DNA-toxin anticancer drugs target nuclear DNA or its associated enzymes to elicit their pharmaceutical effects, but cancer cells have not only membrane-associated but also many intracellular drug-resistance mechanisms that limit their nuclear localization. Thus, delivering such drugs directly to the nucleus would bypass the drug-resistance barriers. The cationic polymer poly(L-lysine) (PLL) is capable of nuclear localization and may be used as a drug carrier for nuclear drug delivery, but its cationic charges make it toxic and cause problems in in-vivo applications. Herein, PLL is used to demonstrate a pH-triggered charge-reversal carrier to solve this problem. PLL's primary amines are amidized as acid-labile β-carboxylic amides (PLL/amide). The negatively charged PLL/amide has a very low toxicity and low interaction with cells and, therefore, may be used in vivo. But once in cancer cells' acidic lysosomes, the acid-labile amides hydrolyze into primary amines. The regenerated PLL escapes from the lysosomes and traverses into the nucleus. A cancer-cell targeted nuclear-localization polymer–drug conjugate has, thereby, been developed by introducing folic-acid targeting groups and an anticancer drug camptothecin (CPT) to PLL/amide (FA-PLL/amide-CPT). The conjugate efficiently enters folate-receptor overexpressing cancer cells and traverses to their nuclei. The CPT conjugated to the carrier by intracellular cleavable disulfide bonds shows much improved cytotoxicity.