Abstract
BackgroundNanoscale drug delivery systems have emerged as broadly applicable approach for chemo-photothermal therapy. However, these nanoscale drug delivery systems suffer from carrier-induced toxicity, uncontrolled drug release and low drug carrying capacity issues. Thus, to develop carrier-free nanoparticles self-assembled from amphiphilic drug molecules, containing photothermal agent and anticancer drug, are very attractive.ResultsIn this study, we conjugated camptothecin (CPT) with a photothermal agent new indocyanine green (IR820) via a redox-responsive disulfide linker. The resulting amphiphilic drug–drug conjugate (IR820-SS-CPT) can self-assemble into nanoparticles (IR820-SS-CPT NPs) in aqueous solution, thus remarkably improving the membrane permeability of IR820 and the aqueous solubility of CPT. The disulfide bond in the IR820-SS-CPT NPs could be cleaved in GSH rich tumor microenvironment, leading to the on demand release of the conjugated drug. Importantly, the IR820-SS-CPT NPs displayed an extremely high therapeutic agent loading efficiency (approaching 100%). Besides, in vitro experimental results indicated that IR820-SS-CPT NPs displayed remarkable tumor cell killing efficiency. Especially, the IR820-SS-CPT NPs exhibited excellent anti-tumor effects in vivo. Both in vitro and in vivo experiments were conducted, which have indicated that the design of IR820-SS-CPT NPs can provide an efficient nanotherapeutics for chemo-photothermal therapy.ConclusionA novel activatable amphiphilic small molecular prodrug IR820-SS-CPT has been developed in this study, which integrated multiple advantages of GSH-triggered drug release, high therapeutic agent content, and combined chemo-photothermal therapy into one drug delivery system.Graphical
Highlights
Nanoscale drug delivery systems have emerged as broadly applicable approach for chemo-photothermal therapy
A novel activatable amphiphilic small molecular prodrug IR820-SS-CPT has been developed in this study, which integrated multiple advantages of GSH-triggered drug release, high therapeutic agent content, and combined chemo-photothermal therapy into one drug delivery system
Synthesis and characterization of IR820‐SS‐CPT conjugate As depicted in Scheme 2, the theranostic prodrug IR820-SS-CPT was synthesized through a four-step process
Summary
Nanoscale drug delivery systems have emerged as broadly applicable approach for chemo-photothermal therapy. Chemotherapy itself has many disadvantages in clinical practice, such as poor therapeutic efficacy, systemic toxicity, and drug resistance [5, 6] To address these issues, there has been a great interest in building synergistic drug delivery systems capable of co-delivery of two or more therapeutic agents to achieve synergistic therapeutic effect for battling the tumor heterogeneity [7, 8]. There has been a great interest in building synergistic drug delivery systems capable of co-delivery of two or more therapeutic agents to achieve synergistic therapeutic effect for battling the tumor heterogeneity [7, 8] These strategies may take advantage of different treatments to remarkably augment the anti-tumor effect, but can overcome serious adverse effects [9, 10]. Many nanoscale drug delivery systems have been constructed for the co-delivery of photothermal agents and chemotherapeutic agents for synergistic cancer therapy [21]
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