In situ monitoring of doxorubicin release from biohybrid nanoparticles modified with antibody and cell-penetrating peptides in breast cancer cells using surface-enhanced Raman spectroscopy.
In situ monitoring of drug release in cancer cells is very important for real-time assessment of drug release dynamics in chemotherapy. In this study, we report label-free in situ monitoring and control of intracellular anti-cancer drug delivery process using biohybrid nanoparticles based on surface-enhanced Raman spectroscopy (SERS) for the first time. Each biohybrid nanoparticle consisted of gold nanoparticle, cell-penetrating peptide (Tat peptide), and cancer-targeting antibody to increase the efficacy of the anti-cancer drug delivery with specific targeting and increased uptake rate. The doxorubicin (Dox)-loaded biohybrid nanoparticles were showed specific SERS spectra of Dox, specifically immobilized on the target cell membrane and quickly penetrated into the cells when treated on the mixed cell culture condition. The intracellular release of Dox from the biohybrid nanoparticle was continuously monitored with time-dependent change of intracellular SERS signals of Dox. The releasing rate of Dox was successfully controlled with the addition of glutathione on the cells. The anti-cancer effect of intracellular released Dox was confirmed with cell viability assay. With the proposed monitoring system, specific cancer cell targeting and improved uptake of the anti-cancer drug were detected and time-dependent intracellular release of the anti-cancer drug was monitored successfully. The proposed novel in situ monitoring system can be used as a spectroscopic analysis tool for label-free monitoring of the time-dependent release of various kinds of anti-cancer drugs inside cells.
Interdisciplinary Program of Integrated Biotechnology, Sogang University, 121-742 Seoul, Republic of Korea.
Md Khaled
MK
Hossain
Department of Chemical and Biomolecular Engineering, Sogang University, 121-742 Seoul, Republic of Korea.
Hyeon-Yeol
HY
Cho
Department of Chemical and Biomolecular Engineering, Sogang University, 121-742 Seoul, Republic of Korea.
Kyeong-Jun
KJ
Kim
Interdisciplinary Program of Integrated Biotechnology, Sogang University, 121-742 Seoul, Republic of Korea; Department of Chemical and Biomolecular Engineering, Sogang University, 121-742 Seoul, Republic of Korea. Electronic address: jwchoi@sogang.ac.kr.
Jeong-Woo
JW
Choi
D000906:Antibodies / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000032:analysis; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000503:physiopathology; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000493:pharmacokinetics; D004058:Diffusion; D004317:Doxorubicin / Q000008:administration & dosage* / Q000032:analysis*; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D053761:Nanocomposites / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D013059:Spectrum Analysis, Raman / Q000379:methods*
D000906:Antibodies; D000970:Antineoplastic Agents; D057846:Cell-Penetrating Peptides; D053769:Nanocapsules; D004317:Doxorubicin
Cell-penetrating peptide; In situ monitoring; Intracellular release; Surface-enhanced Raman spectroscopy