Multifunctional delivery strategies and nanoplatforms of SN-38 in cancer therapeutics

SN-38 or 7-ethyl-10-hydroxycamptothecin is the active metabolite of irinotecan, a widely used chemotherapeutic agent for the treatment of colorectal, pancreatic, lung, breast, gastric, esophageal, hepatocellular, ovarian, brain, leukemia, and lymphoma malignancies. SN-38's antitumoral effect is 100 to 1000 times more potent than that of irinotecan. However, its clinical application is hindered by its poor solubility and chemical instability. To circumvent these challenges and avoid systemic toxicities, such as myelosuppression and diarrhea, several SN-38 delivery systems have been explored. In that regard, formulations based on targeted, controlled and tumor-responsive release of SN-38 have demonstrated to enhance its antitumoral effects and reduce the associated systemic toxicities by limiting the pharmacological activity to the desired tumor location. To this end, prodrugs, conjugates, nanoparticles, dendrimers, or lipid-based strategies for SN-38 delivery have been used. Most recently, multifunctional approaches have emerged as an attractive alternative to develop SN-38 delivery systems, combining several strategies in a single formulation, i.e., encapsulating nanocarriers, tumor-targeting ligands, stimuli-responsive elements, optimal linkers, drug combinations or bioimaging agents. Despite their therapeutic advantages, multifunctional delivery systems often face challenges concerning their clinical translation compared to conventional therapies, such as biocompatibility, scalability and cost-effectiveness issues. The aim of this work is to review the most recent progress that has been made in the development and assessment of multifunctional delivery systems for cancer treatment.