Abstract
Background
Phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT), is a promising noninvasive strategy in the treatment of cancers due to its highly localized specificity to tumors and minimal side effects to normal tissues. However, single phototherapy often causes tumor recurrence which hinders its clinical applications. Therefore, developing a NIR-guided dendritic nanoplatform for improving the phototherapy effect and reducing the recurrence of tumors by synergistic chemotherapy and phototherapy is essential.
Methods
A fluorescent targeting ligand, insisting of ICG derivative cypate and a tumor penetration peptide iRGD (CRGDKGPDC), was covalently combined with PAMAM dendrimer to prepare a single agent-based dendritic theranostic nanoplatform iRGD-cypate-PAMAM-DTX (RCPD).
Results
Compared with free cypate, the resulted RCPD could generate enhanced singlet oxygen species while maintaining its fluorescence intensity and heat generation ability when subjected to NIR irradiation. Furthermore, our in vitro and in vivo therapeutic studies demonstrated that compared with phototherapy or chemotherapy alone, the combinatorial chemo-photo treatment of RCPD with the local exposure of NIR light can significantly improve anti-tumor efficiency and reduce the risk of recurrence of tumors.
Conclusion
The multifunctional theranostic platform (RCPD) could be used as a promising method for NIR fluorescence image-guided combinatorial treatment of tumor cancers.
Acknowledgments
This work was financially supported by the National Natural Science Foundation of China (No. 81673360 and 81601591), Shandong Provincial Natural Science Foundation (No. ZR2016HM45, ZR2017BH006 and ZR2016HB15), China Postdoctoral Natural Science Foundation (2017M612210), and Scientific Research Foundation for Youth Scholars from Qingdao University (No. 41117010026). The authors would like to thank Mr. Qingming Ma for his writing assistance.
Abbreviation list
iRG, DCRGDKGPDC; DTX, Docetaxel; PAMAM, polyamindoamine; CP, Cypate-PAMAM; RCP, iRGD-cypate-PAMAM; RCPD, iRGD-Cypate-PAMAM-DTX; DMF N, N-Dimcthylformamide; EDCI, 1-ethyl-3-(3ʹ-dimethylaminopropyl) carbodiimide; NHS, N-hydroxysuccinimide; DPBF, 1, 3-Diphenylisobenzofuran; FBS, Fetal bovine serum; DLS, Dynamic light scattering; TEM, Transmission electron microscopy; DCFH-DA, 2′,7′-dichlorofluorescin diacetate; MTT, Methyl thiazolyltetrazolium.
Disclosure
The authors report no conflicts of interest in this work.