Nanoparticle-based strategies as emerging tools for oral chemotherapy of colorectal cancer

Colorectal cancer (CRC) chemotherapy remains clinically challenging due to the emergence of drug resistance, off-target toxicity, and suboptimal patient compliance, underscoring the need for innovative, patient-centric delivery systems specially designed for targeted CRC therapy. Oral delivery of chemotherapeutic drugs offers a potential solution, with the benefits of enhanced treatment adherence and patient compliance. However, conventional oral chemotherapy is significantly hindered by multiple physiological, chemical, microbial, and tumor microenvironment-associated barriers within the GIT of CRC patients. In this regard, nanoparticle-based drug delivery systems have emerged as a promising tool to overcome the challenges associated with the distal colon's anatomical position when delivering chemotherapeutic drugs via the oral route, while simultaneously reducing the risk of non-specific gastrointestinal toxicity. This review uniquely integrates the gastrointestinal and tumor microenvironment barriers encountered in oral chemotherapy for CRC and establishes the rationale for using nanoparticle-based drug delivery and for developing suitable nanoformulations to overcome these barriers and impart therapeutic effects. Moreover, it provides a comprehensive overview of recent advancements in this domain, with particular emphasis on current translational constraints and prospective strategies towards further clinical translation.