast Cancer: Advancing Targeted Chemotherapy Through Polymeric Innovation.

Abstract

Introduction: Poly(2-ethyl-2-oxazoline) (POx) has emerged as a highly promising drug delivery polymer due to its biocompatibility, stealth-like behavior, and versatile functionalization options. POx-based nanocarriers offer significant advantages for targeted drug delivery in oncology, particularly for challenging tumors such as triple-negative breast cancer (TNBC).

Methods: Recent literature from 2015 to 2025 on the synthesis, characterization, and biological applications of POx-based nanocarriers was systematically reviewed. Emphasis was placed on drug conjugation techniques, in vitro and in vivo performance, and computational studies that inform design optimization.

Results: POx micelles and hybrid systems demonstrate improved encapsulation efficiency, reduced off-target toxicity, and sustained drug release, achieving effective tumor targeting via the enhanced permeability and retention (EPR) effect. Notably, POx micelles loaded with β-elemene exhibit dual pH/GSH-responsive behavior with >92% encapsulation efficiency. Computational modeling has guided micelle design and predicted critical drug-polymer interactions.

Discussion: The structural flexibility of POx enables the engineering of dual-drug carriers and theranostic platforms. Clinical translation is progressing, although challenges remain regarding large-scale synthesis and regulatory standardization. Integration of POx-based systems into combination therapies and personalized oncology strategies represents a promising path forward, supported by encouraging preclinical results.

Conclusion: POx nanocarriers exhibit strong translational potential for TNBC due to high drug loading, biocompatibility, and tunable release profiles. They provide enhanced tumor accumulation, active targeting, and the ability to overcome multidrug resistance, supported by favorable pharmacokinetics and computational design insights. Remaining challenges include large-scale production, long-term safety assessment, and regulatory approval. Future directions focus on dual- and stimuli-responsive systems and their integration into precision oncology to accelerate clinical translation.