Deeply Infiltrating iRGD‐Graphene Oxide for the Intensive Treatment of Metastatic Tumors through PTT‐Mediated Chemosensitization and Strengthened Integrin Targeting‐Based Antimigration

Abstract

A limited infiltration and the subsequent low effective drug concentration result in poor chemotherapeutic outcomes against tumors, and even further promote tumor resistance and metastatic. Herein, iRGD‐modified graphene oxide (GO) nanosheets (IPHG) are developed for the intensive treatment of metastatic tumors using focus‐specific penetrated delivery together with photothermal therapy‐mediated chemosensitization and photothermal therapy‐strengthened integrin targeting‐based antimigration. In vitro and in vivo data verified the mechanism of the tumor‐selective infiltration of IPHG is based on a rigid 2D structure‐associated advantage regarding hemodynamics and endothelial contact, followed by iRGD‐endowed transendothelial and intratumoral transport. Once IPHG‐DOX‐penetrated 4T1 tumors are exposed to near‐infrared irradiation, hyperthermia stress and photothermal therapy‐elevated effective drug concentrations result in chemosensitization and prominent tumor suppression. Meanwhile, the specific binding of iRGD to integrins and photothermal therapy leads to the synergistic perturbation of cytoskeleton remodeling and subsequent impairment of cell motility and metastasis. The tailored design of IPHG validates a promising paradigm for drug delivery to combat tumor resistance and metastasis resulting from poor target access for single chemotherapy.

The Microstructure, Antibacterial and Antitumor Activities of Chitosan Oligosaccharides and Derivatives

“…It has been reported that COS lactate (COL) has great potential for tumor imaging due to its highly efficient intracellular and site-specific delivery [79,80]. Photothermal therapy (PTT) has great potential in tumor therapy because of its low toxicity to normal tissues and high tumor ablation efficiency [81][82][83]. Sungsu Lee et al [84] reported a study on the tumor targeting property of COL and the advantages of PTT, combining COL with nearinfrared (NIR) fluorescent group ZW800-1 to form a COL-ZW800-1 (Figure 9a) conjugate for targeted cancer imaging and PTT in cancer treatment.…”

NIR-Triggered and ROS-Boosted Nanoplatform for Enhanced Chemo/PDT/PTT Synergistic Therapy of Sorafenib in Hepatocellular Carcinoma

“…Recently, combination therapy that integrate chemotherapy with other therapeutic modalities have exhibited competitive advantages in overcoming chemoresistance [17][18][19]. Photodynamic therapy (PDT), a noninvasive treatment modality that uses photosensitizers and light to generate cytotoxic molecular species such as ROS to induce cell death, has received widespread attention in drug-resistant cancer treatment.…”

Nanoarchitectured Graphene Organic Framework for Drug Delivery and Chemo-photothermal Synergistic Therapy

“…More importantly, GO has excellent photothermal conversion performance and has become a favourable candidate for photothermal-chemotherapy synergistic treatment. 24,25…”

“…More importantly, GO has excellent photothermal conversion performance and has become a favourable candidate for photothermal-chemotherapy synergistic treatment. 24,25 Graphene organic framework (GOF) is a new type of GO-based porous framework material formed by interconnecting multilayer GO sheets and organic ligands. Its structure and performance can be designed by controlling the type, length and concentration of organic ligands.…”