Oxaliplatin (OXA) resistance remains the major obstacle to the successful
chemotherapy of
colorectal cancer (CRC). As a self-protection mechanism, autophagy may contribute to
tumor drug resistance, therefore autophagy suppression could be regarded as a possible treatment option in
chemotherapy.
Cancer cells, especially
drug-resistant
tumor cells, increase their demand for specific
amino acids by expanding exogenous supply and up-regulating de novo synthesis, to meet the needs for excessive proliferation. Therefore, it is possible to inhibit
cancer cell proliferation through pharmacologically blocking the entry of
amino acid into
cancer cells. SLC6A14 (ATB0,+) is an
essential amino acid transporter, that is often abnormally up-regulated in most
cancer cells. Herein, in this study, we designed
oxaliplatin/
berbamine-coloaded, ATB0,+-targeted nanoparticles ((O + B)@Trp-NPs) to therapeutically target SLC6A14 (ATB0,+) and inhibit
cancer proliferation. The (O + B)@Trp-NPs utilize the surface-modified
tryptophan to achieve SLC6A14-targeted delivery of
Berbamine (BBM), a compound that is found in a number of plants used in
traditional Chinese medicine, which could suppress autolysosome formation though impairing autophagosome-lysosome fusion. We verified the feasibility of this strategy to overcome the OXA resistance during
colorectal cancer treatment. The (O + B)@Trp-NPs significantly inhibited the proliferation and decreased the drug resistance of resistant
colorectal cancer cells. In vivo, (O + B)@Trp-NPs greatly suppressed the
tumor growth in
tumor-bearing mice, which is consistent with the in vitro data. This research offers a unique and promising chemotherapeutic treatment for
colorectal cancer.