A Smart Multifunctional Nanoparticle for Enhanced Near-Infrared Image-Guided Photothermal Therapy Against Gastric Cancer

Abstract

Background Surgery is considered to be a potentially curative approach for gastric cancer. However, most cases are diagnosed at a very advanced stage for the lack of typical symptoms in the initial stage, which makes it difficult to completely surgical resect of tumors. Early diagnosis and precise personalized intervention are urgent issues to be solved for improving the prognosis of gastric cancer. Herein, we developed an RGD-modified ROS-responsive multifunctional nanosystem for near-infrared (NIR) imaging and photothermal therapy (PTT) against gastric cancer. Methods Firstly, the amphiphilic polymer was synthesized by bromination reaction and nucleophilic substitution reaction of carboxymethyl chitosan (CMCh) and 4-hydroxymethyl-pinacol phenylborate (BAPE). Then, it was used to encapsulate indocyanine green (ICG) and modified with RGD to form a smart multifunctional nanoparticle targeted to gastric cancer (CMCh-BAPE-RGD@ICG). The characteristics were determined, and the targeting capacity and biosafety were evaluated both in vitro and in vivo. Furthermore, CMCh-BAPE-RGD@ICG mediated photothermal therapy (PTT) effect was studied using gastric cancer cells (SGC7901) and SGC7901 tumor model. Results The nanoparticle exhibited suitable size (≈ 120 nm), improved aqueous stability, ROS-responsive drug release, excellent photothermal conversion efficiency, enhanced cellular uptake, and targeting capacity to tumors. Remarkably, in vivo studies suggested that CMCh-BAPE-RGD@ICG could accurately illustrate the location and margin of the SGC7901 tumor through NIR imaging in comparison with non-targeted nanoparticles. Moreover, the antitumor activity of CMCh-BAPE-RGD@ICG-mediated PTT could effectively suppress tumor growth by inducing necrosis and apoptosis in cancer cells. Additionally, CMCh-BAPE-RGD@ICG demonstrated excellent biosafety both in vitro and in vivo. Conclusion Overall, our study provides a biocompatible theranostic nanoparticle with enhanced tumor-targeting ability and accumulation to realize NIR image-guided PTT in gastric cancer.

Versatile and Robust Method for Antibody Conjugation to Nanoparticles with High Targeting Efficiency

“…This low internalization could be explained by the non-specificity of this antibody to membrane proteins in these cell lines and the negative zeta potential (−11.8 mV) of the resulting IgG-conjugated nanoparticles (which minimized their non-specific uptake). To assure that the observed increase in cellular uptake in CD44overexpressing cells was not linked to the specific cell lines used, we checked the uptake of αCD44-PEI-MSNPs in two fibroblast cell lines, NIH3T3 (mouse embryonic fibroblasts with a low CD44 expression [78,79]) and BJ1-hTERT (human fibroblasts with high CD44 expression [80,81]), using the same experimental approach (Figure S4). The respective CD44 expression in the two cell lines was validated with a standard immunofluorescence staining of CD44 (Figure S5, Supplementary Materials).…”

Polymer encapsulated clinical ICG nanoparticles for enhanced photothermal therapy and NIR fluorescence imaging in cervical cancer

“…The loading efficiency (LE) of ICG were further studied, which was calculated via UV vis spectrophotometric method. 28 The loaded ICG dose in ICG@PSMA NPs was determined by the absorption value. The calculation formula was as follows: 28 …”

“… 28 The loaded ICG dose in ICG@PSMA NPs was determined by the absorption value. The calculation formula was as follows: 28 …”

Polymer-Based Nanosystems—A Versatile Delivery Approach

“…Specifically, stimuliresponsive delivery systems have been created to target the acidic pH and/or hypoxic environment characteristic of tumor cells [210] (Figure 5). In this respect, polymeric nanoparticles have been investigated as carriers towards various tumor cells, including breast [44,[211][212][213], colon [91,[214][215][216][217], gastric [169,[218][219][220], liver [116,221,222], bladder [46,223], skin [224,225], lung [36,92,226], prostate [94,[227][228][229], and ovarian [230][231][232] cancer cells (Table 2). In this respect, polymeric nanoparticles have been investigated as carriers towards various tumor cells, including breast [44,[211][212][213], colon [91,[214][215][216][217], gastric [169,[218]…”

“…Another promising strategy is to deliver conventional contrast agents by polymerbased vehicles. In this respect, Shao et al [220] have proposed a carboxymethyl chitosan 4-hydroxymethyl-pinacol phenyl borate carrier encapsulated with indocyanine green and modified with RGD. Their ROS-responsive nanosystem can be employed in near-infrared imaging and photothermal therapy against gastric cancer.…”