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Mitochondrial targeting drug delivery systems have made unprecedented progress in tumor treatment. Nevertheless, the stability of systemic circulation and the effectiveness of tumor accumulation are the basis for achieving tumor subcellular targeting. This study aims to overcome the biological barrier while improving the mitochondria-targeted effect of nanoparticles based on natural polysaccharides. Novel polysaccharide-based nanoparticles, with tumor microenvironment-responsive charge-reversal and mitochondrial targeting abilities, wer