Dual-targeted delivery of paclitaxel and indocyanine green with aptamer-modified ferritin for synergetic chemo-phototherapy

Abstract

The combination of phototherapy and chemotherapy has become attractive and effective cancer treatment. However, the accurate delivery of both chemo-phototherapy drugs to the target site as well as the development of high-efficient phototherapy and chemotherapy drugs remain major challenges. In this study, indocyanine green (ICG) and paclitaxel (PTX)-loaded aptamer ferritin (HAS1411-PTX-ICG) was developed as a biocompatible nanoplatform for combined chemo/photothermal/photodynamic (PTT/PDT) therapy that was safe and highly effective against tumors. HAS1411 was prepared by coupling aptamer AS1411 to the surface of human H chain ferritin (HFtn) by the carbon diimide method to further enhance the targeting of HFtn. Both ICG and PTX were effectively encapsulated in the HAS1411 by incubation at 60 ℃. Moreover, under near-infrared (NIR) light irradiation, HAS1411 enhanced the photothermal effect and cell internalization of ICG, as well as the production of reactive oxygen species in cancer cells. HAS1411-PTX-ICG displayed effective cytotoxicity and a significant tumor spheroids inhibitory effect owning to the improved internalization of PTX and ICG mediated by TfR1 and nucleolin dual receptors. Co-loaded PTX combined with ICG can produce chemo/PTT/PDT under near-infrared (NIR) light irradiation, enhancing the anti-tumor effect. The dual-targeting HAS1411 nanocarrier developed in this study can be a promising delivery system for cancer therapy and the fabricated HAS1411-PTX-ICG possesses potential application in chemo-phototherapy.