Laser‐Triggered Small Interfering RNA Releasing Gold Nanoshells against Heat Shock Protein for Sensitized Photothermal Therapy

Abstract

The resistance of cancer cells to photothermal therapy is closely related to the overexpression of heat shock proteins (HSPs), which are abnormally upregulated when cells are under lethal stresses. Common strategies that use small molecule inhibitors against HSPs to enhance hyperthermia effect lack spatial and temporal control of drug release, leading to unavoidable systemic toxicity. Herein, a versatile photothermal platform is developed which is composed of a hollow gold nanoshell core densely packed with small interfering RNAs against heat shock protein 70 (Hsp70). Upon near infrared light irradiation, the small interfering RNAs can detach from gold surface specifically and escape from endosomes for Hsp70 silencing. Meanwhile, the temperature increases for hyperthermia therapy due to the high photothermal efficiency of the nanoshells. Efficient downregulation of Hsp70 after light activation is achieved in vitro and in vivo. Ultimately, the light‐controlled dual functional nanosystem, with the effects of Hsp70 silencing and temperature elevation, results in sensitized photothermal therapy in nude mice model under mild temperature. This strategy smartly combines the localized photothermal therapy with controlled Hsp70 silencing, and has great potential for clinical translation with a simple and easily controlled structure.

Deep Tumor Penetrating Bioparticulates Inspired Burst Intracellular Drug Release for Precision Chemo‐Phototherapy

“…For comparison, the Lipos and rHDL groups resulted in a temperature elevation to 38.31 and 40.43 °C. The irreversible tumor damage triggered by the temperature increase between 42 and 45 °C was attributed to hyperthermia‐induced cell death (PTT), including upregulation of the apoptotic gene expression levels, suppression of Tumor necrosis factor (TNF)‐α resistance, mitochondrial damage, and cell coagulative necrosis . Our results indicate that pHDL/PTX‐ICG possessed higher PTT efficiency among formulations, most likely because of the improved targetability and photostability of the encapsulated‐ICG in the aqueous solution derived from the nanoparticles encapsulation.…”

Nanoparticle‐based photothermal and photodynamic immunotherapy for tumor treatment

“…In terms of tumor therapy, to the best of our knowledge, PTT exerts antitumor effects mainly through direct thermal ablation (over 42 C). 31 33 Ali et al used quercetin, a HSP70 siRNA and HSP70 inhibitor, to enhance gold-nanorod-based PTT and achieved satisfactory results, that is, a potent cytotoxic effect on a wide range of tumor tissues at low laser power. [23][24][25] Therefore, tumor ablation can be improved by increasing the hyperthermia temperature, which researchers typically achieve by increasing the power of irradiation light or the concentration of photothermal agents.…”

“…32 HSP70 siRNA delivery through gold nanoshells designed by Wang et al can interfere with the expression of HSP70 and selectively sensitize the PTT efficacy on tumors with minimal side effects both in vitro and in vivo. 33 Ali et al used quercetin, a HSP70 siRNA and HSP70 inhibitor, to enhance gold-nanorod-based PTT and achieved satisfactory results, that is, a potent cytotoxic effect on a wide range of tumor tissues at low laser power. 34 The inhibition of HSP90 expression results in a compensatory increase in HSP70, which is detrimental to the improvement of PTT.…”

Engineered Cell‐Derived Microparticles Bi2Se3/DOX@MPs for Imaging Guided Synergistic Photothermal/Low‐Dose Chemotherapy of Cancer

“…[33][34][35][36] Combining with traditional method for tumor treatment, enhanced therapeutic effect can usually be reached by improved tumor targeting and synergistic effect of comprehensive therapy. [33][34][35][36] Combining with traditional method for tumor treatment, enhanced therapeutic effect can usually be reached by improved tumor targeting and synergistic effect of comprehensive therapy.…”