Self‐Assembled/Drug‐Composed Nanomedicine for Synergistic Photonic Hyperthermia and Targeted Therapy of Breast Cancer by Inhibiting ERK, AKT, and STAT3 Signaling Cascades

Abstract

Superior to chemotherapy, photonic hyperthermia and targeted therapy have made attractive impacts on cancer treatment by virtue of their profound advantages such as high specificity and minimal invasiveness, but the rational integration of corresponding therapeutic drugs for achieving concurrent photothermal ablation/targeted therapy is still challenging. Herein, a self‐assembled nanomedicine Anlotinib@IR820 is constructed with drug formulations for highly efficient and synergistic photonic hyperthermia and targeted therapy against breast cancer. Specifically, the constructed Anlotinib@IR820 nanomedicine presents high accumulation at the tumor site owing to the enhanced permeability and retention effect and simultaneously overcomes the obstacles of poor water solubility of Anlotinib (for targeted therapy) and the short lifetime of IR820 (for photonic ablation). The photothermal ablation as activated by near‐infrared laser can not only irradiate cancer cells but also promote the cellular uptake of Anlotinib, which presents a profound synergistic function both in vitro and in vivo. Mechanically, Anlotinib@IR820 nanomedicine can induce apoptosis and cause cell cycle arrest in breast cancer through inhibiting ERK, AKT, and STAT3 pathways. Therefore, the rationally designed drug‐composed Anlotinib@IR820 nanomedicine exhibits high clinical translation potential because of its therapeutic nanoformulation, which provides an alternative option for efficient combinational therapy of breast cancer.

Multi-target tyrosine kinase inhibitor nanoparticle delivery systems for cancer therapy

“… Nanoparticles Combination Therapy Cell Lines Cell Viability Rate (%) Treatment Conditions Method Ref. Anlotinib@IR820 PTT MCF7 33 24 ​h([Anlotinib] ​= ​0.8 ​ppm, [IR820] ​= ​5 ​ppm, 808 ​nm, 0.8 ​W cm −2 , 3min) CCK8 [ 87 ] Lip-IR780-Sunitinib PTT 4T1 50 24 ​h([IR780] ​= ​0.2 ​μg/mL, 808 ​nm, 1 ​W cm −2 , 4min) MTT [ 29 ] MoS 2 -PEG-Er/DOX PTT A549 6.1 24 ​h([MoS 2 -PEG] ​= ​180 ​μg/mL,[Erlotinib] ​= ​10 ​μg/mL, [DOX] ​= ​20 ​μg/mL, 808 ​nm, 1 ​W cm −2 , 10min) MTT [ 182 ] HPGBCA PDT A549 50 48 ​h([HPGBCA] ​= ​0.41 ​mM, 660 ​nm, 50 ​mW ​cm −2 , 10min) MTT [ 183 ] (ICG ​+ ​S)@mSiO 2 PDT, Immunotherapy H22 1 24 ​h([ICG] ​= ​0.012 ​mg ​mL −1 , [Sorafenib] ​= ​0.08 ​mg ​mL −1 S or [(ICG ​+ ​S)@mSiO 2 ] ​= ​0.1 ​mg ​mL −1 ) MTT [ 184 ] NanoMnSor Immunotherapy JHH-7 ≈30 72 ​h([sorafenib] ​= ​4 ​μM,[MnO 2 ] ​= ​40 ​μM, hypoxic ​= ​1% O 2 ) MTT [ 179 ] SEHPA Gene therapy Huh-7 ≈25 24 ​h([sorafenib] ​= ​8 ​μg/mL) MTT [ 185 ] SF-PL/siGPC3 Gene therapy Hep-G2 36.6 48 ​h([sorafenib] ​= ​4 ​μM) CCK8 [ 186 ] EPC …”

“…9 b). Anlotinib@IR820 nanomedicine can induce apoptosis and cell cycle blockade via targeting ERK, AKT, and STAT3 signal transduction pathways, to inhibit the growth of breast cancer [ 87 ]. MoS 2 is a two-dimensional transition metal dichalcogenide photothermal agent, and it is evidenced to have a higher loading ratio than that of graphene oxide in a research report [ 192 ].…”

Assembled small organic molecules for photodynamic therapy and photothermal therapy

“…Both in vitro and in vivo experiments systematically demonstrated that NIR-activated photothermal effect not only irradiated tumor directly but promoted the release and uptake of anlotinib, which strengthened the therapeutic efficacy synergistically. 79 …”

“…A) The co-assembly of anlotinib with NIR dye IR820 forms nanoparticles anlotinib@IR820 for synergistic PTT and targeted chemotherapy; (this figure has been reproduced from ref 79. with permission from WILEY-VCH).…”

“…with permission from WILEY-VCH). (B and C) Under laser irradiation at 808 nm (B) or mild heating (C) the photothermal-conversion and the disassembly of anlotinib@IR820 can be achieved, which induce the enhanced drug delivery 79 (this figure has been reproduced from ref 79. with permission from WILEY-VCH).…”