Recent Progress of Crosslinking Strategies for Polymeric Micelles with Enhanced Drug Delivery in Cancer Therapy

Abstract

Background: The drug delivery by versatile types of self-assembled micelles for tumor treatment, which improved the diagnostic and therapeutic effectiveness, is advocated. However, despite the numerous advantages, applications of most micelle system have been retarded by low in vivo bio-stability which led to premature drug release and nonspecific tissue accumulation. To date, a range of chemistries has been introduced in intermolecular non-covalent/covalent crosslinking strategies for these dynamic nanostructures to produce robust functional nanoparticles with enhanced circulation stability and lower non-targeted organ toxicity. Objective: We focused on recent developments in crosslinking polymeric nanoparticles in cancer therapy. Methods: Types of chemistries used in the crosslinking strategies of the micelles are outlined and their enhanced drug delivery abilities are discussed. Results: We reviewed one hundred and nineteen papers and discussed in six aspect. More than 30 examples have been carefully discussed. Conclusion: Over the last decade, numerous of strategies for micelles crosslinking, such as disulfide coupling, free radical polymerization, physical interactions, chelation, and formation of microenvironment- responsive bonds, have been developed for enhancing micelles circulation stability, minimizing organ toxicity and achieving higher tumor targeting specificity. The application of these chemistries for micelle stabilizing might bring a new generation of versatile crosslinked micelles with enhanced therapeutic index and facilitate their further clinical translations.