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Introduction: The utilization of polymeric nanoparticles, as drug payloads, has been extensively prevailed in cancer therapy. However, the precise distribution of these nanocarriers is restrained by various physiological and cellular obstacles. Nanoparticles must avoid nonspecific interactions with healthy cells and compartments to circumvent these barriers. Since interactions of nanoparticles are mainly dependent on surface properties of nanoparticles, efficient control on surface constituents is necessary for the determination of nanoparticles' fate in the body.

Areas Covered: In this review, the surface-modified polymeric nanoparticles and their utilization in cancer treatment were elaborated. First, the interaction of nanoparticles with numerous barriers was highlighted. Second, different strategies to overcome these obstacles were described. Third, some inspiring examples of surface-modified nanoparticles were presented. Later, fabrication and characterization methods of surface-modified nanoparticles were discussed. Finally, the applications of these nanoparticles in different routes of treatments were explored.

Expert Opinion: Surface modification of anticancer drug-loaded polymeric nanoparticles can enhance the efficacy, selective targeting, and biodistribution of the anticancer drug at the tumor site.