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Deeply Infiltrating iRGD-Graphene Oxide for the Intensive Treatment of Metastatic Tumors through PTT-Mediated
Honglan Wang1, Jiyuan Zhou1, Ying Fu1
1Department of Pharmaceutics, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, 211198, China.
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.
Insights
This study introduces iRGD-modified graphene oxide (GO) nanosheets for enhanced chemotherapy delivery to metastatic tumors. This approach improves drug penetration and combines photothermal therapy to overcome tumor resistance and metastasis.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Limited tumor infiltration and low drug concentration hinder chemotherapy efficacy, promoting resistance and metastasis.
- Current treatments struggle with effective drug delivery to solid tumors, especially metastatic ones.
Purpose of the Study:
- To develop iRGD-modified graphene oxide (GO) nanosheets (IPHG) for intensive treatment of metastatic tumors.
- To utilize focused delivery, photothermal therapy (PTT)-mediated chemosensitization, and PTT-strengthened integrin targeting for antimigration.
Main Methods:
- Fabrication of iRGD-modified graphene oxide (GO) nanosheets (IPHG) loaded with doxorubicin (DOX).
- In vitro and in vivo evaluation of IPHG's tumor-selective infiltration, transendothelial and intratumoral transport.
- Application of near-infrared irradiation for photothermal therapy (PTT) in combination with chemotherapy.
Main Results:
- IPHG demonstrated tumor-selective infiltration due to its 2D structure and iRGD-mediated transport.
- PTT elevated drug concentration, leading to chemosensitization and significant tumor suppression.
- Synergistic effects of iRGD targeting and PTT impaired cell motility and metastasis by remodeling the cytoskeleton.
Conclusions:
- The developed IPHG system offers a promising drug delivery paradigm for combating tumor resistance and metastasis.
- Targeted delivery and combined PTT-chemotherapy overcome limitations of poor drug access in traditional chemotherapy.
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