Intracellular Reduction-Responsive Molecular Targeted Nanomedicine for Hepatocellular Carcinoma Therapy

Abstract

The stimuli-responsive polymer-based platform for controlled drug delivery has gained increasing attention in treating hepatocellular carcinoma (HCC) owing to the fascinating biocompatibility and biodegradability, improved antitumor efficacy, and negligible side effects recently. Herein, a disulfide bond-contained polypeptide nanogel, methoxy poly(ethylene glycol)−poly(l-phenylalanine-co-l-cystine) [mPEG−P(LP-co-LC)] nanogel, which could be responsive to the intracellular reduction microenvironments, was developed to deliver lenvatinib (LEN), an inhibitor of multiple receptor tyrosine kinases, for HCC therapy. The lenvatinib-loaded nanogel (NG/LEN) displayed concise drug delivery under the stimulus of glutathione in the cancer cells. Furthermore, the intracellular reduction-responsive nanomedicine NG/LEN showed excellent antitumor effect and almost no side effects toward both subcutaneous and orthotopic HCC tumor-allografted mice in comparison to free drug. The excellent tumor-inhibition efficacy with negligible side effects demonstrated the potential of NG/LEN for clinical molecular targeted therapy of gastrointestinal carcinoma in the future.

Mapping research trends of transarterial chemoembolization for hepatocellular carcinoma from 2012 to 2021: A bibliometric analysis

“…Due to the method of medication, the targeting effect of TKIs is poor, while nanodelivery systems can provide an opportunity to overcome the drawbacks and achieve good results[ 34 ]. Ding et al [ 35 ] developed peptide nanogels with a stimulatory response for the delivery of lenvatinib with good tumor suppression and few side effects. Although some nanoparticles (NPs) have been approved by the FDA for clinical use, the safety of NPs has been an unavoidable issue during human applications.…”

Strategies and Recent Advances on Improving Efficient Antitumor of Lenvatinib Based on Nanoparticle Delivery System

“…In addition, irregular hepatic lobules structure also occurred, and some hepatocytes exhibited mild staining intensity and were slightly vacuolated. 47 These findings suggest that LVN-NDDS can reduce LVN toxicity on hematology and histology levels.…”

“…In terms of extra toxicity associated with NDDS, most studies found that LVN-NDDS had good biosafety profile and had negligible side effects compared with PBS. 36,39,40,43,[45][46][47][49][50][51][52]54 However, several studies reported that LVN-NDDS was primarily accumulated and distributed to the liver 36,42,43 and spleen 42 except for the tumor. Overall, these results demonstrate that LVN-NDDS can effectively kill cancer cells without causing significant toxicity.…”

Efficacy analysis of targeted nanodrug for non-small cell lung cancer therapy

“…The RGD peptide-modified nanogel called RGD−polyethylene glycol−poly (L-phenylalanine- co -L-cystine) (RGD−PEG−P (LP- co -LC; RGD-NP) and untargeted nanogel called methoxy polyethylene glycol−poly (L-phenylalanine- co -L-cystine) (mPEG−P (LP- co -LC; NP) were prepared by previous method ( Li et al, 2018 ; Ding et al, 2022 ), which were provided from the Changchun Institute of Applied Chemistry, Chinese Academy of Sciences. VCR.…”