To improve the selective delivery of cisplatin (Cis) to cancer cells, we report and establish the significance of active, targeting drug delivery nanosystems for efficient treatment of lung cancer. Specifically, pH-responsive nano-sized zeolitic imidazolate framework (nZIF-90) was synthesized, post-synthetically modified with an Arg-Gly-Asp peptide motif (RGD@nZIF-90), a known cancer cell homing peptide, and loaded with a large amount of Cis (RGD@Cis⊂nZIF-90). RGD@Cis⊂nZIF-90 was shown to be highly stable under physiological conditions (pH = 7.4) with framework dissociation occurring under slightly acidic conditions (pH = 5.0)-conditions relevant to tumor cells-from which 90% of the encapsulated Cis was released in a sustained manner. In vitro assays demonstrated that RGD@Cis⊂nZIF-90 achieved significantly better cytotoxicity (65% at 6.25 μg ml-1) and selectivity (selectivity index = 4.18 after 48 h of treatment) against adenocarcinoma alveolar epithelial cancer cells (A549) when compared with the unmodified Cis⊂nZIF-90 (22%). Cellular uptake using A549 cells indicated that RGD@Cis⊂nZIF-90 was rapidly internalized leading to significant cell death. After successfully realizing this nanocarrier system, we demonstrated its efficacy in transporting and delivering Cis to cancer cells.