Programmed-stimuli responsive carrier-free multidrug delivery system for highly efficient trimodal combination therapy

Programmed response, carrier-free, and multimodal therapy drug delivery systems (DDS) are promising solutions to multidirectional cytotoxic effects, inefficient antitumor, and severe side effects for cancer therapy. Here, three widely used clinical drugs, interferon a1b (IFNa1b), indocyanine green (ICG), and doxorubicin (DOX), were prepared into carrier-free DDS IFNa1b-ICG-DOX (IID) by a simple one-step method without additional any reagents. IID can achieve smart and programmed DDS by combining low pH and near-infrared (NIR) light stimuli-responsive controlled release. In pH = 7.4 environments, our IID is about 380 nm in size with negative charge rounded particles; while they enter into the acid environment (pH < 7), hydrogen ions (H+) trigger DOX release, their size becomes larger and the surface charge turns positive. These larger particles are rapidly disintegrated after exposure to NIR light and then the remaining DOX, IFNa1b, and ICG are released. In vivo, the IID with larger size and positive charge resulting from low pH is is easy to accumulate in tumor tissue. Tumors can be exposed to NIR light when needed to control the release of these three drugs. Hence, DOX, ICG, and IFNa1b can be enriched in the tumor to the high efficiency of combined chemotherapy, photothermal therapy, and immunotherapy. (c) 2023 Elsevier Inc. All rights reserved.

Automated summary

Programmed response, carrier-free, and multimodal therapy drug delivery systems (DDS) offer promising solutions to address multidirectional cytotoxic effects, inefficient antitumor effects, and severe side effects in cancer therapy. In this study, a carrier-free DDS called IFNa1b-ICG-DOX (IID) was developed using a one-step method without any additional reagents, combining interferon a1b (IFNa1b), indocyanine green (ICG), and doxorubicin (DOX). The system achieved smart and programmed drug delivery through stimuli-responsive controlled release triggered by low pH and near-infrared (NIR) light. In vivo, the larger size and positive charge of IID in low pH environments facilitated its accumulation in tumor tissue, and NIR light could be used to control the release of the drugs, enabling efficient combined chemotherapy, photothermal therapy, and immunotherapy.