Intratumoral injection of anlotinib hydrogel enhances antitumor effects and reduces toxicity in mouse model of lung cancer

Abstract

This study was conducted to determine the antitumor effects and ability of an anlotinib (AL) hydrogel (AL–HA–Tyr) to reduce toxicity in a mouse model of Lewis lung cancer (LLC). We constructed a drug carrier system for AL, verified its effectiveness and systemic safety, and provided a preliminary experimental foundation for clinical carrier transformation. AL–HA–Tyr was prepared by encapsulating AL with hyaluronic acid–tyramine (HA–Tyr) conjugates. Colony and tube formation assays showed that AL–HA–Tyr restrained the proliferation of human umbilical vein endothelial cells (HUVECs) and LLC cells, respectively, in vitro , and that AL exerted significant anti-angiogenesis and anti-tumor effects. The invasion and migration of HUVECs and LLC cells were efficiently suppressed by AL according to transwell assays. HUVEC and LLC cell-cycle and apoptosis analysis clarified the direct anti-tumor effects of AL–HA–Tyr. Mice engrafted with LLC cells in vivo were administered oral saline, oral AL, or an intratumoral injection of HA–Tyr or AL–HA–Tyr. The results showed that AL–HA–Tyr obviously reduced visceral toxicity and decreased Ki67 and VEGF-A expression in tumor cells compared with AL. Furthermore, AL–HA–Tyr significantly prolonged the survival of tumor-bearing mice. Overall, AL–HA–Tyr enhanced antitumor effects and reduced toxicity in the LLC model. It provided a foundation for the clinical transformation of drug carrier systems.

Tumor-Acidity Responsive Polymeric Nanoparticles for Targeting Delivery of Angiogenesis Inhibitor for Enhanced Antitumor Efficacy With Decreased Toxicity

“…In each time point, 1 ml of PBS outside the lysis bag was taken out and 1 ml of fresh PBS at corresponding pH value was added. Finally, the amount of Anlotinib hydrochloride in the 1 ml of PBS was determined by High Performance Liquid Chromatography at 220 nm based on the previous report ( Gao et al, 2020 ). Then, the accumulated drug release was calculated.…”

A novel tubulin inhibitor, 6h, suppresses tumor-associated angiogenesis and shows potent antitumor activity against non–small cell lung cancers

“…NSCLC is a solid tumor that is highly vascularized. Studies have shown that the growth and metastasis of solid tumors are supported by angiogenesis ( 7 , 8 ). It is known that tubulin inhibitors are the main drugs for the treatment of NSCLC, with the effect of altering microtubule dynamics and inhibiting angiogenesis ( 9 ).…”

Intratumoral Treatment with Chemotherapy and Immunotherapy for NSCLC with EBUS-TBNA 19G

“…The same has been observed with radiotherapy 35 - 37 . With local intratumoral therapy less adverse effects have been observed 38 , 39 . Moreover; the issue method of administration, should be easy for the patient and without complication.…”