Tumor-triggered drug release from calcium carbonate-encapsulated gold nanostars for near-infrared photodynamic/photothermal combination antitumor therapy

Abstract

Different stimulus including pH, light and temperature have been used for controlled drug release to prevent drug inactivation and minimize side-effects. Herein a novel nano-platform (GNS@CaCO3/ICG) consisting of calcium carbonate-encapsulated gold nanostars loaded with ICG was established to couple the photothermal properties of gold nanostars (GNSs) and the photodynamic properties of indocyanine green (ICG) in the photodynamic/photothermal combination therapy (PDT/PTT). In this study, the calcium carbonate worked not only a drug keeper to entrap ICG on the surface of GNSs in the form of a stable aggregate which was protected from blood clearance, but also as the a pH-responder to achieve highly effective tumor-triggered drug release locally. The application of GNS@CaCO3/ICG for in vitro and in vivo therapy achieved the combined antitumor effects upon the NIR irradiation, which was superior to the single PDT or PTT. Meanwhile, the distinct pH-triggered drug release performance of GNS@CaCO3/ICG implemented the tumor-targeted NIR fluorescence imaging. In addition, we monitored the bio-distribution and excretion pathway of GNS@CaCO3/ICG based on the NIR fluorescence from ICG and two-photon fluorescence and photoacoustic signal from GNSs, and the results proved that GNS@CaCO3/ICG had a great ability for tumor-specific and tumor-triggered drug release. We therefore conclude that the GNS@CaCO3/ICG holds great promise for clinical applications in anti-tumor therapy with tumor imaging or drug tracing.

Water‐Responsive Hybrid Nanoparticles Codelivering ICG and DOX Effectively Treat Breast Cancer via Hyperthermia‐aided DOX Functionality and Drug Penetration

“…One reason is insufficient drug release that involves a high local accumulation of DDSs that cannot convert into effective drug levels in the target sites. This calls for a new and effective approach that improves drug release in cancer cells in response to certain continuous stimuli . In addition, the poor tumor penetration of DDSs is another cause for their disappointing therapeutic efficacy.…”

Engineering Targeting Materials for Therapeutic Cancer Vaccines

“…Another option to induce aggregation or release would be to have acid-labile amide bond breakage (Wu et al, 2018). Such strategies have been used to deliver chemotherapy (Yang et al, 2017), thermal therapy (Liu et al, 2017) or for tumor imaging (Hoffmann et al, 2012).…”

Photothermal effect by NIR-responsive excretable ultrasmall-in-nano architectures

“…2 Commonly, NPs that exhibit LSPRs at near-infrared (NIR) frequencies are gold anisotropic structures, which include nanostars and nanorods. [2][3][4][5] Noticeably, also gold nanoshells have emerged as an excellent photothermal transducer, as their NIR optical response can be easily tuned by adjusting the diameter-to-shell thickness ratio. 6 However, despite the excellent light-to-heat conversion performances demonstrated by these nanoplatforms, only nanoshells have reached clinical trial evaluation, whereas nanorods and nanostars are still confined to the preclinical stage.…”