Investigation of squalene-doxorubicin distribution and interactions within single cancer cell using Raman microspectroscopy

Rammal, Hassan; Assaad, Almar Al; Dosio, Franco; Stella, Barbara; Maksimenko, Andrei; Mura, Simona; Gulick, Laurence Van; Callewaert, Maïté; Desmaële, Didier; Couvreur, Patrick; Morjani, Hamid; Beljebbar, A.

doi:10.1016/j.nano.2021.102404

Cited by 12 publications

(9 citation statements)

References 53 publications

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“…Based on the EPR effect, many nanomedicines have been developed, including polymer conjugates, polymeric micelles, liposome, nanoparticles, antibody drug conjugate, and so on, some of which are approved for clinical use, and more are in preclinical trials [ 25 ]. For example, recently squalene that is a triterpene in the cholesterol biosynthesis pathway widely distributed in nature, has been successfully developed as a nanoplatform for various therapeutic molecules and nucleoside analogues with gemcitabine, as well as doxorubicin and paclitaxel, and the the squalenoylated doxorubicin nanoassemblies exhibited much improved anticancer therapeutic efficacy with decreased cytotoxicity [ 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of Tumor Targeted-Anthracycline Nanomedicine, HPMA Copolymer-Conjugated Pirarubicin (P-THP) against Gynecological Malignancies

Yanazume

Fang

Islam

et al. 2022

JPM

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Anthracyclines are important for the treatment of gynecological malignancies, but their effects are modest, and one of the major reasons is the lack of a tumor-targeting property. To overcome this drawback, a poly (hydroxypropyl meta-acrylamide) conjugated with tetrahydropyraryl doxorubicin (P-THP) has been developed, which exhibits a highly tumor-specific accumulation owing to the enhanced permeability and retention effect. The effect of P-THP has been confirmed by using various cell lines and solid tumor models, while its effect on gynecological malignancies have not been investigated. In this regard, human uterine sarcoma cell line with metastatic potential MEA-SA C9 high, epithelial ovarian cancer cell line A2780 and its cisplatin-resistant line A2780cis, and DOX-resistant line A2780ADR were used in this study, and the therapeutic effect as well as the safety profiles of P-THP were investigated compared to native THP, cisplatin, and paclitaxel, which are commonly used for gynecological malignancies, both in vitro and in vivo. Similar to native THP, a dose-dependent toxicity of P-THP was identified in all cell lines. Moreover, the IC50 values in the 3 h following P-THP were 1.5–10 times higher than those at 72 h, though the intracellular uptake of P-THP in all cells were 2–10-fold less than THP. In vivo studies using xenograft tumor models revealed that P-THP significantly suppressed the MES-SA C9 high, A2780, and A2780cis tumor growth at the dose of 15 mg/kg (THP equivalent), which is three times above the maximal tolerance dose of native THP, while no body weight loss or acute death occurred. However, in A2780ADR cells and the xenograft model, no significant difference in the therapeutic effect was observed between THP and P-THP, suggesting that P-THP exhibits its effect depending on the release of the active free THP in tumor tissues, and thus the internalization into tumor cells. These findings indicates that P-THP has the potential as a therapeutic for gynecological malignancies to improve the therapeutic outcomes and survival rates of patients, even in refractory patients.

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Section: Discussionmentioning

confidence: 99%

Effect of Tumor Targeted-Anthracycline Nanomedicine, HPMA Copolymer-Conjugated Pirarubicin (P-THP) against Gynecological Malignancies

Yanazume

Fang

Islam

et al. 2022

JPM

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“…148 Rammal et al observed the distribution of doxorubicin (DOX) and its squalenoylated nanoparticles in cancer cells using Raman marker bands, 1211 and 1241 cm −1 , in the fingerprint region. 155 In addition, Fu et al described SRS imaging and quantification of TKIs imatinib and nilotinib using Raman peaks ∼1300 cm −1 ; in addition, the process of drug uptake into lysosomes was monitored simultaneously using TPEF. 156 Dong et al also employed polarization-sensitive SRS from CC stretching vibration in the fingerprint region of amphotericin B (AmB), an antifungal agent, to monitor its distribution in fungal cells.…”

Section: ■ Raman Spectroscopy For Diagnosticsmentioning

confidence: 99%

Diagnostics and Therapy Assessment Using Label-Free Raman Imaging

El-Mashtoly

Gerwert

2021

Anal. Chem.

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“…The potential of confocal Raman microspectroscopy as a label-free and non-destructive tool for molecular characterization of anticancer nanodrugs and their potential toxic effects on cells, was studied by Rammal and co-workers [ 51 ]. They investigated the activity of the anticancer chemotherapeutic drug doxorubicin within single murine lung carcinoma cells and human breast cancer cells.…”

Section: Spontaneous Raman Scatteringmentioning

confidence: 99%

Current and Future Advancements of Raman Spectroscopy Techniques in Cancer Nanomedicine

Canetta

2021

IJMS

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Raman scattering is one of the most used spectroscopy and imaging techniques in cancer nanomedicine due to its high spatial resolution, high chemical specificity, and multiplexity modalities. The flexibility of Raman techniques has led, in the past few years, to the rapid development of Raman spectroscopy and imaging for nanodiagnostics, nanotherapy, and nanotheranostics. This review focuses on the applications of spontaneous Raman spectroscopy and bioimaging to cancer nanotheranostics and their coupling to a variety of diagnostic/therapy methods to create nanoparticle-free theranostic systems for cancer diagnostics and therapy. Recent implementations of confocal Raman spectroscopy that led to the development of platforms for monitoring the therapeutic effects of anticancer drugs in vitro and in vivo are also reviewed. Another Raman technique that is largely employed in cancer nanomedicine, due to its ability to enhance the Raman signal, is surface-enhanced Raman spectroscopy (SERS). This review also explores the applications of the different types of SERS, such as SERRS and SORS, to cancer diagnosis through SERS nanoprobes and the detection of small-size biomarkers, such as exosomes. SERS cancer immunotherapy and immuno-SERS (iSERS) microscopy are reviewed.

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Investigation of squalene-doxorubicin distribution and interactions within single cancer cell using Raman microspectroscopy

Abstract: Investigation of squalene-doxorubicin distribution and interactions within single cancer cell using Raman microspectroscopy

Cited by 12 publications

References 53 publications

Effect of Tumor Targeted-Anthracycline Nanomedicine, HPMA Copolymer-Conjugated Pirarubicin (P-THP) against Gynecological Malignancies

Effect of Tumor Targeted-Anthracycline Nanomedicine, HPMA Copolymer-Conjugated Pirarubicin (P-THP) against Gynecological Malignancies

Diagnostics and Therapy Assessment Using Label-Free Raman Imaging

Current and Future Advancements of Raman Spectroscopy Techniques in Cancer Nanomedicine

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